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Insomnia symptoms are a common form of sleep difficulty among people with type 2 diabetes (T2D) affecting sleep quality and health outcomes. Several interventional approaches have been used to improve sleep outcomes in people with T2D. Nonpharmacological approaches, such as cognitive behavioral therapy for insomnia (CBT-I), show promising results regarding safety and sustainability of improvements, although CBT-I has not been examined in people with T2D. Promoting sleep for people with insomnia and T2D could improve insomnia severity and diabetes outcomes.
The objective of this study is to establish a protocol for a pilot randomized controlled trial (RCT) to examine the effect of 6 sessions of CBT-I on insomnia severity (primary outcome), sleep variability, and other health-related outcomes in individuals with T2D and insomnia symptoms.
This RCT will use random mixed block size randomization with stratification to assign 28 participants with T2D and insomnia symptoms to either a CBT-I group or a health education group. Outcomes including insomnia severity; sleep variability; diabetes self-care behavior (DSCB); glycemic control (A1c); glucose level; sleep quality; daytime sleepiness; and symptoms of depression, anxiety, and pain will be gathered before and after the 6-week intervention. Chi-square and independent
This study recruitment began in February 2019 and was completed in September 2019.
The intervention, including 6 sessions of CBT-I, will provide insight about its effect in improving insomnia symptoms, sleep variability, fatigue, and diabetes-related health outcomes in people with T2D and those with insomnia symptoms when compared with control.
ClinicalTrials.gov NCT03713996; https://clinicaltrials.gov/ct2/show/NCT03713996
DERR1-10.2196/14647
Type 2 diabetes (T2D) is the predominant form of diabetes mellitus that results in multiple complications, including sleep difficulties [
Sleep disturbances have been shown to increase activation of the hypothalamic-pituitary-adrenal (HPA) axis [
Insomnia is one of the most common sleep disorders in people with T2D, as more than half of their population report insomnia symptoms [
For adults and older adults diagnosed with clinical insomnia, there are several negative effects of insomnia that are harmful to long term health, such as increases in daytime sleepiness, fall risk, fatigue, and a decline in the quality of life [
Although individuals with T2D or insomnia are at increased risk of negative health outcomes, there are also unique risks to those who have both T2D and insomnia. People with T2D who experience poor sleep quality or excessive daytime sleepiness show decreased adherence to diabetes self-care behavior (DSCB) [
T2D and insomnia have a bidirectional relationship, which might be because of shared risk factors [
Pharmacological approaches for treating insomnia have potentially serious side effects on health. Several studies have shown an association between sleeping pill prescriptions and mortality in different populations [
The American Academy of Sleep Medicine recommends cognitive behavioral therapy for insomnia (CBT-I) as the first line of treatment for people with insomnia [
The primary objective of this study is to establish a protocol for a pilot study to (1) investigate the effect of 6 sessions of CBT-I on insomnia severity in people with T2D and insomnia symptoms and (2) explore the effect of 6 sessions of CBT-I on sleep variability; fatigue; A1c; DSCB; sleep quality; daytime sleepiness; and the severity of depression, anxiety, and pain in people with T2D and insomnia symptoms. We hypothesized that people in the CBT-I group will have greater improvement in insomnia severity, sleep variability, fatigue, A1c, DSCB, sleep quality, daytime sleepiness, and severity of depression, anxiety, and pain compared with people receiving only health education (HE). We anticipate the improvement in insomnia severity will positively impact people with T2D and health outcomes because of the relationship between insomnia symptoms and diabetes-related health outcomes.
The study design will be a pilot randomized controlled trial (RCT). This study will have an allocation ratio of 1:1, and this pilot RCT will be using a superiority framework to test the effectiveness of the experimental CBT-I intervention. This protocol is in accord with the Standard Protocol Items: Recommendations for Interventional Trials 2013 statement [
This study will be conducted at the University of Kansas Medical Center (KUMC) in the United States. The study sites are also listed on ClinicalTrials.gov [
The inclusion and exclusion criteria are shown in
Aged between 40 and 75 years.
Have a type 2 diabetes diagnosis.
Have a score of >10 on Insomnia Severity Index that indicates clinical insomnia—in addition, we will ask for reported symptoms of difficulty falling asleep, maintaining sleep, or waking up too early at least three nights/week for the past 3 months.
Are able to understand and follow verbal commands in English—the intervention and questionnaires are available in English only; therefore, the participants must understand English language.
Are able to travel to the University of Kansas Medical Center to attend all assessment and intervention visits at the Health Exercise and Aging Lab.
Self-reported neurological diseases (eg, Alzheimer disease, Parkinson disease, traumatic brain injury, stroke, and multiple sclerosis)
A score >4 on Stop-Bang questionnaire
Failure to pass Restless Leg Syndrome Diagnostic Index
Brief Pain Inventory score ≥7
Beck Depression Scale score ≥21
Generalized Anxiety Disorder–7 score ≥15
Pregnant women
Self-reported the following medical issues: chronic fatigue syndrome, fibromyalgia, bipolar, seizure disorders, and rheumatic diseases
Speech deficits or significant auditory impairment
Current night shift work
Heavy alcohol drinker (≥15 drinks per week for men and ≥8 for women)
Dialysis, blindness, or transfemoral amputation
In addition, during the phone screening, we will exclude the following people: 1) Those with scores >4 on Stop Bang items including snoring, tiredness, observed apnea, blood pressure, body mass index, age, neck circumference, and gender. People with sleep apnea symptoms commonly report poor sleep quality and insomnia [
During active screening session, the following interested participants will be excluded
In addition, during the active screening session, we will confirm the ages between 40 and 75 years by obtaining the date of birth. People with diabetes aged between 40 and 75 years usually present with chronic insomnia [
All intervention sessions will be delivered by a trained CBT-I provider. The CBT-I provider is a physical therapist who completed coursework and a Mini-Fellowship in Behavioral Sleep Medicine through the University of Pennsylvania. Ongoing mentorship will be provided by an experienced CBT-I provider. All participants will receive 6 sessions over the course of 6 weeks of either CBT-I or HE (ie, 1 session per week for 6 weeks). Sessions will last for 1 hour for both groups to mitigate the impact of social interaction. We chose HE sessions as usual care for people with T2D.
Sleep restriction therapy
Time in bed will be limited to the total sleep time by identifying the wake time and total sleep time to increase the sleep efficiency. We will not prescribe the total time in bed to be less than 6 hours.
Stimulus control therapy
This component strengthens the association between the bedtime and sleep only. We will ask participants to use the bed for only sleep and sexual activity to help train the brain. Participants will be asked to leave the bedroom if unable to fall asleep within 20 min and return when sleepy.
Sleep hygiene
This component will minimize the influence of negative behaviors on sleep quality and quantity. The principles and the effects of diet, exercise, caffeine, alcohol, and environment on sleep behavior will be provided.
Relaxation techniques
Diaphragmatic breathing technique promotes relaxation by using the diaphragm correctly while breathing.
Mindfulness reduces cognitive and somatic arousal. The principles of mindfulness (nonjudging, patience, trust, acceptance, and letting go) will be discussed.
Progressive muscle relaxation positively influences physiologically measured muscle tension.
Cognitive therapy changes detrimental beliefs and attitudes about sleep. We will work on reducing sleep effort, catastrophic predictions, worry about sleep, and fearing of insomnia relapse.
Insomnia relapse
This component facilitates the understanding of the risk factors of reoccurrence. We will discuss the approaches to maintain clinical gains.
Brief sleep hygiene
We will discuss 8 items of sleep hygiene including exercise, comfortable bedroom, temperature of bedroom, food, liquids, caffeine, alcohol consumption, smoking, and naps. Parts of sleep hygiene, such as consistent sleep schedule and association of bed with sleep, will not be included in this brief sleep hygiene education.
Foot care education
We will provide foot care education regarding the demographic and comorbidity, foot pathology and assessment, and preventive interventions. In addition, we will provide the American Diabetes Association recommendation regarding foot hygiene.
Causes and diagnosis of diabetes
We will provide information about diagnosis and classification of diabetes mellitus from the American Diabetes Association. The following topics will be discussed:
The definition and description of Diabetes Mellitus, classification of diabetes mellitus, and other categories of glucose regulation
Categories of increased risk for diabetes
Diagnostic criteria for diabetes mellitus
A short animation will be provided to explain how diabetes affects the body
Healthy diet education
Different dietary approaches to manage type 2 diabetes will be discussed. Articles from American Diabetes Association website will be navigated).
Physical activity education
We will use a guide for adults based on the 2008 Physical Activity Guidelines for Americans. We will discuss following points:
The timeline of the CBT-I (cognitive behavioral therapy for insomnia) intervention.
The timeline of Health Education.
Participants allocated to the CBT-I group will meet with the CBT-I provider weekly for 1 hour of CBT-I sessions. CBT-I is designed to address cognitive and behavioral factors that perpetuate insomnia [
This protocol intervention was designed based on a session-by-session guide [
Sleep restriction therapy, stimulus control therapy, and sleep hygiene will be started in this session. The sleep diary from the previous week will be reviewed to calculate the average SE from the previous 7 nights. In this session, subjects will learn the rationale and efficacy of using sleep restriction therapy and stimulus control therapy as a first line of treatment. Sleep restriction therapy is designed for individuals who are not able to initiate and/or maintain sleep [
Sleep titration, reviewing sleep hygiene, and introducing diaphragmatic breathing technique will be covered in this session. In this week, we will again review the sleep diary to confirm any necessary sleep titration (that is sleep restriction therapy adjustment). Sleep titration will be determined by measuring the individual’s SE. An SE >90% indicates positive gain that directs upward sleep opportunity. An SE between 85% and 90% score indicates marginal gain that maintains the sleep schedule. An SE <85% score indicates negative gain that directs downward sleep opportunity. If compliance issues arise during the sleep diary review, this session will focus on reinforcing the importance of sleep restriction and stimulus control therapies. Stress and anxiety symptoms are commonly reported in people with insomnia [
Similar to sessions 1 and 2, the sleep diary will be reviewed for sleep titration, and we will introduce mindfulness. Upward or downward sleep titration will be determined based on the sleep diary. Mindfulness has shown positive effects in reducing cognitive and somatic arousal when combined with CBT-I for people with insomnia [
Sleep titration and progressive muscle relaxation will be delivered in this session. Upward or downward sleep titration will be determined based on the sleep diary. Muscle relaxation therapy is a physiological intervention designed to measure and reduce muscle tension [
Sleep titration and cognitive therapy will be delivered in this session. Cognitive therapy is designed to change detrimental beliefs and attitudes about sleep. The intervention content provided in sessions 1, 2, 3, or 4 may be similar to the cognitive therapy provided in session 5, although session 5 will focus on providing the cognitive therapy intervention in its entirety. During this session, we will work on reducing sleep effort, catastrophizing, anxiety about sleep, and insomnia relapse. Also, we will work on correcting negative sleep beliefs, particularly regarding insomnia. In addition, we will work on enhancing individuals’ willingness to modify the sleep-related behaviors and engage in good strategies. Finally, we will continue working on sleep titration to optimize the SE.
Assessing global treatment gains and relapse prevention education will be the focus in this session. We will review the SE of each session to graphically demonstrate the participant’s SE over the course of this intervention. This process will help in providing information that facilitates chronic insomnia and understands the risk factors of reoccurrence. Finally, we will discuss the approaches to maintain clinical gains and fix insomnia returns, and we will schedule participants for the reassessment session.
During each session, the CBT-I provider will use 2 documentation sheets that are nonspecific to CBT-I: a checklist and tracking sheet. These sheets will help the CBT-I provider for quality assurance and standardization of treatment sessions across participants. We do not expect these sheets to contribute to the intervention or the outcomes of this study.
The participants will be called 1 day before each session to confirm their session appointment the following day and remind them to bring their completed sleep diary. In addition, a folder will be provided at the first session to keep provided materials together for review. The CBT-I sessions will be audio recorded to assess treatment integrity if the subject agrees.
CBT-I intervention fidelity will be assessed by an independent CBT-I expert who will use a scoring sheet to assess CBT-I provider’s compliance in utilizing the manual to deliver the CBT-I. The CBT-I provider will be scored on 5 scales from 0 (poor) to 6 (excellent) based on (1) how they address immediate concern, (2) how they explain the outline of the session, (3) how they discuss the sleep diary outcomes, (4) their adherence in providing the intervention, and (5) their competency in delivering each session.
Participants allocated to the HE group will meet with the CBT-I provider weekly for 1 hour of HE sessions. The HE sessions include several components including brief sleep hygiene, foot care, diabetes classifications, healthy diet, and physical activity. During all sessions, subjects will be encouraged to engage in discussion through open questions about their experience of diabetes and lifestyle as well as their comprehension of the provided materials. Similar to the CBT-I group, session tracking sheets will be used to track new difficulties or concerns and provided education.
Age, race, ethnicity, sex, marital status, education, employment, diabetes duration, medication list, and body mass index will be gathered at the first assessment session.
The Insomnia Severity Index (ISI) is a self-report measure designed to evaluate the nature, severity, and impact of insomnia [
The Actigraph device is a small, noninvasive device worn on the nondominant wrist that records limb movements using electrical impulses, and it has been validated for use in people with insomnia [
The Epworth Sleepiness Scale (ESS) uses 8 items on a 4-point Likert scale, where the subjects rate how likely they would be to fall asleep in 8 different states of daily activities. The ESS has demonstrated satisfactory psychometric properties such as test-retest reliability (r=.82) and internal consistency (alpha=.88). The cutoff point is ≥10 to distinguish between normal from pathological sleepiness [
The Pittsburgh Sleep Quality Index (PSQI) is a validated 19-item questionnaire that differentiates between poor and good sleepers. The PSQI uses 7 items on a 4-point Likert scale, and it yields a global sleep quality score that ranges from 0 to 21. Poor sleepers have scores >5, with this cutoff global PSQI score providing satisfactory sensitivity (89.6%) and specificity (86.5%). In our study, we will use a 3-factor scoring model for the PSQI (SE, perceived sleep quality, and daily disturbances), which has been tested and validated [
The diabetic care profile (DCP) uses items on 5-point Likert scales to evaluate the frequency of symptoms related to diabetes. The DCP is a validated instrument that measures self-reported diabetes control and psychological and social factors associated with the management of diabetes [
A1c will be determined using the hemoglobin A1c test by a disposable blood finger stick test using (A1cNow+ kit; TMS Company). The A1c indicates the average blood glucose level of people with diabetes over the previous 2 to 3 months and represents the current management of diabetes [
Random glucose levels will be measured using glucose meter (Contour Next EZ Blood Glucose Monitoring System, Model 7252). The results of glucose level will be presented in milligrams per deciliter to document nonfasting glucose levels [
Fatigue symptoms will be measured using the Fatigue Severity Scale (FSS), which is a 9-item questionnaire that has been validated in people with diabetes [
The BPI is a valid and reliable measure to assess painful diabetic peripheral neuropathy [
The BDI has high reliability and good validity [
The GAD-7 uses 7 items on a 3-point Likert scale. The total score of the GAD-7 ranges from 0 to 21, with higher scores indicating severe anxiety symptoms. It has been shown to be highly sensitive and specific for the detection of anxiety symptoms, and it is correlated with other anxiety scales [
All measurements will be performed at baseline and 1 week after treatment completion (
At initial contact with a potential subject, a phone screening or diabetes clinic interview will be conducted by a member of the research team to determine whether an individual qualifies to progress to an in-person screening for the study. The phone screening interview assesses participant eligibility according to age, self-report of T2D diagnosis, insomnia severity, ability to understand English, STOP-Bang score, RLS Diagnostic Index, pregnancy status, alcohol use, night-shift work, and undiagnosed neurological disorders.
Individuals passing the phone screening will be scheduled for an in-person screening session to assess eligibility according to symptoms of pain, depression, and anxiety.
Subjects will undergo the consent process in a private room at KUMC before completing any of the in-person screening assessments. Individuals passing the in-person screening will then immediately begin baseline assessment.
Consort of the project. A1c: glycemic control; BDI: Beck Depression Inventory; BPI: Brief Pain Inventory; CBT-I: cognitive behavioral therapy for insomnia; DCP: diabetic care profile DSCB: diabetes self-care behavior; ESS: Epworth Sleepiness Scale; GAD-7: Generalized Anxiety Disorder–7; ISI: Insomnia Severity Index; PSQI: Pittsburgh Sleep Quality Index; and T2D: type 2 diabetes.
To detect the effect of CBT-I on people with T2D and symptoms of insomnia, the change in pre-post ISI was used to determine sample size. Pre-post changes using the minimal clinically meaningful difference of 8 points for the ISI in a previous study [
Subjects will be recruited from diabetes and sleep clinics at KUMC, university advertisements, community centers in Kansas City, flyers, personal referrals and newsletters, and a registry of patients from KUMC who have signed up to be contacted about potential research opportunities.
We will use random mixed block size randomization [
Participant allocations will be placed in sealed envelopes. The envelopes are prepared by a research assistant, who withholds this information from the CBT-I provider. After finishing the baseline assessment, participants will be asked to open the sealed envelope to disclose their group allocation. Microsoft Excel will be used to create the randomization lists.
A computer will be used to generate the random mixed block size randomization sequences. Results of the generator will be concealed from the assessor and CBT-I provider. Participants will be asked to open the sealed enveloped after informed consent and baseline assessment are completed.
The assessor, who is blinded to group allocation, will score the Actigraph data. The assessor will have experience in scoring criteria and no involvement in providing the interventions. The CBT-I provider will not be blinded in this study.
Insomnia severity (primary outcome); sleep variability; fatigue; DSCB; A1c; daytime sleepiness; sleep quality; glucose levels; and symptoms of depression, anxiety, and pain will be measured a week before and after the intervention.
All study-related procedure will be performed at Georgia Holland laboratory in Hemenway Life Sciences Innovation Center on the KUMC campus. All obtained participant records will be kept in locked cabinet inside the Georgia Holland laboratory. Electronic study data will be saved in the KUMC Research Electronic Data Capture system. For voice records, all tapes will be saved on a secure university-supported network drive.
A chi-square test will be used to compare between-group differences in categorical variables. Independent 2-sample
For the main analysis
Owing to the complex relationship between insomnia and T2D, some factors are needed to be controlled to fully investigate the relationship. Owing to the small sample size and possible covariates that might not be included in the power calculation, these complex relationships will be investigated using exploratory analyses. Post hoc analysis using the type and number of medications will used to address the potential confounding effects on the outcomes. Univariate linear regression will be used to control for demographic and clinical variables (covariates). The decision to perform these analyses with demographic and clinical variables will be made if there are significant between-group differences at baseline in depression symptoms, anxiety symptoms, pain symptoms, gender, diabetes duration, or body mass index. Mixed models will be used to account for the correlation between times in pre- and posttest (7 nights as random factor) sleep variability (as dependent variable) and facilitate adjustment for covariates to compare the difference in sleep variability between the CBT-I and HE groups (groups as fixed factor). Covariates will be determined if there is a difference in the baseline assessment for demographic and clinical outcomes. Those participants who are treated with CPAP will be asked to report their compliance using CPAP during baseline and postintervention assessments. Subjects who are using VPAP will be given a modified sleep diary to check off nights of CPAP compliance during the assessment sessions. An exploratory subanalysis will be utilized to investigate the difference in insomnia severity between compliance and noncompliance with CPAP. Noncompliance is defined as (1) missing more than 2 nights during the 7 nights period that the participant is wearing the Actigraph or (2) using the CPAP for <4 hours per night during this study.
The primary investigator will review the dataset at least semiannually. The primary investigator’s evaluation will be focused on the quality of data collection and data management. In addition, the investigators will review data in an ongoing manner for accuracy, both at a time when these data are entered into the database and during analysis.
During the pre and postassessment sessions, testing will be stopped if the subjects show signs of low blood sugar (<70 mg/dL) or if signs of dizziness or headache are noted by the assessor or reported by the participant. During assessment sessions, participants also will be instructed to stop the test at any time for a rest break, as often as needed.
There is a risk of skin redness may be associated with wearing the Actigraph for 1 week. The risks of wearing the Actigraph are nearly the same as wearing a wrist watch. If skin redness or inflammation happened, subjects may remove the Actigraph and immediately report the symptoms to research personnel. In addition, there is a risk of minor electrical shock if the Actigraph is damaged. If damage to the Actigraph occurs, subject will be asked to return it to our lab, and they will be given a replacement.
Initially, participating in a CBT-I intervention may have an increase in sleepiness, which may impact participants’ fatigue, thinking ability, or functional abilities. It is anticipated that this increase in sleepiness will be temporary and should help participants sleep better in the long term.
During the in-person screening session, if suicidal intent is identified through either the BDI (question number 9, with a
The study will be performed in accordance with KUMC’s Institutional Review Board and Human Subjects Committee. No individuals will be excluded based on sex, race, or ethnicity. Interested participants will be administered a structured screening interview to determine their eligibility for the study. During the consent session, all interested participant will be informed about the study’s objective, risks, procedure, and potential benefits (or lack thereof).
Consent will be obtained in Georgia Holland Health Exercise and Aging Lab on the main campus of KUMC. Participants will be encouraged to ask any questions about the study as much as they need, and members of research study will answer their questions. In addition, participants will be informed if there is any change in the protocol to sign a new consent form.
All data will be deidentified and stored on the KUMC research private drive, which will be secured and backed up every night. The working dataset will be stored on a password-protected computer in the primary investigator’s laboratory, with access restricted to study researchers who are actively working with these data. All subject files and documents will be stored in a locked cabinet.
A total of 28 participants with T2D and insomnia symptoms recruited from February 2019. This study currently completed the recruitment stage. The completion date for the study was September 2019. Our results will describe the changes in insomnia severity; sleep variability; fatigue; A1c; DSCB; and severity of depression, anxiety, and pain. We will report our results in tables and figures using SPSS and GraphPad, respectively.
Our study will be the first in conducting an RCT using CBT-I for people with T2D. If this study indicates that 6 sessions of CBT-I are effective in improving sleep and diabetes outcomes in people with T2D and insomnia symptoms when compared with HE, CBT-I could be implemented as an effective and safe treatment for this population, although more research will be needed to verify the findings of this pilot RCT.
Pharmacological interventions for sleep difficulties have shown harmful effects on people with T2D. There is a need to better understand safe intervention benefits in people with T2D. This study will contribute to the management of T2D using behavioral sleep intervention as an effective and safe treatment for people with insomnia symptoms. The results will contribute to the literature by examining the effect of CBT-I on both sleep and diabetes outcomes. This will help in understanding the effectiveness of short duration intervention designed for people with insomnia symptoms.
The study strengths include utilizing important methods for people with T2D, such as objective measures, design, and safe intervention. Determining sleep variability using objective and subjective measures will accurately detect sleep improvement after an intervention. Using comparative groups to understand the effect of CBT-I on insomnia symptoms, sleep variability, fatigue, and diabetes-related health outcomes will add new information to the literature and improve the understanding of clinical conditions. Previous studies recommend optimizing the sleep quality and quantity for people with comorbidities. Understanding the effect of CBT-I in people with T2D will expand the generalizability of using this type of interventions.
Some limitations in this protocol might be important to consider in future studies. First, we will not confirm the diagnosis of T2D using the current American Diabetes Association guidelines. However, a study showed that the specificity of prevalent self-reported diabetes and incident self-reported diabetes were 84% and 97% and sensitivity of 55% and 80%, respectively, compared with fasting glucose, A1c, and/or medication use [
glycemic control
Beck Depression Inventory
Brief Pain Inventory
cognitive behavioral therapy for insomnia
Health Education
coefficient of variance
diabetic care profile
diabetes self-care behavior
Epworth Sleepiness Scale
Fatigue Severity Scale
Generalized Anxiety Disorder–7
hypothalamic-pituitary-adrenal
Insomnia Severity Index
University of Kansas Medical Center
continuous passive airway pressure
Pittsburgh Sleep Quality Index
randomized controlled trial
restless leg syndrome
sleep efficiency
sleep latency
snoring, tiredness, observed apnea, blood pressure, body mass index, age, neck circumference, and gender
type 2 diabetes
tumor necrosis factor
total sleep time
waking after sleep onset
MMA is involved in establishing the research question and protocol. AMA and SAA are involved in establishing REDcap for the data collection and data entry. JCH, JLR, CAB, JMM, PMK, and CFS are involved in establishing the protocol. MAP is involved in calculating the power. All authors approved the final version of this paper.
None declared.