JMIR Publications

JMIR Research Protocols

Ongoing Trials, Grant Proposals, Formative Research, Methods, Early Results


Journal Description


JMIR Research Protocols (ISSN 1929-0748) publishes peer-reviewed, openly accessible research ideas and grant proposals, study and trial protocols, reports of ongoing research, current methods and approaches, and preliminary results from pilot studies or formative research informing the design of medical and health-related research and technology innovations.

JMIR Res Protoc is a new journal spin-off of JMIR, the worlds' leading medical journal in health sciences / health services research and health informatics (Impact Factor 2015: 4.532)

JMIR Res Protoc publishes protocols and grant proposals in all areas of medicine (and their peer-review reports, if available), as well as feasibility studies, early reports and formative/process evaluations of ongoing studies and descriptions of the development and pilot evaluations of innovations and software applications or other interventions

JMIR Res Protoc is fully open access, with full text articles deposited in PubMed Central

Publishing research protocols, grant proposals, pilot/feasibility studies and early reports of ongoing and planned work encourages collaboration and early feedback, and reduces duplication of effort 

JMIR Res Protoc will be a valuable ressource for researchers who want to learn about current research methodologies and how to write a winning grant proposal

JMIR Res Protoc creates an early scientific record for researchers who have developed novel methodologies, software, innovations or elaborate protocols

JMIR Res Protoc faciliates subsequent publication of results demonstrating that the methodology has already been reviewed, and reduces the effort of writing up the results, as the protocol can be easily referenced

JMIR Res Protoc demonstrates to reviewers of subsequent results papers that authors followed and adhered to carefully developed and described a-priori methods

Studies whose protocols or grant proposal have been accepted in JMIR Res Protoc are "in principle accepted" for subsequent publication of results in other JMIR journals as long as authors adhere to their original protocol - regardless of study results (even if they are negative), reducing publication bias in medicine

Authors publishing their protocols in JMIR Res Protoc will receive a 20% discount on the article processing fee if they publish their results in another journal of the JMIR journal family (for example, JMIR for ehealth studies, i-JMR for others)


Recent Articles:

  • Genetic study in Iran. Image created by the authors. Licensed under Creative Commons Attribution 2.0.

    Rationale and Design of a Genetic Study on Cardiometabolic Risk Factors: Protocol for the Tehran Cardiometabolic Genetic Study (TCGS)


    Background: Cardiometabolic risk factors comprise cardiovascular diseases and/or diabetes, and need to be evaluated in different fields. Objective: The primary aim of the Tehran Cardiometabolic Genetic Study (TCGS) is to create a comprehensive genome-wide database of at least 16,000 Tehranians, who are participants of the ongoing Tehran Lipid and Glucose Study (TLGS) cohort. Methods: TCGS was designed in collaboration with the Research Institute for Endocrine Sciences and the genetic company deCODE. Participants had already been followed for over a 20-year period for major cardiometabolic-related health events including myocardial infarction, stroke, diabetes mellitus, hypertension, obesity, hyperlipidemia, and familial hypercholesterolemia. Results: The TCGS cohort described here comprises 17,186 (86.3%) of the 19,905 TLGS participants who provided a baseline blood sample that was adequate for plasma and deoxyribonucleic acid analysis. This study is comprised of 849 individuals and 3109 families with at least one member having genotype information. Finally, 5977 males and 7422 females with the total genotyping rate of 0.9854 were genotyped with HumanOmniExpress-24-v1-0 bead chips (containing 649,932 single-nucleotide polymorphism loci with an average mean distance of 4 kilobases). Conclusions: Investigations conducted within the TCGS will seek to identify relevant patterns of genetic polymorphisms that could be related to cardiometabolic risk factors in participants from Tehran. By linking genome-wide data to the existing databank of TLGS participants, which includes comprehensive behavioral, biochemical, and clinical data on each participant since cohort inception in 1999, the TCGS will also allow exploration of gene-gene and gene-environment interactions as they relate to disease status.

  • Air pollution and Pregnancy.  Image Source: Copyright Arash Hossein-Nezhad, please cite as

    Epigenetic Alterations and Exposure to Air Pollutants: Protocol for a Birth Cohort Study to Evaluate the Association Between Adverse Birth Outcomes and...


    Background: Prenatal exposure to air pollutants can increase the risk of adverse birth outcomes and susceptibility to a number of complex disorders later in life. Despite this general understanding, the molecular and cellular responses to air pollution exposure during early life are not completely clear. Objective: The aims of this study are to test the association between air pollution and adverse pregnancy outcomes, and to determine whether the levels of maternal and cord blood and of placental DNA methylation during pregnancy predict adverse birth outcomes in polluted areas. Methods: This is a birth cohort study. We will enroll pregnant healthy women attending prenatal care clinics in Tehran, Iran, who are resident in selected polluted and unpolluted regions before the 14th week of pregnancy. We will calculate the regional background levels of fine particulate matter (particles with a diameter between 2.5 and 10 μm) and nitrogen dioxide for all regions of by using data from the Tehran Air Quality Control Company. Then, we will select 2 regions as the polluted and unpolluted areas of interest. Healthy mothers living in the selected polluted and non polluted regions will be enrolled in this study. A maternal health history questionnaire will be completed at each trimester. During the first and second trimester, we will draw mothers’ blood for biochemical and DNA methylation analyses. At the time of delivery time, we will collect maternal and cord blood for biochemical, gene expression, and DNA methylation analyses. We will also record birth outcomes (the newborn’s sex, birth date, birth weight and length, gestational age, Apgar score, and level of neonatal care required). Results: The project was funded in March 2016 and enrollment will be completed in August 2017. Data analysis is under way, and the first results are expected to be submitted for publication in November 2017. Conclusions: We supposed that prenatal exposures to air pollutants can influence fetal reprogramming by epigenetic modifications such as DNA methylation. This could explain the association between air pollution and adverse pregnancy outcomes.

  • Drs. Kent and Fernandes-Taylor demonstrate the application with a patient. Image source: The authors. Photographer was Chris Frazee from Media Solutions in the Health Sciences Learning Center at the UW medical school. The Department of Surgery paid for and owns all rights.

    Feasibility of Implementing a Patient-Centered Postoperative Wound Monitoring Program Using Smartphone Images: A Pilot Protocol


    Background: Surgical site infections (SSI) represent a significant public health problem as the most common nosocomial infection and a leading cause of unplanned hospital readmissions among surgical patients. Many develop following hospital discharge and often go unrecognized by patients. Telemedicine offers the opportunity to leverage the mobile technology to remotely monitor wound recovery in the transitional period between hospital discharge and routine clinic follow-up. However, many existing telemedicine platforms are episodic, replacing routine follow-up, rather than equipped for continued monitoring; they include only low-risk patient populations and those who already have access to and comfort with the necessary technology; and transmit no visual information. Objective: Drawing upon the Coleman model for care transitions and the Proctor model for implementation, we propose a protocol of postoperative wound monitoring using smartphone digital images. In this study, we will establish the feasibility of such a program, both for patients and for the clinical care team. Methods: We will recruit 40 patients or patient/caregiver pairs from our inpatient vascular surgery service. Eligible patients will be English-speaking, 18 years of age or older, and have an incision at least 3 cm in length. Participants will receive a training session, during which they will learn to use the device and the wound monitoring smartphone app. Following hospital discharge, they will submit digital images of their wound and responses to a survey about their recovery for 14 days. Experienced health care providers on the vascular surgery inpatient service will review transmitted data daily and contact patients for any concerning findings. Results: Primary outcomes will include participant adherence to the protocol, time required for providers to review submissions, time from submission to provider review, and participant satisfaction. Secondary outcomes will include SSI detection and hospital readmission. Conclusions: Health systems are increasingly dedicating efforts to transitional care improvement programs. This feasibility trial will confirm whether patients and their caregivers can learn to use a postdischarge wound monitoring smartphone app and will assess patient and provider satisfaction. This protocol will provide preliminary evidence for a shift in the delivery of postdischarge care in a patient-centered and cost-effective manner. Trial Registration: NCT02735525; (Archived by WebCite at

  • Fundus photo showing scatter laser surgery for diabetic retinopathy. Image credit: National Eye Institute (NEI)/National Institutes of Health (NIH), from, licensed under cc-by-4.0. Original image in jpg format.

    Statins and Fibrates for Diabetic Retinopathy: Protocol for a Systematic Review


    Background: Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus, and more than 75% of patients who have had diabetes for more than 20 years will have some degree of DR. This disease is highly destructive to self-esteem and puts a high burden on public health and pension systems due to the effects that it has on people of working age. The current mainstay of treatment is laser photocoagulation, which causes impairment of vision and discomfort to patients. Thus, finding a systemic drug that could act on all microcirculation and prevent direct manipulation of the eyes would be highly desirable. Objective: To assess the efficacy and safety of the drugs in the statin and/or fibrate groups for the prevention and treatment of DR. Methods: In this systematic review, we will select randomized controlled trials of fibrates or statins used for the treatment or prevention of DR. Our search strategy will include free text terms and controlled vocabulary (eg, MeSH, Emtree) for, “diabetic retinopathy”, “statins”, “fibrates”, “hypolipidemic agents”, and for drugs from both groups. Databases that will be used include Medical Literature Analysis and Retrieval System/PubMed, Embase, Cochrane Central Register of Controlled Trials, Latin American and Caribbean Center on Health Sciences Information,, World Health Organization International Clinical Trials Registry Platform, and OpenGrey, and we will not have language or date limits. Two review authors will independently select eligible studies and assess the risk of bias using the Cochrane Collaboration’s tool. We will report structured summaries of the included studies and, if possible, conduct meta-analyses. Results: This is a protocol for a systematic review, therefore results are not available. We registered a short version of this protocol before progressing in the review and we are currently in the process of selecting the studies for inclusion. Conclusions: Intensive glucose control and lowering blood pressure and lipids are mechanisms that protect macrocirculation in diabetic patients. Both macrovascular and microvascular events in diabetic patients appear to have a common pathway, starting with endothelial injury. Thus, prevention and treatment of microvascular events may benefit from the same interventions. In the review for which we have written this protocol, we will assess whether the use of lipid-lowering oral drugs of the statin and/or fibrate groups may prevent and/or retard progression of DR, with the added benefit of preserving visual acuity. Clinical Trial: PROSPERO CRD42016029746

  • Image Source: chany14 via FlickR/ / CC BY-ND.

    Dance for Adults With Fibromyalgia—What Do We Know About It? Protocol for a Scoping Review


    Background: Fibromyalgia is a chronic disorder characterized by widespread muscular tenderness, pain, fatigue, and cognitive difficulties. Nonpharmacological treatment options, such as physical activity, are important for people with fibromyalgia. There are strong recommendations to support engagement in physical activity for symptom management among adults with fibromyalgia. Dance is a mode of physical activity that may allow individuals with fibromyalgia to improve their physical function, health, and well-being. Dance has the potential to promote improved pain processing while simultaneously providing the health and social benefits of engaging in physical activity that contributes to symptom management. However, we are unaware of current evidence on dance as a nonpharmacological/physical activity intervention for adults with fibromyalgia. Objective: The aims of the study are to provide an overview of the extant evidence to understand how dance is used for individuals with fibromyalgia; to examine the extent, range, and nature of research activity in the area; and to determine the value of undertaking a full systematic review. Methods: Scoping reviews are useful to comprehensively and systematically map the literature and identify key evidence, or research gaps. The search strategy will involve electronic databases including Medline, Embase, Cochrane Library, PsycInfo, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Literature in the Health Sciences in Latin America and the Caribbean (LILACS), Allied and Complementary Medicine (AMED), International Bibliography of Theatre and Dance, Physiotherapy Evidence Database (PEDro), Trip, Proquest Theses/Dissertations, Web of Science, World Health Organization International Clinical Trials Registry Platform, and The study will be mapped in seven stages: (1) identifying the research questions, (2) identifying relevant studies, (3) selecting the studies, (4) charting the data, (5) collating, summarizing and reporting the results, (6) consulting, and (7) disseminating the knowledge. Results: The search, title, and abstract are now completed; full text screening was carried out and authors are awaiting interlibrary loans and translations. Data extraction will start shortly after full text ‘screening’ is completed. Completion is expected in Fall 2017. Conclusions: To our knowledge this will be the first attempt to systematically identify knowledge of dance as a potential intervention for adults with fibromyalgia. This scoping review offers a feasible means for describing the evidence specific to dance and fibromyalgia; results will provide unique insights concerning the breadth and depth of literature in the area. An analysis of this body of literature as a whole may reveal new research directions or unknown ways this intervention could strengthen current management approaches of the disease.

  • Example of description of a service displayed in the servi-Share Web-app.

    Co-creating and Evaluating a Web-app Mapping Real-World Health Care Services for Students: The servi-Share Protocol


    Background: University students aged 18-30 years are a population group reporting low access to health care services, with high rates of avoidance and delay of medical care. This group also reports not having appropriate information about available health care services. However, university students are at risk for several health problems, and regular medical consultations are recommended in this period of life. New digital devices are popular among the young, and Web-apps can be used to facilitate easy access to information regarding health care services. A small number of electronic health (eHealth) tools have been developed with the purpose of displaying real-world health care services, and little is known about how such eHealth tools can improve access to care. Objective: This paper describes the processes of co-creating and evaluating the beta version of a Web-app aimed at mapping and describing free or low-cost real-world health care services available in the Bordeaux area of France, which is specifically targeted to university students. Methods: The co-creation process involves: (1) exploring the needs of students to know and access real-world health care services; (2) identifying the real-world health care services of interest for students; and (3) deciding on a user interface, and developing the beta version of the Web-app. Finally, the evaluation process involves: (1) testing the beta version of the Web-app with the target audience (university students aged 18-30 years); (2) collecting their feedback via a satisfaction survey; and (3) planning a long-term evaluation. Results: The co-creation process of the beta version of the Web-app was completed in August 2016 and is described in this paper. The evaluation process started on September 7, 2016. The project was completed in December 2016 and implementation of the Web-app is ongoing. Conclusions: Web-apps are an innovative way to increase the health literacy of young people in terms of delivery of and access to health care. The creation of Web-apps benefits from the involvement of stakeholders (eg, students and health care providers) to correctly identify the real-world health care services to be displayed.

  • A. The NanoKnife IRE console. B. The console operates with 19G monopolar needle electrodes, which are bundled together using the external spacers.

    Irreversible Electroporation for the Ablation of Renal Cell Carcinoma: A Prospective, Human, In Vivo Study Protocol (IDEAL Phase 2b)


    Background: Irreversible electroporation (IRE) is an emerging technique delivering electrical pulses to ablate tissue, with the theoretical advantage to overcome the main shortcomings of conventional thermal ablation. Recent short-term research showed that IRE for the ablation of renal masses is a safe and feasible treatment option. In an ablate and resect design, histopathological analysis 4 weeks after radical nephrectomy demonstrated that IRE-targeted renal tumors were completely covered by ablation zone. In order to develop a validated long-term IRE follow-up study, it is essential to obtain clinical confirmation of the efficacy of this novel technology. Additionally, follow-up after IRE ablation obliges verification of a suitable imaging modality. Objective: The objectives of this study are the clinical efficacy and safety of IRE ablation of renal masses and to evaluate the use of cross-sectional imaging modalities in the follow-up after IRE in renal tumors. This study conforms to the recommendations of the IDEAL Collaboration and can be categorized as a phase 2B exploration trial. Methods: In this prospective clinical trial, IRE will be performed in 20 patients aged 18 years and older presenting with a solid enhancing small renal mass (SRM) (≤4 cm) who are candidates for ablation. Magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS) will be performed at 1 day pre-IRE, and 1 week post-IRE. Computed tomography (CT), CEUS, and MRI will be performed at 3 months, 6 months, and 12 months post-IRE. Results: Presently, recruitment of patients has started and the first inclusions are completed. Preliminary results and outcomes are expected in 2018. Conclusions: To establish the position of IRE ablation for treating renal tumors, a structured stepwise assessment in clinical practice is required. This study will offer fundamental knowledge on the clinical efficacy of IRE ablation for SRMs, potentially positioning IRE as ablative modality for renal tumors and accrediting future research with long-term follow-up. Trial Registration: registration number NCT02828709; (archived by WebCite at Dutch Central Committee on Research Involving Human Subjects NL56935.018.16

  • IPD Prospective Meta-analysis VESPRO Collaboration.

    VESPRO: An Individual Patient Data Prospective Meta-Analysis of Selective Internal Radiation Therapy Versus Sorafenib for Advanced, Locally Advanced, or...


    Background: Untreated advanced hepatocellular carcinoma (HCC) has an overall poor prognosis. Currently there are 2 ongoing prospective randomized controlled trials that are evaluating the efficacy and safety of sorafenib and selective internal radiation therapy (SIRT) with yttrium-90 resin microspheres in patients with advanced HCC. The SorAfenib versus Radioembolisation in Advanced Hepatocellular carcinoma (SARAH; 459 patients) trial is being performed in Europe and the SIRt VErsus SorafeNIB (SIRveNIB; 360 patients) trial in the Asia Pacific region. Prospectively combining the results, these trials will not only allow for increased precision to estimate efficacy (in terms of survival), but will also provide increased statistical power for subgroup analyses. Objective: To ensure the prospectivity and transparency of the meta-analysis. Methods: The sirVEnib and SARAH merge PROject (VESPRO) is an individual, patient-data prospective meta-analysis of the SIRveNIB and SARAH randomized trials. The VESPRO protocol includes prespecified hypotheses, inclusion criteria, and outcome measures. The primary outcome measure is overall survival and secondary outcomes include tumor response rate, progression-free survival, progression in the liver as first event, and disease control in the liver. Pooling of toxicity results will allow for robust safety profiles to be established for both therapies, and provides increased statistical power to investigate treatment effects in key subgroups. Analyses will be performed in the intent-to-treat population stratified by trial. Results: Both studies are expected to demonstrate a survival benefit for SIRT together with a better toxicity profile compared with sorafenib. It is also anticipated that liver progression as the first event would be longer in the intervention compared with the control. Conclusions: As the results of the 2 trials are not yet known, the methodological strength is enhanced, as biases inherent in conventional meta-analyses are avoided. This has the effect of providing this meta-analysis with the advantages of a single, large,randomized study of 819 patients. It is anticipated that the SARAH and SIRveNIB trial results will be published separately and together with the combined meta-analysis results from VESPRO. The combined dataset will allow the effect of the interventions to be explored with improved reliability/precision with respect to prespecified patient and intervention-level characteristics. Trial Registration: Australian New Zealand Trials Registry: ACTRN12617000030370.

  • Vascular View. Image sourced and copyright owned by authors.

    Self-Management Support Program for Patients With Cardiovascular Diseases: User-Centered Development of the Tailored, Web-Based Program Vascular View


    Background: In addition to medical intervention and counseling, patients with cardiovascular disease (CVD) need to manage their disease and its consequences by themselves in daily life. Objective: The aim of this paper is to describe the development of “Vascular View,” a comprehensive, multi-component, tailored, Web-based, self-management support program for patients with CVD, and how this program will be tested in an early randomized controlled trial (RCT). Methods: The Vascular View program was systematically developed in collaboration with an expert group of 6 patients, and separately with a group of 6 health professionals (medical, nursing, and allied health care professionals), according to the following steps of the intervention mapping (IM) framework: (1) conducting a needs assessment; (2) creating matrices of change objectives; (3) selecting theory-based intervention methods and practical applications; (4) organizing methods and applications into an intervention program; (5) planning the adaption, implementation, and sustainability of the program, and (6) generating an evaluation plan. Results: The needs assessment (Step 1) identified 9 general health problems and 8 determinants (knowledge, awareness, attitude, self-efficacy, subjective norm, intention, risk perception, and habits) of self-managing CVD. By defining performance and change objectives (Step 2), 6 topics were distinguished and incorporated into the courses included in Vascular View (Steps 3 and 4): (1) Coping With CVD and its Consequences; (2) Setting Boundaries in Daily Life; (3) Lifestyle (general and tobacco and harmful alcohol use); (4) Healthy Nutrition; (5) Being Physically Active in a Healthy Way; and (6) Interaction With Health Professionals. These courses were based on behavioral change techniques (BCTs) (eg, self-monitoring of behavior, modeling, re-evaluation of outcomes), which were incorporated in the courses through general written information: quotes from and videos of patients with CVD as role models and personalized feedback, diaries, and exercises. The adoption and implementation plan (Step 5) was set up in collaboration with the members of the two expert groups and consisted of a written and digital instruction manual, a flyer, bimonthly newsletters, and reminders by email and telephone to (re-)visit the program. The potential effectiveness of Vascular View will be evaluated (Step 6) in an early RCT to gain insight into relevant outcome variables and related effect sizes, and a process evaluation to identify intervention fidelity, potential working mechanisms, user statistics, and/or satisfaction. Conclusion: A comprehensive, multi-component, tailored, Web-based, self-management support program and an early RCT were developed in order to empower patients to self-manage their CVD. Trial Registration: Nederlands Trial Register NTR5412; (Archived by WebCite at

  • Woman working in hospital. Photo credit: Stanford EdTech. Image source: Flickr licensed under Creative Commons BY-NC-ND 2.0.

    Local Anesthesia Versus Local Anesthesia and Conscious Sedation for Inguinal Hernioplasty: Protocol of a Randomized Controlled Trial


    Background: Conscious sedation is regularly used in ambulatory surgery to improve patient outcomes, in particular patient satisfaction. Reports suggest that the addition of conscious sedation to local anesthesia for inguinal hernioplasty is safe and effective in improving patient satisfaction. No previous randomized controlled trial has assessed the benefit of conscious sedation in this regard. Objective: To determine whether the addition of conscious sedation to local anesthesia improves patient satisfaction with inguinal hernioplasty. Methods: This trial is designed as a single-center, randomized, placebo-controlled, blinded trial of 148 patients. Adult patients diagnosed with a reducible, unilateral inguinal hernia eligible for hernioplasty using local anesthesia will be recruited. The intervention will be the use of intravenous midazolam for conscious sedation. Normal saline will be used as placebo in the control group. The primary outcome will be patient satisfaction, measured using the validated Iowa Satisfaction with Anesthesia Scale. Secondary outcomes will include intra- and postoperative pain, operative time, volumes of sedative agent and local anesthetic used, time to discharge, early and late complications, and postoperative functional status. Results: To date, 171 patients have been recruited. Surgery has been performed on 149 patients, meeting the sample size requirements. Follow-up assessments are still ongoing. Trial completion is expected in August 2017. Conclusions: This randomized controlled trial is the first to assess the effectiveness of conscious sedation in improving patient satisfaction with inguinal hernioplasty using local anesthesia. If the results demonstrate improved patient satisfaction with conscious sedation, this would support routine incorporation of conscious sedation in local inguinal hernioplasty and potentially influence national and international hernia surgery guidelines. Trial registration: NCT02444260; (Archived by WebCite at

  • Involving Children With Cancer in Health Promotive Research. Image Source: the authors. Image is owned by the authors.

    Involving Children With Cancer in Health Promotive Research: A Case Study Describing Why, What, and How


    Background: Participatory research approaches have been introduced to meet end-users’ needs in the development of health promotion interventions among children. However, whereas children are increasingly involved as passive informants in particular parts of research, they are rarely involved as partners, equal to adult researchers, throughout the research process. This is especially prominent in the context of child health where the child is commonly considered to be vulnerable or when the research concerns sensitive situations. In these cases, researchers and gatekeepers to children’s involvement base their resistance to active involvement of children on potential adverse effects on the accuracy or quality of the research or on ethical or moral principles that participation might harm the child. Thus most research aimed at developing health promotion interventions for children in health care is primarily based on the involvement of parents, caregivers, and other stakeholders. Objective: The objective of this paper is to discuss reasons for involving children in health promotive research and to explore models for children’s participation in research as a basis for describing how researchers can use design methodology and participatory approaches to support the participation and contribution of children in a vulnerable context. Methods: We developed and applied a model for children's participation in research to the development of a digital peer support service for children cancer survivors. This guided the selection of appropriate research and design methodologies (such as interviews, focus groups, design sessions, and usability evaluation) for involving the children cancer survivors (8-12 years) in the design of a digital peer support service. Results: We present a model for what children’s participation in research means and describe how we practically implemented this model in a research project on children with cancer. This paper can inform researchers in their planning of strategies for children’s participation and ensure future development of health promotion interventions for children is based on their perspectives. Conclusions: Challenges in reaching a suitable degree of participation during a research project involve both creating opportunities for children to have genuine influence on the research process and organizing this involvement so that they feel they understand what they are involved in and why. To achieve this, it is essential to enable children to be involved in research over time to gain confidence in the researchers and to develop children’s abilities to make decisions throughout the research processes.

  • Healthy older adult. Image source: Copyright: CC0 License.

    Protocol for a 24-Week Randomized Controlled Study of Once-Daily Oral Dose of Flax Lignan to Healthy Older Adults


    Background: Increased oxidative stress and inflammation are associated with aging, and contribute to an increased risk of chronic disease in older adults. Flaxseed lignans demonstrate antioxidant and anti-inflammatory activity, but their ability to reduce oxidative stress and inflammation markers in older adult populations has received limited investigation. Objective: This is a chronic intervention trial of community-dwelling healthy older adults to examine the effects of a flaxseed lignan (secoisolariciresinol diglucoside; SDG) enriched supplement (BeneFlax) compared to a placebo. The primary aim was to demonstrate the safety of BeneFlax and confirm its anti-inflammatory efficacy on markers of oxidative stress and inflammation, and subsequent functional outcomes, including those associated with its anti-inflammatory efficacy. A secondary aim was to determine flaxseed lignan metabolite concentrations in blood. Methods: A double-blind randomized clinical trial was conducted. Subjects were healthy community-dwelling adults aged 60-80 years. Testing was performed at baseline, 8, 16, and 24 weeks. The 24-week intervention consisted of 600 milligrams (mg) of SDG daily or an equivalent amount (volume) of placebo. All participants received 1000 international units of vitamin D to ensure adequate vitamin D status. Measurements consisted of blood pressure, hematology, and tolerability for safety assessments; blood oxidative stress and inflammatory biomarkers for efficacy; and cognition, muscle strength, and pain as functional outcomes. Secondary endpoints of plasma levels of lignan metabolites were analyzed by mass spectrometry. Other tests, such as bone turnover markers and fecal levels of flax cyclolinopeptides, will be performed at a later date. Results: Thirty-two participants were recruited (19 intervention and 13 control) and all completed the trial. Numerous Health Canada-imposed exclusion criteria limited recruitment success. Analyses are ongoing, but the baseline data available for a number of parameters indicate no differences between treatment groups. Safety measures (vital signs) did not change from baseline and were not significantly different between treatment and placebo groups at 24 weeks. Conclusions: Preliminary results indicate that no safety concerns are associated with administering 600 mg SDG for 24 weeks to adults between the ages of 60 and 80 years. Trial Registration: NCT01846117; (Archived by WebCite at

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  • HomeStyles, A Childhood Obesity Prevention Program for Families with Preschool Children: Design and Methods

    Date Submitted: Feb 21, 2017

    Open Peer Review Period: Feb 22, 2017 - Mar 8, 2017

    The home environment is where young children spend most of their time and is critically important to supporting behaviors that promote health and prevent obesity. However, the home environment and li...

    The home environment is where young children spend most of their time and is critically important to supporting behaviors that promote health and prevent obesity. However, the home environment and lifestyle patterns remain understudied and few interventions have investigated parent-led makeovers designed to create home environments that are supportive of optimal child health and healthy child weights. To our knowledge, HomeStyles is the first large-scale, rigorously controlled study to test the effectiveness of a multifactorial childhood obesity prevention program that aims to help parents of preschool children shape their home environments and lifestyle practices using quick, easy, low- or no-cost strategies. The thoughtfully developed, evidence-based, behaviorally focused, theory-driven content of the intervention materials is expected to enable and motivate parents to promote optimal home environments, lifestyle practices, and child growth, health, and body weights. A rigorous randomized controlled trial utilizing an experimental group and attention control group receiving a bona fide, contemporaneous treatment equal in non-specific treatment effects and differing only in subject matter content will test the effect of HomeStyles on a diverse sample of families with preschool children. This intervention is based on social cognitive theory and uses a social ecological framework. It will assess intrapersonal characteristics (dietary intake, physical activity level, and sleep) of parents and children; family interpersonal or social characteristics related to diet, physical activity, media use, and parental values and self-efficacy for obesity-protective practices; and home environment food availability, physical activity space and supports in and near the home, and media availability and controls in the home. This paper describes the rationale for HomeStyles, its logic model, and study design and methods.

  • The Paget Trial: A multi-centre, observational cohort, intervention study for the clinical efficacy, safety and immunological response of topical 5% imiquimod cream for vulvar Paget’s disease

    Date Submitted: Feb 14, 2017

    Open Peer Review Period: Feb 21, 2017 - Mar 7, 2017

    Background: Vulvar Paget disease is a rare skin disorder which is most common in postmenopausal, Caucasian women. They usually present with an erythematous plaque which may show fine or typical ‘cak...

    Background: Vulvar Paget disease is a rare skin disorder which is most common in postmenopausal, Caucasian women. They usually present with an erythematous plaque which may show fine or typical ‘cake icing’ scaling or ulceration, and may cause itching, pain, irritation or a burning sensation. Although most cases are non-invasive, vulvar Paget disease may be invasive, or associated with an underlying vulvar or distant adenocarcinoma. The histological evidence of so-called ‘Paget cells’, with abundant pale cytoplasm in the epithelium confirms the diagnosis. The origin of these Paget cells is still unclear. Treatment of choice is wide local excision with negative margins. Obtaining clear surgical margins is challenging and may lead to extensive and mutilating surgery. Even then, recurrence rates are high: ranging from 15 to 70%, which emphasizes the need for new treatment options. A number of case reports, retrospective case series and one observational study have shown promising results using the topical immune response modifier imiquimod. Topical 5% imiquimod cream might be an effective and safe treatment alternative for vulvar Paget disease. This study aims to investigate the efficacy, safety and immunological response in patients with non-invasive vulvar Paget disease using a standardized treatment schedule with 5% imiquimod cream. Objective: This study aims to investigate the efficacy, safety and immunological response in patients with non-invasive vulvar Paget disease using a standardized treatment schedule with 5% imiquimod cream. Methods: The Paget Trial is a multi-centre observational cohort study including eight tertiary referral hospitals in the Netherlands. Twenty patients with (recurrent) non-invasive vulvar Paget disease will be treated with topical 5% imiquimod cream 3 times a week, for 16 weeks. The primary efficacy outcome is the reduction in lesion size at 12 weeks after end of treatment. Secondary outcomes are safety, immunological response and quality of life. Safety will be assessed by evaluation of adverse events and tolerability of treatment. To evaluate the immunological response, various immunological markers will be tested on biopsy specimens taken before, during and after treatment. Quality of life will be assessed with three questionnaires taken before, during and after treatment. This study is registered at the Central Committee on Research Involving Human Subjects (CCMO) Register NL51648.091.14, NCT02385188. Results: Patients are currently enrolling in the study. First results are expected in the Summer of 2018. Conclusions: This is the first prospective trial investigating the clinical efficacy, safety, quality of life and immunological response of topical 5% imiquimod cream for vulvar Paget disease, using a standardized treatment schedule. Clinical Trial: Central Committee on Research Involving Human Subjects (CCMO) Register NL51648.091.14, NCT02385188.

  • PAin Improvement with Novel Combination Analgesic REgimens: The PAIN-CARE Trial

    Date Submitted: Feb 10, 2017

    Open Peer Review Period: Feb 21, 2017 - Mar 7, 2017

    Background: Neuropathic pain (NP, including painful diabetic neuropathy, postherpetic neuralgia etc.), affects ~7-8% of the population and is associated with a devastating symptom burden as well as a...

    Background: Neuropathic pain (NP, including painful diabetic neuropathy, postherpetic neuralgia etc.), affects ~7-8% of the population and is associated with a devastating symptom burden as well as a profound economic impact for patients, their families and the healthcare system. Current therapies have limited efficacy and dose-limiting adverse effects (AEs). Rational combination therapy with carefully selected NP drugs has shown potential for measurable improvements in pain relief, quality of life and healthcare utilization. Today, over half of NP patients concurrently receive 2 or more analgesics but combination use is based on little evidence. Research is urgently needed to identify safer, more effective, combinations. Objective: We hypothesize that analgesic combinations containing at least one non-sedating agent would be as safe but more effective than either monotherapy because of additive pain relief without increasing overall AEs. Pregabalin (PGB), a sedating anticonvulsant, is proven effective for NP and the antioxidant, alpha-lipoic acid (ALA), is one of the only non-sedating systemic agents proven effective for NP. Thus, we will conduct a clinical trial to compare a PGB-ALA combination to each monotherapy for NP. Methods: Using a double-blind, double-dummy, crossover design, 54 adults with NP will be randomly allocated to one of six sequences of treatment with PGB, ALA and PGB-ALA combination. During each of three different treatment periods, participants will take two sets of capsules containing 1) ALA (or placebo) and 2) PGB (or placebo) for 31 days, followed by an 11-day taper/washout period. The primary outcome will be mean daily pain intensity (0-10) at maximally tolerated doses (MTD) during each period. Secondary outcomes, assessed at MTD, will include global improvement, adverse events, mood, and quality of life. Results: This trial was registered in the International Standard Randomised Controlled Trial registry January 6, 2017 (ISRCTN #14577546), attained ethics approval December 15, 2016 (Queen’s University Health Sciences Sciences & Affiliated Teaching Hospitals Research Ethics Board protocol number ANAE-305-16), and recruitment is set to start March 2017. Conclusions: This trial will provide rigorous evidence comparing the efficacy of a PGB-ALA combination to PGB alone and ALA alone in the treatment of NP. Clinical Trial: International Standard Randomised Controlled Trial Number ISRCTN14577546, registered January 6, 2017.

  • Stroke Avoidance for Children in REpública Dominicana (SACRED): A Prospective Study of Stroke Risk and Hydroxyurea Treatment in Sickle Cell Anemia

    Date Submitted: Feb 10, 2017

    Open Peer Review Period: Feb 21, 2017 - Mar 7, 2017

    Background: In the Dominican Republic, where the sickle cell burden is high, many children lack access to routine screening and preventative care. Children with sickle cell anemia (SCA) are at risk fo...

    Background: In the Dominican Republic, where the sickle cell burden is high, many children lack access to routine screening and preventative care. Children with sickle cell anemia (SCA) are at risk for stroke, an event that leads to significant morbidity and mortality. In the United States, screening via Transcranial Doppler (TCD) identifies children with SCA at highest stroke risk, allowing early intervention with blood transfusions. The need for indefinite transfusions for primary stroke prevention limits their practicality in limited-resource countries. Hydroxyurea has been shown to lower TCD velocities and to prevent conversion from conditional (170-199 cm/sec) to abnormal (≥200 cm/sec) velocities. In resource-limited settings, implementation of a TCD screening program, coupled with hydroxyurea therapy, could reduce the burden of SCA and stroke. Objective: SACRED aims to screen children with SCA for stroke risk using TCD, to determine the prevalence of elevated velocities in a cross-sectional sample, to identify clinical and laboratory correlates of elevated velocities, to obtain longitudinal data on the natural history of TCD velocities, and to measure effects of hydroxyurea. Methods: This prospective trial designed and conducted by Cincinnati Children’s Hospital Medical Center (CCHMC) and Hospital Infantil Robert Reid Cabral (HIRRC) with Centro de Obstetricia y Ginecología includes a baseline cross-sectional epidemiological survey of the distribution of TCD velocities across a large cohort of children with SCA in the Dominican Republic. Children with conditional velocities are eligible to begin protocol-directed hydroxyurea if laboratory criteria are met. The treatment schedule begins with a fixed-dose of approximately 20 mg/kg/day for six months, after which it escalates to maximum tolerated dose (MTD). All participants will undergo longitudinal TCD evaluation, for a total of at least three exams per participant over a three-year study period. Data are collected using an internet-based REDCap® system with forms translated into Spanish, and both remote and on-site monitoring is used. Results: To date, 122 children with SCA have enrolled in SACRED including 85 (69.7%) with normal, 29 (23.8%) with conditional, 5 (4.1%) with abnormal, and 3 (2.5%) with inadequate TCD velocities. Seventeen children with conditional TCD velocities have initiated hydroxyurea per protocol, with plans for escalation to MTD. Conclusions: The SACRED trial will provide novel epidemiologic data about the prevalence of children with SCA and increased stroke risk in the Dominican Republic. The study also includes investigation of impact of hydroxyurea at MTD on elevated TCD velocities, as well as clinical and laboratory parameters. The design and implementation of SACRED reflect a successful international institutional partnership, one that features local capacity building and training in research methods and clinical care. The trial’s results have important implications for screening and prevention of primary stroke in children with SCA living in resource-limited settings. Clinical Trial: NCT02769845

  • Does a novel wearable device improve health related quality of life of patients with an ostomy? A prospective, observational, crossover study protocol.

    Date Submitted: Feb 12, 2017

    Open Peer Review Period: Feb 20, 2017 - Mar 6, 2017

    Background: Ostomy surgeries involving the placement of an ostomy bag (colostomy, ileostomy, urostomy, etc.) have been shown to have a negative impact on health-related quality of life. To date, no s...

    Background: Ostomy surgeries involving the placement of an ostomy bag (colostomy, ileostomy, urostomy, etc.) have been shown to have a negative impact on health-related quality of life. To date, no studies have been conducted examining what impact, if any, wearable biosensors have on health-related quality of life of ostomy patients. Objective: In the present study, we plan to assess quality of life of ostomy patients using the Ostom-i alert sensor, a portable, wearable, Bluetooth linked biosensor that facilitates easier ostomy bag output measurements. We hypothesize that using the Ostom-i alert sensor will result in an improved, ostomy specific health related quality of life as compared to baseline measurement before the use of the sensor. Methods: A total of 20 ostomy patients will be screened and recruited to participate in this prospective, observational, crossover trial using Ostom-i alert sensor for one month. The primary outcome of this study will compare ostomy specific health related quality of life at baseline (prior to Ostom-i alert sensor use) to ostomy specific health-related quality of life after 2 and 4 weeks of Ostom-i use by utilizing the City of Hope Quality of Life Questionnaire for patients with an Ostomy (CoH-QOL-Ostomy). Secondary outcomes of general health related quality of life and adjustment to ostomy will be evaluated using the Medical Outcomes Study 36-item short form health survey (SF-36) and the Olbrisch Ostomy Adjustment Scale Short Form 2 (OAS-SF2). Results: Proposed benefits of mobile, internet linked personal health monitors such as the Ostom-i include a reduction in the cost of care by reducing resource utilization and infection rates, improving patient-provider communication, reducing time spent as an in-patient as well as improved quality of life. Prior studies have demonstrated decreased health related quality of life in patients with an ostomy bag. We aim to examine the extent to which the Ostom-i™ alert sensor affects health related quality of life of its users. Conclusions: The Ostom-i alert sensor has the potential to improve quality of life of users by giving them freedom and confidence to partake in daily activities with the knowledge that they can check how full their ostomy bag is in a private, discrete manner. Clinical Trial: NCT02319434, first registered 15 December 2014.

  • Impact of a pharmaceutical intervention to improve adherence of inhaled medication in asthma and COPD patients

    Date Submitted: Feb 17, 2017

    Open Peer Review Period: Feb 20, 2017 - Mar 6, 2017

    Background: Despite progress in pharmacological and non-pharmacological treatment in recent years, the burden of disease among asthma and COPD patients is high and patients may be frequently hospitali...

    Background: Despite progress in pharmacological and non-pharmacological treatment in recent years, the burden of disease among asthma and COPD patients is high and patients may be frequently hospitalized due to exacerbations. Reasons for uncontrolled disease are manifold, but are frequently associated with poor inhalation technique and non-adherence to the prescribed treatment plan which may cause substantial mortality, morbidity, and cost to the healthcare system. In this respect, the study of causes for non-adherence and the development of measures to increase respectively maintain treatment adherence, particularly in chronic diseases, is of major clinical importance. Objective: The primary objective of this study is to measure medication adherence in patients with chronic obstructive lung diseases such as asthma and COPD, and to investigate the impact of a reminder on disease outcomes and quality of life. Methods: In this ongoing prospective single-blind randomized controlled study, the adherence to inhaled medication is analyzed over a six-months period in at least 154 in- and outpatients with asthma or COPD, who have experienced at least one exacerbation during the last year. Adherence is measured using electronic data capture devices which save date and time of each inhalative device actuation and transfer these data daily via wireless-connection to a web-based database. Patients are randomly assigned to an intervention, respectively control group. Patients assigned to the intervention group will receive audio reminder and support calls in case medication is not been taken as prescribed or if rescue medication is used more frequently than prespecified in the study protocol. During the study, participants are assessed every two months. Results: Recruitment started in January 2014 and to date, a total of 169 patients have been recruited. Follow-up assessments are still ongoing. The study will be concluded in the first quarter of 2017. Data analysis will take place during 2017. Conclusions: To date, only few studies have investigated medication adherence in patients with chronic obstructive lung diseases. With the prospective study design and the use of state-of-the-art devices for measuring adherence, we expect scientifically relevant and clinically meaningful results that will have a substantial and positive impact on the provision of health care in chronically ill patients with asthma or COPD. Clinical Trial: NCT02386722; (archives by WebCite at