Methods
Study Design
The RJ-TOMODACHI study is a single-center, 3-armed, parallel group randomized controlled trial conducted with overweight/obese adults. The trial has been designed to compare the effectiveness of 2 newly developed interventions against standard care over a period of 6 months.
Participants
Inclusion Criteria
To be eligible for enrollment in the study, patients have to fulfill the following criteria: age 25–60 years, BMI ≥27 kg/m2
and <37 kg/m2, living in Moscow or the Moscow region, Internet access (any type), and providing written informed consent.
Exclusion Criteria
Patients with cardiovascular disease (coronary artery disease, hypertension with BP >180/120 mmHg, a history of stroke, chronic heart failure [New York Heart Association Class III–IV]), diseases requiring a special diet, Type 1 or Type 2 diabetes, hyper- or hypothyroidism, cancer, dementia, a history of bariatric surgery, or those who are pregnant are excluded from the study. In addition, those taking medications that could affect BW, those who have to take frequent business trips, and shift workers are excluded from the study.
The presence exclusion criteria was determined at the time of screening.
Recruitment and Screening Procedures
Several methods were used to recruit potential participants, including regular announcements on social media and on the official website of the National Medical Research Center for Therapy and Preventive Medicine (NMRCTPM) of Russia, as well as printed advertisements near the main entrances of 2 NMRCTPM buildings.
A direct telephone line was booked for the entire recruitment period.
As part of the recruitment process, subjects were screened during physician consultations to assess their eligibility based on the inclusion and exclusion criteria.
Anthropometry Measurements
Anthropometric measurements were performed with participants wearing light clothing, without shoes or head dress, using standardized methods and equipment. Height was measured to the nearest 0.5 cm using a stadiometer. BW was measured to the nearest 0.1 kg with a calibrated scale. WC (the distance around the smallest part of the patient’s waist, just above the belly button) was measured using a measuring tape.
BP and Heart Rate Measurements
BP and pulse measurements were conducted on the right arm using an automatic digital device (INME-01; Institute of Nanotechnologies of Microelectronics [INME], Moscow, Russia). BP and pulse were measured 3 times in seated participants with their arm level with their heart. The mean of 2 measurements, excluding the first of the 3 measurements, was calculated and used in analyses.
Screening Laboratory Tests
The laboratory tests performed included clinical blood analysis (hemoglobin, erythrocyte, color index, leukocyte, erythrocyte sedimentation rate, common urine analysis [protein, glucose, ketones], lipid profile [total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, triglyceride]) and biochemical tests (fasting plasma glucose, HbA1c, creatinine, uric acid, total protein, ALT, AST, and TSH). All blood analyses were performed using the ARCHITECT analyzer (Abbott, Abbott Park, IL, USA).
After all measurements and tests, participants were invited for a consultation, at which time they were either included in the study or received recommendations based on the results of the screening.
Randomization Procedure
Randomization was computer generated in randomized blocks using software developed by Japanese researchers and Zenbe Co. (http://www.zenbe.jp/, accessed October 17, 2019). The randomization procedure was conducted at the NMRCTPM by a researcher not affiliated with the treatment, who preserved allocation anonymity, randomly separating individuals into a standard care control group, a low-intensity intervention group and a high-intensity intervention group at a ratio of 3 : 2 : 2. The researchers in charge of conducting the intervention will be informed of participants’ allocated group before the participants start their lifestyle modification.
Standard Survey at the Start of the Trial
The information and registration form contains different sections to allow for the collection of information regarding sociodemographic characteristics, history, and physical activity, an assessment of the risk factor (smoking, alcohol consumption) profile, and a food frequency questionnaire (Supplementary File 1).12–14
Interventions in the High- and Low-Intensity Intervention Groups
It is planned that participants in the high-intensity intervention group will have 6 visits during the study period (Table 1). At each visit, a nurse will measure BW, BMI, BP, hip circumference, and WC. Blood and urine samples will be obtained 3 times for testing. All participants of this group will receive self-assessment devices, as detailed below. Participants will send weekly data from their devices (Figure 1) and will keep a food diary for review at subsequent consultations.
Table 1.
Study Schedules for the High- and Low-Intensity Intervention and Standard Care Groups
| |
Visit |
| 1 |
2 |
3 |
4 |
5 |
6 |
| High-intensity intervention |
| Time relative to 1 st visit |
|
2 weeks later |
1 month later |
2 months later |
3 months later |
6 months later |
| Information registration form |
+ |
+ |
+ |
+ |
+ |
+ |
| Consultation on diet |
+ |
+ |
+ |
+ |
+ |
+ |
| Anthropometry |
+ |
+ |
+ |
+ |
+ |
+ |
| Laboratory examination |
+ |
|
|
|
+ |
+ |
| Receipt of self-monitoring devices |
+ |
|
|
|
|
|
Analysis of food diaries, check of self-
monitored data, and self-monitored data |
|
+ |
+ |
+ |
+ |
+ |
| Return of self-monitoring devices |
|
|
|
|
|
+ |
| Low-intensity intervention |
| Time relative to 1 st visit |
|
3 months later |
6 months later |
|
|
|
| Information registration form |
+ |
+ |
+ |
|
|
|
| Consultation on diet |
+ |
+ |
+ |
|
|
|
| Anthropometry |
+ |
+ |
+ |
|
|
|
| Laboratory examination |
+ |
+ |
+ |
|
|
|
| Receipt of self-monitoring devices |
+ |
|
|
|
|
|
Analysis of food diaries, check of self-
monitored data, and self-monitored data |
|
+ |
+ |
|
|
|
| Return of self-monitoring devices |
|
|
+ |
|
|
|
| Standard care group |
| Time relative to 1 st visit |
|
3 months later |
6 months later |
|
|
|
| Information registration form |
+ |
|
+ |
|
|
|
| Consultation on diet |
+ |
|
+ |
|
|
|
| Anthropometry |
+ |
+ |
+ |
|
|
|
| Laboratory examination |
+ |
|
+ |
|
|
|
It is planned that participants in the low-intensity intervention group will have 3 visits (at 3 and 6 months;
Table 1). The participants in this group will undergo an initial consultation, anthropometry measurements, and laboratory tests, and will receive equipment for self-assessment during their first visit. Participants in this group collect data and will keep a food diary for review at their next visit.
Participants in the standard care group will have 3 visits (Table 1). These participants will not receive any equipment for self-assessment.
Self-Assessment Devices Used in the Study
Participants in the high- and low-intensity intervention groups will receive a tonometer (M6 Comfort Digital Tonometer; OMRON Healthcare, Kyoto, Japan), an activity monitor (HJA-405T; OMRON Healthcare), and a body composition monitor (BF214; OMRON Healthcare) for self-monitoring at home (see
Supplementary File 2). Before the equipment is given out, participants will be trained in how to use it and how to input information into the self-control diary.
Data Monitoring, Data Collection, and Providing Feedback
Study participants can choose the way they provide self-monitored data to the consulting physician from 3 options (Supplementary File 2). RJT18App is a smartphone application to promote behavior change through self-monitoring of BP, BW, and levels of physical activity.
The general procedures for data collection are shown in
Figure 1.
Self-monitoring data received from the high-intensity intervention group are analyzed by consultants once a week. The participants then consult with physicians using individual e-mails with support messages.
Self-monitoring data received from the low-intensity group are collected and analyzed by consultants after 3 and 6 months of follow-up during face-to-face visits.
Prevention Counseling
Details regarding prevention counseling are provided in
Supplementary File 3. On the first visit, the negative consequences of obesity are explained to all participants. Individual recommendations are based on personal characteristics and dietary assessments.
To assess participants’ actual diet and drinking regimen, specialists analyze participants’ diets over the 2–3 days before their first visit or over 2–3 days of a typical diet if the diet in the days before the first visit was atypical. A 24-h food questionnaire is used to collect this information. Food behavior is also investigated. Detailed instructions for dietary counseling have been prepared (Supplementary File 3) and all investigators were trained to provide this counseling.
Very detailed and precise goal setting to decrease calorie intake is provided to all participants.
The intervention includes the development of individual action plans for diet and physical activity for the entire study period, as well as for each week throughout the study period.
Statistical Analysis
Data collected will be located only in the NMRCTPM in Russia. Statistical analyses will be performed by statisticians in the NMRCTPM based on the statistical analysis plan. Intention-to-treat (ITT) analysis will be performed to construct analysis datasets.
The primary endpoints are: (1) the percentage change in BW from 0 to 3 and 6 months; and (2) the proportion of participants achieving a weight loss of >3% from their initial weight.
Secondary endpoints include obesity parameters, including BMI, WC (continuous), and the proportion of participants who lost ≥5% of their initial weight (binary), among others described in the statistical analysis plan (Supplementary File 4).
Primary endpoints will be analyzed using non-parametric Kruskal-Wallis or Wilcoxon tests or analysis of variance. The level of significance will be set to 1.7% based on the Bonferroni method for comparing 3 groups in the main analysis and to 0.05% for other analyses.
Sample Size
The sample size was calculated using the SAS version 9.4 (SAS Institute, Cary, NC, USA), based on the outcome variable “change in weight” of individuals. Under the settings of 90% power, a significance level of 1.7%, and a mean (±SD) difference among the 3 groups of 2±3 kg, a sample size of 150 individuals (n=50 in each group) was determined. Considering sample losses in the intervention groups, the final sample size was set to 200 individuals, 75 in each of the 2 intervention groups and 50 in the control group.
Ethical Considerations and Trial Registration
This study conforms to the ethical provisions of the Helsinki Declaration and the protocol was approved by the ethics committee of the NMRCPM (protocol 03–03/18 from 25/05/2018). This study is registered with the UMIN Clinical Trial Registry (ID: UMIN000033792).
