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Smoking cessation treatment programs have been widely available for patients with nicotine dependence. Despite intensive programs, the continuous abstinence rate (CAR) from weeks 9-12 is still about 50%. Recently, a smartphone app emerged as a novel tool for therapeutic interventions, including nicotine dependence. In this study, we developed “CureApp Smoking Cessation” (CASC), which consists of a smartphone app for patients and a Web-based patient management software for doctors with a mobile carbon monoxide (CO) checking device to improve the efficacy of the smoking cessation treatment.
This study aims to evaluate whether the CASC app is effective for individuals with nicotine dependence in addition to standard smoking cessation programs.
This will be a randomized, sham-controlled, open-label, multicenter trial. We will recruit participants with nicotine dependence, but are otherwise healthy adults. We will randomize and allocate participants 1:1 to the CASC treatment group or a control app group. Both groups will receive a 12-week standard smoking cessation program with pharmacotherapy and counseling. In addition, participants in the treatment group will have the CASC app installed on their smartphone, which will provide video tutorials, advice from an artificial intelligence nurse, a digital diary, and measure daily exhaled CO concentration. In contrast, the control group will have the control app installed on their smartphone, where all the functions that can potentially effect smoking cessation are removed. The primary outcome will be the biochemically validated CAR from weeks 9-24. The success of smoking cessation will be defined as self-reported continuous abstinence from weeks 9-24 and exhaled CO concentration ≤10 ppm both at weeks 12 and 24. The main secondary outcomes will be the CAR from weeks 9-12, weeks 9-52, and 7-day point prevalence abstinence at weeks 4, 8, 12, 24, and 52.
We will recruit 580 participants with nicotine dependence from October 2017 to September 2018 or until the recruitment process is complete. The final 52-week follow-up will be completed in October 2019. We expect all trial results to be available by the end of 2019. The trial is funded by CureApp, Inc.
This is the first randomized controlled trial to evaluate the efficacy of CASC. We expect that CASC, in addition to standard smoking cessation programs, has a significantly higher CAR during weeks 9-24 than the control app.
University Hospital Medical Information Network Clinical Trials Registry UMIN000031589; https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000033555
DERR1-10.2196/12252
Smoking is a risk factor that causes various diseases such as malignant tumors, heart disease, cerebrovascular disease, and chronic obstructive pulmonary disease [
Smoking cessation treatment programs have been widely available for patients with nicotine dependence supported by the Japanese national insurance system [
Medical apps for smartphones are emerging as “therapeutic” intervention tools to ameliorate diabetes mellitus [
Recently, we developed “CureApp Smoking Cessation” (CASC), which consists of the latest version of CureApp Smoking Cessation smartphone app for patients and a Web-based patient management software for primary physicians with a mobile CO checking device to improve the success of the smoking cessation treatment. The CASC provides users with accurate knowledge of nicotine dependence, clues to change their behaviors, and measurements of their own exhaled CO concentration levels at home. In addition, patients can share these data remotely with their primary physicians. Masaki et al reported that, in the previous prospective studies with participants using prototypes of CASC smartphone app without a mobile CO checker, the results showed the feasibility and usability in the phase I study [
Therefore, this study aims to evaluate whether the latest version of CASC in addition to a standard smoking cessation program is effective in treating individuals with nicotine dependence.
Flowchart of the trial protocol. CASC: CureApp Smoking Cessation.
We will recruit nicotine-dependent adult participants from October 2017 to September 2018 or until the recruitment process completes; we plan to follow them until October 2019. Participants who meet all inclusion criteria will be included in the trial and those fulfilling the exclusion criteria will be removed from this trial (
Randomization will be performed for eligible participants. They will be allocated 1:1 to both arms—the CASC treatment group and the control app group. Randomization will be performed by a computer-generated random sequence with stratification for smoking cessation medications.
The list of trial centers.
Number | Institution | Prefecture |
1 | Ankou Medical Clinic | Tokyo |
2 | Ayano Clinic | Saitama |
3 | BOOCS Clinic Fukuoka | Fukuoka |
4 | Chuo Naika Clinic | Tokyo |
5 | Ebisu Garden Place Clinic | Tokyo |
6 | Higashi-hie Naika | Fukuoka |
7 | Hosoda Shinryojo (clinic) | Tokyo |
8 | Inoue Naika Clinic | Ibaraki |
9 | Kanda Clinic | Tokyo |
10 | Keio University Hospital | Tokyo |
11 | Kimura-Shiro Clinic | Fukuoka |
12 | Kita Shin-Yokohama Naika Clinic | Kanagawa |
13 | Mashiba Iin (clinic) | Saitama |
14 | Maekawa Medical Clinic | Kanagawa |
15 | Miyazaki RC Clinic | Tokyo |
16 | Motosumiyoshi Kokoromi Clinic | Kanagawa |
17 | Nakameguro Atlas Clinic | Tokyo |
18 | National Center for Global Health and Medicine | Tokyo |
19 | Nemoto Geka-Seikeigeka (clinic) | Saitama |
20 | Nihonbashi Naika-Allegy Clinic | Tokyo |
21 | Nomura Iin (clinic) | Tokyo |
22 | Odayaka Life Naika Clinic | Saitama |
23 | Saitama City Hospital | Saitama |
24 | Sawayama Naika-Sougoushinryou Clinic | Fukuoka |
25 | Segawa Hospital | Saitama |
26 | Shimizu Clinic Fusa | Saitama |
27 | Shinjuku Research Park Clinic | Tokyo |
28 | Sone Clinic Shinjuku | Tokyo |
29 | Tajima Clinic | Tokyo |
30 | Tenjin Sogo Clinic | Fukuoka |
31 | Ueda Naika Clinic | Fukuoka |
In addition to the 12-week standard treatment procedure for smoking cessation [
CASC consists of a CureApp Smoking Cessation smartphone app based on a cloud system paired with a mobile CO checker for participants and a Web-based patient management software for primary care physicians. Participants in the treatment group will install the app in their smartphones and then begin taking a few minutes every day for watching a video tutorial regarding smoking cessation; in addition, participants from the treatment group will keep a digital diary of quitting smoking, chat with artificial intelligence (AI) nurse, and check their exhaled CO concentration by the mobile CO checker at least once a day. Physicians will be able to follow participants’ exhaled CO concentration data and physical conditions through a secure cloud system and review them during the clinic visits (
The trail assessment and evaluation schedule.
Assessments | Observational period | At withdrawal | ||||||
Day of registration (Day 1) | 2 weeks (Day 15) | 4 weeks (Day 29) | 8 weeks (Day 57) | 12 weeks (Day 85) | 24 weeks (Day 169) | 52 weeks (Day 366) | ||
Patients’ background | ✓ | |||||||
Tobacco Dependence Screener | ✓ | |||||||
Brinkman Indexa | ✓ | |||||||
Fagaström Test for Nicotine Dependence | ✓ | |||||||
12-item French version of the Tobacco Craving Questionnaire | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |
Kano Test for Social Nicotine Dependence | ✓ | ✓ | ✓ | ✓ | ✓ | |||
Mood and Physical Symptoms Scale | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | |
Exhaled carbon monoxide concentration | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ |
Status of nonsmoking | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ |
Status of device use | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ||
Adverse events | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ |
aBrinkman index=(number of cigarettes per day)×(number of smoking years).
Inclusion:
Participants diagnosed with nicotine dependence (Tobacco Dependence Screener≥5 points)
Participants with Brinkman index≥200
Participants who wish to quit smoking immediately
Participants who agree to receive the smoking cessation treatment program and sign the written consent form
Participants who can use a smartphone (operating system: Android 5.0 and above or iPhone 8.0 and above)
Exclusion:
Participants with severe mental illness
Participants who cannot come to their follow-up clinic visits during the 1 year
Participants who have started taking a smoking cessation medication within 1 year before the registration
Participants who plan to use any smoking cessation aids and participate in any kind of smoking cessation activities (not limited to smoking cessation therapy) outside the trial
Participants whose investigator or clinical trial doctor judged them to be unsuitable for participation in this trial owing to other reasons
On the other hand, participants from the control app group will be able to perform only 6 basic functions in their app as follows: (1) show the user guide (how to use the app); (2) enter their profile and set the start date of smoking cessation; (3) display the course of 5 visits during the 12-week treatment with a summary of objectives of each visit; (4) show the date of next appointment; (5) get the contact form for technical support; and (6) display an app version, privacy policy, and other administrative information. The other functions of the CASC app will not be incorporated in the control app. The control app will not include the mobile CO checker either. Note that exhaled CO concentrations will be measured by the medical staff at each clinic visit regardless of the study groups, and these CO data at the clinic will be used in the analysis of study outcomes.
Overview of the "CureApp Smoking Cessation". CO: carbon monoxide; IoT: Internet of Things.
The CASC, control app, and mobile CO checker delivered by CureApp Inc. (Tokyo, Japan) should be carefully managed to ensure they are not used outside the clinical trial at each medical institution. A prescription code will be required to activate the investigational device, and the control group app will be issued by sponsors specific to each practicing medical institution; these sponsors regularly (at least once a year) perform inventory confirming there will be no usage of the app outside the trial.
The CASC smartphone app was developed at CureApp Inc. supervised by the Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine. The app runs on both iOS and Android smartphones. Primary physicians will provide the app prescription code to participants at their outpatient clinics. Participants will download the app through their smartphones, activate the app entering the code, and enter their baseline data including age, sex, years of smoking, number of cigarettes per day, prescribed medications (nicotine patch or varenicline), and motivation and self-confidence regarding smoking cessation. These data will be securely sent to the cloud storage, and the AI of our system will assemble tailor-made smoking cessation programs suitable to each participant based on their personal information. Personal data stored on the cloud can be reviewed by primary physicians. The CASC app has the following 4 main components to maximize the therapeutic effects of pharmacological therapy and counseling provided by health care professionals: (1) keeping a smoking cessation diary (once a day); (2) lectures and educational videos helping its users quit smoking; (3) interactive counseling by chat-bot (AI nurse); and (4) daily measurement and recording of exhaled CO concentration levels at home through a mobile CO checker.
Regarding a Web-based personal computer software for primary doctors, it provides a data management app from patients’ CASC mobile apps and advice for physicians to follow the national clinical guidelines appropriately.
The primary outcome of this study will be the biochemically validated CAR from weeks 9-24. The success of smoking cessation has been defined as (1) self-reported continuous abstinence from weeks 9-24 and (2) exhaled CO concentration no more than 10 ppm at both weeks 12 and 24. In current smoking cessation programs, the CAR from weeks 13-24 drastically decreases, whereas our investigational device is expected to prevent this reduction by covering “treatment gaps” to promote the retention of appropriate recognition and behavioral changes. A single-arm prospective pilot study showed that a CASC app, even without a mobile CO checker, had a significantly higher CAR from weeks 9-24 than the historical cohort that had received standard smoking cessation program [
In addition, we will evaluate the following secondary outcomes: (1) 7-day point prevalence abstinence at weeks 4, 8, 12, 24, and 52; (2) the CAR from weeks 9-12 and from weeks 9-52; (3) changes in several scores related to smoking cessation, including the Mood and Physical Symptoms Scale (MPSS) [
An independent monitoring staff will conduct on-site data monitoring. In addition, the staff will review trial database to confirm whether principal and subinvestigators at each clinic perform the clinical trial according to the research proposal and standard operation procedures, and data queries will be asked if necessary.
Participants will be discontinued from follow-up visits for this trial when they meet either of the following criteria: (1) participants request discontinuation; (2) researchers consider discontinuation is necessary owing to severe adverse effects, for example; (3) the eligibility criteria was violated; (4) significant deviation from the protocol occurred; (5) study institution terminated trial participation because of good clinical practice violation, for example; (6) participants’ further follow-up visits are considered very difficult to accomplish; (7) continuing smoking even at the 9th week or participant no longer intends to continue the smoking cessation program; (8) sponsor cannot continue the trial; and (9) any other cause in which researchers decide discontinuation is appropriate.
The primary endpoint will be the CAR from weeks 9-24. We estimated conservatively 52.8% in the CASC treatment group and 40.8% in the control group as the primary endpoint (CARs from weeks 9-24) based on the survey of smoking cessation [
All statistical analyses will be performed according to the intention-to-treat principle and using 2-sided at a .05 significance level. The baseline characteristics will be described by the mean and SD, median and quantiles (continuous variables), or proportion (categorical variables). We will examine the outcomes using the full analysis set. For the primary outcome, we will compare CARs from weeks 9-24 comparing the CASC treatment group and the control group using a logistic regression model adjusted for prescribed smoking cessation medications. In addition, secondary outcomes at each defined period will be evaluated with logistic regression analysis adjusted for appropriate covariates between the groups. We will provide descriptive statistics, odds ratios, 95% CIs, and
A total of 580 participants with nicotine dependence will be recruited from October 2017 to September 2018 or until recruitment is complete. The final 52-week follow-up will be completed in October 2019. We expect that all trial results will be available by the end of 2019.
This is the first randomized controlled trial to evaluate the long-term efficacy of CASC, a smoking cessation support app for participants, which also includes a Web-based software for doctors and a mobile CO checker. We expect that participants in the CASC treatment group, in addition to a 12-week standard smoking cessation program, will exhibit a significantly higher CAR from weeks 9-24 than participants in the control app group.
In recent years, several medical apps for smartphones have shown better clinical outcomes compared with conventional treatment [
We developed and used a mobile Internet of Things (IoT) device to measure an exhaled CO concentration level in this trial. A level of exhaled CO concentration is a useful biomarker for patients with nicotine dependence [
There are several benefits to including smartphone apps with an IoT device to clinical settings. First, a mobile app covers treatment gaps between the outpatient clinic visits. It is beneficial to continuously contact participants and keep providing effective treatment programs, which could be one of the most important points for the program success [
Improving nicotine dependence treatment programs with therapeutic smartphone apps and IoT devices is important in terms of preventing chronic obstructive pulmonary disease, cardio- and cerebrovascular diseases, and malignant tumors. In addition, these mobile apps and devices can contribute to preventing secondhand smoke, which kills approximately 15,000 people every year in Japan [
artificial intelligence
continuous abstinence rate
CureApp Smoking Cessation
carbon monoxide
12-item French version of the Tobacco Craving Questionnaire
Internet of Things
Kano Test for Social Nicotine Dependence
Mood and Physical Symptoms Scale
The authors thank all participants and staff involved in this trial. They also thank Dr Tomoko Betsuyaku for her outstanding support of us and this trial. Furthermore, the authors thank Editage (Tokyo, Japan) for English language editing.
This trial is supported by CureApp, Inc. AN has received consulting fees from CureApp, Inc. HT and KF have received honoraria from CureApp, Inc. TM is an employee of CureApp, Inc. KS and SS are the founders and shareholders of CureApp, Inc. and patent holders of the CASC. EH has a consultation contract as a biostatistician with CureApp, Inc. KM has nothing to disclose.