A Feasibility Study of Optimal Non-Pharmacological Lifestyle Modifications in People With Type 2 Diabetes

NCT ID: NCT07262788

Last Updated: 2025-12-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-30
• Study Completion Date: 2027-03-31

Brief Summary

The overall aim of this study is to examine the feasibility of a 12-month, two-arm lifestyle intervention to induce and maintain remission of type 2 diabetes (T2D). The findings from the feasibility study will inform the recruitment, design and delivery of the interventions in a 5-arm, 24-month randomised controlled trial.

Detailed Description

Studies on T2D remission have reported varying rates of remission, often around 50% in intervention groups. These studies typically involve individuals with a recent T2D diagnosis, usually within six to ten years of diagnosis, with intervention periods most commonly lasting between twelve and twenty-four months, though durations have ranged from six to sixty months. Lifestyle interventions combining dietary changes and increased physical activity generally yield modest remission rates, but maintaining adherence over time remains challenging. Trials that include an initial phase of a very low-calorie diet, followed by ongoing structured support, tend to report higher remission rates. This emphasizes the critical role of significant and sustained weight loss. However, the most effective combination of dietary, exercise, and behavioral support strategies remains to be determined.

In addition to calorie restriction, changes in dietary composition may influence the underlying mechanisms of T2D. For instance, reducing carbohydrate intake can promote ketone production, affecting liver glucose production and improving glycemic control. Higher protein intake has been linked to an improved insulin response. Replacing saturated fats with polyunsaturated fats and increasing dietary fiber may also support glucose metabolism. However, it remains unclear whether carbohydrate-reduced or carbohydrate-rich diets are more effective in supporting long-term remission following initial weight loss.

Physical activity, particularly high-intensity exercise, plays a key role in reducing the risk of T2D, supporting weight management, and improving remission rates when combined with dietary interventions. Significant improvements in blood glucose control are usually seen with regular moderate-to-high-intensity exercise.

Moreover, there is considerable variation-or sometimes an absence-in the inclusion of key lifestyle intervention components, such as specific dietary and exercise protocols, as well as levels of supportive activities. This inconsistency complicates effective care provision for healthcare professionals and makes it difficult for individuals with T2D to adhere to non-pharmacological management recommendations.

Despite the known benefits of lifestyle modifications, initiating and maintaining these changes is challenging due to barriers such as a lack of support, motivation, and knowledge about nutrition and portion sizes. Involving individuals with T2D in designing and evaluating interventions may improve adherence, reduce participant burden, and increase the feasibility and scalability of lifestyle programs for wider implementation.

The overall aim of this study is to examine the feasibility of a 12-month, two-arm intervention designed to induce and maintain remission of T2D. After baseline measurements, participants will be randomized to one of two groups: Group A: Very-low-calorie-diet (VLCD)/weight loss followed by a carbohydrate-reduced (CH-reduced) diet combined with high-intensity exercise. Group B: VLCD/weight loss followed by a carbohydrate-rich (CH-rich) diet combined with high-intensity exercise. Participants will be blinded to the intervention arm during the VLCD phase. To determine the optimal macronutrient composition of the Mixed Meal Tolerance Test (MMTT) for subsequent testing, participants will attend three MMTTs in random order at baseline. The MMTTs consists of three different macronutrient compositions (X energy percentage (E%)carbohydrate, XE% protein, XE% fat; XE% carbohydrate, XE% protein, XE%fat; E% carbohydrate, XE% protein, XE% fat)

Feasibility will be evaluated based on the recruitment process, intervention acceptability, and participant adherence. This includes assessing whether the intervention components and outcome measurements are delivered and conducted as intended. Additionally, the study will examine how these elements perform in a real-life setting among individuals with T2D. Findings from this feasibility study will inform recruitment strategies, study design, and implementation of a subsequent five-arm, 24-month randomized controlled trial.

Specific aims:

1. To study the recruitment process (including recruitment of general practitioners and participants) and identify related barriers and facilitators.

2. To investigate retention, adherence, and acceptability of the interventions (carbohydrate-reduced or carbohydrate-rich diet combined with high-intensity exercise), including participant experiences with the intervention components and data collection procedures.

3. To assess whether the intervention is delivered as intended, covering supervised/unsupervised sessions, study visits, online support, and group education.

4. To evaluate the effectiveness of safety procedures in responding to changes in participants' glycemic control, blood pressure, physical injuries, and related risk markers.

5. To determine the optimal macronutrient composition and sampling schedule for the Mixed Meal Tolerance Test (MMTT).

6. To explore the potential impact of the two interventions on T2D remission rates and related metabolic outcomes such as body weight, body composition, blood pressure, vascular function, glycemic control, lipid profile, beta-cell function, and inflammation.

Conditions

Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CH-rich diet with exercise

A CH-rich diet combined with an exercise programme (n=12)

Group Type: EXPERIMENTAL

CH-rich diet with exercise

Intervention Type: OTHER

After 12 weeks of following a VLCD (Phase 1), participants begin a 6-week transition (Phase 2). During this phase, they adopt a CH-rich diet, consuming 50-55% of their total energy from carbohydrates. This involves shifting gradually but structurally from formula products to regular meals. Meal boxes and formula products aligned with their assigned diet support this shift and serve as educational tools. Phase 2 also includes an exercise program consisting of two supervised 1-hour sessions and one 1-hour unsupervised high-intensity session weekly (intensity \>70% peak oxygen uptake (VO2peak) and/or \>7 on the Rate of Perceived Exertion scale (RPE), equivalent to 1-3 repetitions in reserve for resistance training or vigorous intensity). For the next 34 weeks (Phase 3), participants receive ongoing diet and exercise support while purchasing and preparing their own meals according to their assigned diet. They continue with two supervised and one unsupervised group session per week.

CH-reduced diet with exercise

A CH-redcued diet combined with an exercise programme (n=12)

Group Type: EXPERIMENTAL

CH-reduced diet with exercise

Intervention Type: OTHER

After 12 weeks of following a VLCD (Phase1), participants begin a six-week transition (Phase 2 ). During this phase, they adopt a CH-reduced diet, consuming 25-30% of their total energy from carbohydrates. This involves shifting gradually but structurally from formula products to regular meals. Meal boxes and formula products aligned with their assigned diet support this shift and serve as educational tools. Phase 2 also includes an exercise program consisting of two supervised 1-hour sessions and one 1-hour unsupervised high-intensity session weekly (intensity \>70% peak oxygen uptake (VO2peak) and/or \>7 on the RPE scale, equivalent to 1-3 repetitions in reserve for resistance training or vigorous intensity). For the next 34 weeks (Phase 3), participants receive ongoing diet and exercise support while purchasing and preparing their own meals according to their assigned diet. They continue with two supervised and one unsupervised group session peer week.

Interventions

CH-rich diet with exercise

After 12 weeks of following a VLCD (Phase 1), participants begin a 6-week transition (Phase 2). During this phase, they adopt a CH-rich diet, consuming 50-55% of their total energy from carbohydrates. This involves shifting gradually but structurally from formula products to regular meals. Meal boxes and formula products aligned with their assigned diet support this shift and serve as educational tools. Phase 2 also includes an exercise program consisting of two supervised 1-hour sessions and one 1-hour unsupervised high-intensity session weekly (intensity \>70% peak oxygen uptake (VO2peak) and/or \>7 on the Rate of Perceived Exertion scale (RPE), equivalent to 1-3 repetitions in reserve for resistance training or vigorous intensity). For the next 34 weeks (Phase 3), participants receive ongoing diet and exercise support while purchasing and preparing their own meals according to their assigned diet. They continue with two supervised and one unsupervised group session per week.

Intervention Type: OTHER

CH-reduced diet with exercise

After 12 weeks of following a VLCD (Phase1), participants begin a six-week transition (Phase 2 ). During this phase, they adopt a CH-reduced diet, consuming 25-30% of their total energy from carbohydrates. This involves shifting gradually but structurally from formula products to regular meals. Meal boxes and formula products aligned with their assigned diet support this shift and serve as educational tools. Phase 2 also includes an exercise program consisting of two supervised 1-hour sessions and one 1-hour unsupervised high-intensity session weekly (intensity \>70% peak oxygen uptake (VO2peak) and/or \>7 on the RPE scale, equivalent to 1-3 repetitions in reserve for resistance training or vigorous intensity). For the next 34 weeks (Phase 3), participants receive ongoing diet and exercise support while purchasing and preparing their own meals according to their assigned diet. They continue with two supervised and one unsupervised group session peer week.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Diagnosis of T2D and treatment with lifestyle and/or oral anti-diabetic medication and/or glucagon-like peptide-1 receptor agonists (GLP-1RAs)
• HbA1c between 36-86 mmol/mol
• T2D duration of ≤6 years
• BMI ≥27 kg/m2
• Body weight changes over 3 months ≤3 kg

Exclusion Criteria

• Insulin treatment within 6 months prior to screening (any type)
• Heart failure (ejection fraction<40%) and treated with SGLT-2i (current or planned)
• Kidney disease (eGFR<60 ml/min) and treated with SGLT-2i (current or planned)
• Physical comorbidity, which precludes the physical activity during intervention
• Dietary restrictions or allergies making the participant unable adhere to the dietary interventions
• Unable to comply with trial procedures and/or interventions
• Alcohol/drug abuse
• Planned or present pregnancy
• Unstable psychiatric disease
• Diagnosed with binge eating disorder
• Participation (present or planned) in other clinical trials including lifestyle or pharmacy trials for any condition
• If HbA1c ≥60 mmol/mol and the participant is on 2 or more anti-diabetic drugs a positive GAD65 and/or stimulated C-peptide <800 pM excludes the patient

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Steno Diabetes Center Aarhus (SDCA), Aarhus University Hospital

UNKNOWN

Sponsor Role: collaborator

Steno Diabetes Center Odense

OTHER

Sponsor Role: collaborator

University of Copenhagen

OTHER

Sponsor Role: collaborator

The Novo Nordisk Foundation Center for Basic Metabolic Research

OTHER

Sponsor Role: collaborator

Bispebjerg Hospital

OTHER

Sponsor Role: collaborator

Steno Diabetes Center Copenhagen

OTHER

Sponsor Role: lead

Responsible Party

Jonas Salling Quist

Senior Researcher and Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jonas Salling Quist Senior Researcher and Associate Professor, PhD

Role: PRINCIPAL_INVESTIGATOR

Steno Diabetes Center Copenhagen, University of Copenhagen - Department of Biomedical Sciences

Locations

Steno Diabetes Center Copenhagen

Herlev, Denmark, Denmark

Site Status: RECRUITING

Countries

Denmark

Central Contacts

Jonas Salling Quist Senior Researcher and Associate Professor, PhD

Role: CONTACT

jonas.salling.quist@regionh.dk

+45 26176064

Anne-Ditte Termannsen Project Manager, PhD

Role: CONTACT

anne-ditte.termannsen@regionh.dk

+4551209970

Facility Contacts

Jonas Salling Quist Associate Professor, PhD

Role: primary

jonas.salling.quist@regionh.dk

+45 26176064

Other Identifiers

1-10-72-77-25

Identifier Type: -

Identifier Source: org_study_id