Dietary Strategies for Remission of Type 2 Diabetes - a Randomized Controlled Trial (CARBCOUNT)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 600
- 试验地点
- 2
- 主要终点
- Diabetes remission
研究概览
简要总结
In this project, the investigators will perform a multicenter randomised controlled trial to determine whether advice to consume a moderate, whole food-based low-carbohydrate high-fat (LCHF) ad libitum diet (CarbCount program) can produce and maintain equal remission rates of type 2 diabetes (T2D) as a nutritionally complete very-low-calorie formula diet followed by a energy-restrictive (i.e., calorie counting) diet (DiRECT principles). Within the principles of each approach, the dietary goals and change will be adjusted according to individual needs/capabilities conducive to long-term adherence. Furthermore, the investigators aim to determine whether the rate of diet-induced remission is reflected in/can be predicted by baseline or diet-induced changes in glucose variability (e.g., time-in-range measured by continuous glucose monitoring) and other factors such as anthropometric changes and genetic susceptibility. Each center will also conduct locally-lead standalone mechanistic research, including analyses of intra-abdominal/hepatic fat accumulation, adipose tissue biopsies and/or measurements of energy metabolism. Additionally, changes in medication use, nutritional status, cardiovascular disease risk, as well as adverse events, will be monitored.
详细描述
At least 588 patients with T2D will be recruited, approximately 120-150 men and women at each research center. The participants will be randomised to 1) a nutritional complete formula diet for 3 months followed by an energy restricted diet for 12 months or 2) a very low-carbohydrate high-fat (VLCHF) diet for 3 months, followed by a low-carbohydrate high-fat diet (LCHF) for 12 months. Each of the diets will cover all basic requirements for essential nutrients including amino acids, fatty acids, vitamins and minerals. Participants will be encouraged to consume at least 200 g of vegetables per day. Furthermore, we will emphasize high-quality, minimally processed foods. In arm 2 they will receive advice to eat specific fat sources such as extra virgin olive oil, butter and high-fat cheeses.
The DiRECT trial showed remission in 46% of participants after 12 months. Assuming that both the DiRECT program and LCHF dietary strategies yield a 45% chance of T2D remission after 15 months, it is calculated (using nQuery v8) that each group needs 235 participants to complete the trial. This sample size yields 90% statistical power to conclude, with respect to the primary outcome, whether the CarbCount Program is no more than 15% more or less effective than the DiRECT principles (equivalence study, one-sided p-value at 0.025). To allow for expected loss to follow-up (estimated at 20%), each of the arms needs at least 294 participants for a total of 588.
Participants will have access to electronic platforms that include an online database of recipes (breakfast, easy-to-cook lunches, snacks, dinners, and food for special occasions). The platforms will facilitate planning of week menus, and include an e-learning course covering topics such as how to cook and prepare foods, meal planning, dining out, sleep and individual aspects that challenge habit change. If the participants are failing in their efforts to establish or maintain lifestyle change, they will be encouraged to seek possible solutions in the e-learning courses or to contact one of the study's health educators and/or dietitians. Specific rescue plans involving direct contact with study staff will be implemented if a participant regains more than 2 kg or experiences T2D relapse.
After individual assessment by a doctor, the participants will be taken off diabetes medication upon starting the diet, and be asked to self-monitor blood sugar changes during the first 2 weeks on the diet, followed by a consultation that includes evaluation of these changes. The need of reintroduction of medication will be done in consultation with the study doctor at least every 3 months.
Between visits, the participants will complete dietary assessments and an e-learning course, and at least once a month have follow-ups with dietitians/health educators and/or online group workshops.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
We will use an independent statistician who will analyse the data anonymously and be blinded to information regarding dietary arms.
入排标准
- 年龄范围
- 24 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HbA1c ≥48 mmol/mol (with or without medical treatment)
- •Less than 10 years since the diagnosis of T2D
- •BMI ≥27 kg/m2 (≥25 kg/m2 for Asians)
排除标准
- •Treatment with insulin >25 IU
- •HbA1c concentration of 12% or more (≥108 mmol/mol)
- •Insulin to C-peptide ratio <0.8 (indicative of insulin deficiency)
- •Myocardial infarction within the previous 6 months, and severe or unstable heart failure or other severe diseases including cancer, psychiatric/eating disorders, severe depression and substance abuse
结局指标
主要结局
Diabetes remission
时间窗: 15 months
Number of patients with diabetes remission, defined as no use of glucose-lowering drugs and HbA1c \<48 mmol/mol (\<6.5%) at 15 months
次要结局
- Diabetes remission without anti-diabetes medications(3, 9 and 15 months)
- Changes in fasting insulin and insulin C-peptide concentrations from baseline(3, 9 and 15 months)
- Changes in eating self-efficacy (Three-Factor Eating Questionnaire, TFEQ)(3, 9 and 15 months)
- Changes from baseline in the frequency of diabetes- and antihypertensive medication usage(3, 9 and 15 months)
- Changes in quality of life(3, 9 and 15 months)
- Changes in eating behaviour from baseline and throughout the study(3, 9 and 15 months)
- Changes in HbA1c and fasting glucose concentrations from baseline(3, 9 and 15 months)
- Changes in estimated insulin resistance and beta cell function from baseline(3, 9 and 15 months)