Dietary Strategies for Remission of Type 2 Diabetes

NCT ID: NCT04943926

Last Updated: 2022-07-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 600 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-04
• Study Completion Date: 2040-12-31

Brief Summary

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.

Detailed Description

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.

The study will enroll eligible participants to the study continuously, until the total number of participants needed for the study is reached. Each participant will follow their own timeline, and attend visits at the study center at baseline, 3, 9 and 15 months.

During 2 weeks before each visit, participants will wear a continuous glucose monitor (CGM) and record food intake for at least 3 consecutive days during this period.

Measurements during visits will include anthropometric variables/body composition and energy expenditure, blood, saliva, urine and stool samples will be collected, and participants will be asked to fill out questionnaires on physical activity, sleep pattern, meal frequency, quality of life, problem areas in diabetes, eating efficacy and eating behaviors. They will also have a consultation with a registered dietitian and meet with the study medical doctor when needed.

A blinded statistician will perform the statistical analyses for the primary outcome of the study.

Conditions

Diabetes Mellitus, Type 2; Overweight and Obesity; Hypertension; Glucose Intolerance; Insulin Resistance; Dyslipidemia Associated With Type II Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Energy Restricted Diet

A nutritional complete formula diet for 3 months followed by an energy restricted diet for 12 months.

Group Type: ACTIVE_COMPARATOR

Energy restricted diet

Intervention Type: OTHER

Nutritional complete formula diet followed by an energy restricted diet

Continuous LCHF Diet

A very low-carbohydrate high-fat ketogenic diet (VLCHF) diet for 3 months, followed by a low-carbohydrate high-fat diet (LCHF) for 12 months.

Group Type: EXPERIMENTAL

Low carbohydrate high fat diet

Intervention Type: OTHER

Very low-carbohydrate high-fat ketogenic diet (VLCHF) diet followed by a low-carbohydrate high-fat diet (LCHF)

Interventions

Energy restricted diet

Nutritional complete formula diet followed by an energy restricted diet

Intervention Type: OTHER

Low carbohydrate high fat diet

Very low-carbohydrate high-fat ketogenic diet (VLCHF) diet followed by a low-carbohydrate high-fat diet (LCHF)

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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)

Exclusion Criteria

• 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

• Minimum Eligible Age: 24 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Karolinska Institutet

OTHER

Sponsor Role: collaborator

University of Glasgow

OTHER

Sponsor Role: collaborator

University of Copenhagen

OTHER

Sponsor Role: collaborator

Technical University of Munich

OTHER

Sponsor Role: collaborator

University of Bergen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Department of Clinical Science

Bergen, Vestland, Norway

Site Status: RECRUITING

Countries

Norway

Central Contacts

Simon N Dankel, PhD

Role: CONTACT

Simon.Dankel@uib.no

+4794308637

Kristin Amundsen, MSc

Role: CONTACT

k.amundsen@uib.no

+4797171257

Facility Contacts

Pål R Njølstad

Role: primary

Pal.Njolstad@uib.no

+47 55 97 51 53

Other Identifiers

CARBCOUNT Multicenter RCT

Identifier Type: -

Identifier Source: org_study_id