The PROMOTE study (High Protein and Resistance training Combination in Overweight and Obesity) is an 8-week randomized parallel controlled trial followed by a 24-week observational follow-up study. A 48-week supplementary follow-up study will be carried out if necessary. The enrolled participants will be randomly assigned to the conventional low-fat diet group, the high-protein diet group and the high-protein diet and resistance training combination group, and changes in body weight, body fat and metabolic indexes will be compared between the three groups in the short term (8 weeks), the medium term (24 weeks) and the long term (48 weeks). The efficacy of the high protein and conventional low-fat diets on weight loss, fat loss and improvement of various metabolic indexes will be evaluated, and compared with the efficacy of the resistance training and high-protein diet combination. After 8 weeks of intervention, the participants will be strongly recommended to continue their diet and exercise plans until the achievement of individualized weight loss goal. During the following 24 or 48 weeks of observation, the participants’ diet management knowledge will be tested, their self-efficacy evaluated, and the proportion who continued to adhere to the plans will be observed. Finally, the relationship between diet management knowledge, self-efficacy and weight loss will be explored. (Figure 1)
The inclusion criteria will be 18–50 years old, either obese or overweight [body mass index (BMI) between 24.0 and 32 kg/m2), and strongly willing to lose weight. Participants also will have to agree to participate and sign the informed consent form.
The exclusion criteria will be: 1. Pregnant women; 2. Anyone with severe cardiopulmonary disease that cannot tolerate resistance training (cardiac function of grade III/IV); 3. Anyone with diabetes, uncontrolled hypertension, recent acute infectious diseases or cancer; 4. Anyone who drank excessively or had drunk heavily more than twice a week in the last month; 5. Anyone with kidney disease or renal insufficiency (eGFR < 90 mL/min/1.73 m2); 6. Anyone who had stopped smoking in the past 6 months or had a recent plan to do so; 7. Anyone with hypothyroidism, Cushing’s syndrome, or polycystic ovary syndrome; 8. Anyone with mental health problems such as severe depression; 9. Anyone who was unable to cooperate or to complete the study because of any other reason; and 10. Anyone who had participated in another clinical study in the previous 3 months.
After successful enrollment, the participants will have a one-week (± 2 days) run-in period, during which they will be required to record their diet and exercise using the application MyFitnessPad on a daily basis. Their compliance will be assessed against this record and participants with poor compliance in the run-in period will not be allowed to continue to participate.
After the run-in period, the participants will be randomly assigned to the high-protein diet and resistance training combination group (n = 30), the high-protein diet group (n = 30) and the conventional low-fat diet control group (n = 30) in a 1:1:1 ratio. The high-protein diet group will consume 900–1700 kcal per day, with 25-35% carbohydrate, 30-40% protein and 30-40% fat, and their daily protein intake per kilogram of fat-free mass was 1.5–2.0 g. The conventional low-fat diet group will also consume 900–1700 kcal per day, but the proportion of carbohydrate, protein and fat was 50-60%, 15-20% and 25-30%, and their daily protein intake per kilogram of fat-free mass was 0.8–1.2 g. The detail of the resistance training is shown in the Appendix. All participants will take part in aerobic exercise as a background intervention, because of its necessity in weight loss. Similarly, because of the importance of dietary intervention in weight loss, the study does not include a group who just do resistance training without any dietary intervention.
The participants’ baseline data will be collected, including body weight, body fat percentage and fat-free mass (using Tanita TBF-300A Body Composition Analyzer, Tanita Europe, UK), waist circumference, hip circumference, systolic and diastolic blood pressure (Omron sphygmomanometer, Omron Healthcare Limited, Milton Keynes, UK), and a blood sample for the determination of blood glucose, blood lipids, renal function and insulin level. These will be collected in the morning after an 8-hour fast.
During the 8-week intervention, the participants will receive dietary guidance, which varied by group, and prepare their own food following advice from the dietitian. Participants in the resistance training group have to take part in resistance training at least three times a week. During the 8 weeks, the participants will receive face-to-face visits in the 2nd, 4th and 6th weeks, and their body weight, waist circumference, hip circumference, and systolic and diastolic blood pressure will be measured during each visit. The participant will receive telephone calls during the 1st, 3rd, 5th and 7th weeks. During both visits and telephone calls, dietary and exercise guidance will be provided and recorded, and the MyFitnessPad diet inputs will be checked and recorded in written case report forms. The participants will also receive a face-to-face visit at the end of the 8-week intervention, and their body weight, body fat percentage and fat-free weight, waist circumference, hip circumference, and systolic and diastolic blood pressure will be measured, and blood samples taken for the determination of blood glucose, blood lipids, renal function and insulin levels. The participants’ self-efficacy will be investigated using the generalized self-efficacy scale (GSES) , and the diet management knowledge will be evaluated using a self-designed questionnaire.
During the intervention period, the participants will not be allowed to add anything to their agreed intake (such as snacks and drinks) or to change their diet. If the participants wish to change their main meal for a particular reason (such as a social event), the investigator will be consulted by telephone to decide on the remedial measures required (such as reduction of calorie intake the next day). Any changes will be recorded using the MyFitnessPad record.
During the follow-up period, participants will be no longer required to continue with their diet and training plan, although this will be strongly recommended by the investigators until the achievement of individualized weight loss goal. The participants will receive a telephone follow-up every 4 weeks, where their body weight and waist circumference will be measured by the participants themselves and recorded by the investigators. Face-to-face visits will be also carried out at the end of the 24-week observation period. Body weight, body fat percentage and fat-free mass, waist circumference, hip circumference, and systolic and diastolic blood pressure will be measured, diet will be investigated, and blood samples will be taken for the determination of blood glucose, blood lipids, renal function and insulin levels.
During the baseline period and throughout the trial, the participants will be asked to maintain a flexible diet, pay attention to the type, quantity and weight of their food and liquid intake, and use the smartphone application MyFitnessPal to record their daily diet in detail. This is a reliable way to track diet [25-27]. Throughout the study, the investigators will use WeChat, telephone or MyFitnessPad to monitor and guide the participants on diet and training, ensure strict compliance with plans, and provide extra guidance to anyone with poor compliance. Participants with poor compliance will be allowed to continue to participate, but warned about the importance of compliance. Diet will be evaluated using professional diet analysis software Nutritics (Nutrictics Ltd., Co Dublin, Ireland). The participants’ daily calorie intake will be assessed using the Katch-McArdle formula (1996), which is based on the resting daily energy expenditure [RDEE; 370 + (21.6 × lean body weight in kg)], and adjusted for exercise needs and non-exercise adaptive heat generation . The calorie intake assessment will ensure that participants have a negative calorie balance of 500–700 kcal per day during the study period, so the daily recommended energy intake (kcal) will be 1.2 (or 1.3) × RDEE − 500 (or 700). Daily protein intake in the high-protein diet group = fat-free mass × 1.5–2.0 (g), and the daily protein intake in the conventional protein diet group = fat-free mass × 0.8–1.2 (g).
Primary outcome: body weight changes at week 8 and week 24 compared with the baseline level.
- The body fat percentage changes at weeks 8 and 24 compared with the baseline level.
- The waist circumference changes at weeks 8 and 24 compared with the baseline level.
- The proportion of participants who have successfully lost weight and been non-obese (defined as BMI < 24 kg/m2) at week 8 and 24.
- Diet management ability and weight loss perseverance at weeks 8 and 24.
- The self-efficacy changes at weeks 8 and 24 compared with the baseline level.
- Compliance with the original diet plan at weeks 8 and 24.
- The fasting blood glucose changes at weeks 8 and 24 compared with the baseline level.
- The fasting insulin level changes at weeks 8 and 24 compared with the baseline level.
- Blood pressure changes at weeks 8 and 24 compared with the baseline levels.
- Incidence of adverse events.
Body weight is the primary outcome of this study, and is selected as the main variable. Some important secondary variables with clinical significance are also selected for evaluation. Examinations conducted at each visit are shown in Table 1.
Randomization and allocation concealment mechanism
The stratified block randomization method will be used. Participants will be stratified by research center, and the appropriate segment lengths will be selected. Based on the number of seeds, a random coding table of 90 participants will be generated using the statistical software SAS8.2 PROC PLAN by the third party (Zhijun Tan and Lei Shang). The randomized sequential numbers will be segmented, retained in the research centers, and managed by the third party (Zhijun Tan and Lei Shang) who will not be involved in the data collection. The investigators (Shaoyong Xu, Juan Zhang, Ruikun Chen and Wenlei Xu) will enroll participants. When needed, the investigator (Shaoyong Xu) will ask for numbers from the third party by telephone, using the order in which the participants will be treated, and assign participants to the intervention scheme with that serial number provided.
This is an open label study with only laboratory personnel and data analysts (the third party: Zhijun Tan and Lei Shang) being blinded. Also, unblinding will not occur.
Epidata 3.1 (The EpiData Association, Odense Denmark) will be performed to manage data and double data entry will be used to promote data quality. The primary and secondary outcomes will be analyzed based on the full analysis set (FAS). All outcomes will also be analyzed based on the per protocol set (PP). The security endpoint will be analyzed based on the safety analysis set (SS). Supportive sensitivity analysis will be carried out based on the PP and FAS, using the method of last observation carried forward. Descriptive analysis will be conducted for continuous variables such as body weight, body fat percentage, blood glucose, blood lipids and blood pressure. Indexes such as the percentage of participants achieving effective weight loss will be summarized using frequencies and percentages. The adverse events and their incidence will be summarized. The mid-term analysis will be carried out at the end of the intervention, before the follow-up study.
Determination of sample size
This study is an exploratory pilot study. In line with previous studies [18,23], 30 participants in each group were initially scheduled to evaluate the efficacy of each group, and whether more participants should be included or the study should be stopped.