Clinical trial NCT06152588: Restricted Eating Time in the Treatment of Type 2 Diabetes
Official title: Restricted Eating Time in the Treatment of Type 2 Diabetes - the RESET2 Trial.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Type 2 Diabetes
Keywords: Time-restricted eating
Type 2 Diabetes
Obesity
Overweight
Fasting
Circadian rhythm
Lead sponsor: Steno Diabetes Center Copenhagen
Sponsor class: OTHER
Collaborators: name: University of Leeds
name: Salk Institute for Biological Studies
name: University of Copenhagen
name: Glostrup University Hospital, Copenhagen
First posted: 2023-11-30
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The overall aim of the present study is to investigate the effectiveness of implementing a 1-year time-restricted eating (TRE)-based intervention on glycaemic control, body weight and composition, cardiometabolic risk factors, and behaviour in individuals with overweight/obesity and type 2 diabetes (T2D).

Detailed description: In people with type 2 diabetes (T2D), weight loss is associated with improved glycaemic control and markers of cardiometabolic function as well as reduced use of antidiabetic medicine. Beyond pharmacological treatments, current strategies to reduce body weight and improve glycaemia include energy-restricted diets and increased physical activity.

Lifestyle interventions are complex, affecting many aspects of peoples' daily life. Dietary restrictions often result in rapid weight loss but the weight is gradually regained by many. Barriers to implement and maintain dietary changes include relapse of old habits and lack of knowledge, support, and insights into the type and amount of foods eaten. Previous lifestyle interventions targeting weight loss in T2D show efficacy for improving markers of metabolic and cardiovascular risk, including body weight and glycaemia during the intervention, but weight regain is often present. One reason may be that the intervention is not modified according to the needs of the target group. Often, weight loss interventions are shaped by a 'one size fits all' approach where both individual capabilities and motivation as well as social and contextual factors are more or less ignored. A user-based design could facilitate enrolment of participants and promote implementation and maintenance of the intervention among participants.

Intermittent fasting regimens have been suggested as efficient strategies for improving cardiometabolic health to a greater extent than can be attributed to the reduction in energy intake alone. TRE limits the time available for food intake to typically 8-10 hours/day without other dietary restrictions and has been put forward as a novel, acceptable, and safe strategy that has shown promising effects on body weight, glucose metabolism, appetite, and cardiometabolic health in individuals at high risk of T2D.

Although it has been suggested that TRE is a safe and feasible intervention, the longer-term effectiveness of TRE on glycaemic control and weight loss in individuals with T2D is unknown alongside the long-term acceptability and sustainability. Additionally, potential social and contextual challenges associated with integration of TRE into ordinary daily life structure and routines call for new approaches to support the individual in implementing and maintaining the strategy.

Overall, the RESET2 study consists of three phases; 1) Need assessment, 2) Pilot study, and 3) RCT. The aim of the present study (RCT) is to investigate the effectiveness of implementing a 1-year TRE-based intervention in individuals with overweight/obesity and T2D. Participants will attend 6 visits at Steno Diabetes Center Copenhagen (SDCC): Visit 0 (screening), Visit 1 (baseline, minimum 10 days after screening), Visit 2 (10 days prior to visit 3), Visit 3 \[3 months (12 weeks) after baseline\], Visit 4 (10 days prior to visit 5), Visit 5 \[12 months (52 weeks) after baseline\].

The specific objectives are:

1. To investigate the effect of a 1-year TRE intervention on changes in glycaemic control (HbA1c) in individuals with overweight/obesity and T2D.
2. To investigate the effects of a 1-year TRE intervention on changes in body weight, fat mass, continuous glucose monitoring (CGM) recorded time in range (TIR 3.9-10.0 mmol/l), and use of antidiabetic medication in individuals with overweight/obesity and T2D.
3. To describe changes in cardiometabolic risk factors (including fat-free mass, blood lipids, markers of kidney and liver function and inflammation, hormones involved in glucose metabolism and appetite control, liver fat, blood pressure, waist- and hip circumference), time below range (TBR), time above range (TAB), cognition, food preferences and reward, dim light melatonin onset (DLMO), and patient-reported outcomes including self-rated health, physical activity, well-being, diabetes distress, depression, food intake, and sleep quality.
4. To investigate the effects of a 3-month TRE intervention on changes in brain insulin sensitivity (sub-study).
5. To describe the extent to which the intervention was conducted as planned (visits, conversations, phone calls, peer support activities).
6. To describe the extent to which participants participated in support-related activities.
7. To explore participants' experiences with following TRE throughout a year including how they managed to keep their eating window and how the supporting activities and individualized approach worked for them (sub-population).
8. To explore the results from objectives 1-7 in relation to the extent the participants adhered to eating windows.

Eligibility criteria: Inclusion Criteria:

* Age: ≥18 years
* Overweight or obesity (BMI ≥25 kg/m2)
* T2D with HbA1c\>53 mmol/mol
* Habitual eating window ≥12 h/day (incl. foods/snacks and energy-containing beverages)

Exclusion Criteria:

* Bariatric surgery or planned bariatric surgery within study duration
* Use of fast acting insulin and combination insulin products
* Habitual CGM use
* A wish to adhere to Ramadan
* For women: current/planned pregnancy or lactation
* Alcohol or drug abuse (judged by investigator) or treatment with disulfiram
* Severe hypoglycaemia within last year (Severe hypoglycaemia, as defined by the American Diabetes Association (ADA), denotes severe cognitive impairment requiring external assistance for recovery)
* Inability to understand written and oral information in Danish
* Unable or unwilling to adhere to TRE; for instance, due to competing medical conditions.
* Medical condition which, based on investigators assessment, challenges participation including but not limited to severe heart, vascular or lung disease, cancer, chemotherapy, psychiatric, gastrointestinal, rheumatic, or endocrine diseases etc.
* Concomitant participation in other intervention study
* Inability to perform neuropsychological tests (e.g., severe vision and hearing impairment that can-not be improved with aids such as glasses and hearing aids, or language barrier.)

Exclusion criteria for the sub-study:

* Magnetic resonance imaging (MRI) contraindications based on the MR department's exclusion criteria including pacemaker or other implanted electronic devices, implanted metal objects not compatible to MRI scanning and severe claustrophobia
* Participants who do not wish to be informed about accidental findings by MR.

Primary outcomes:
measure: Change in HbA1c (mmol/mol)
timeFrame: Change from baseline to 3-months of intervention (strict TRE)
measure: Change in HbA1c (mmol/mol)
timeFrame: Change from baseline to the end of the intervention (12 months)
Secondary outcomes:
measure: Body weight (kg)
timeFrame: Change from baseline to end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Fat mass (kg)
timeFrame: Change from baseline to end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Time in range (% 3.9-10.0 mmol/l)
timeFrame: Change from baseline to end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Use of antidiabetic medication
timeFrame: Change from baseline to end of the intervention (12 months). Assessed at baseline, 3 months, 12 months.
Other outcomes:
measure: Body weight (kg)
timeFrame: Change from baseline to 3 months
measure: Height (m)
timeFrame: Measured only at screening
measure: Body mass index (kg/m^2)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Fat mass (kg)
timeFrame: Change from baseline to 3 months
measure: Time in range (% 3.9-10.0 mmol/l)
timeFrame: Change from baseline to 3 months
measure: Use of antidiabetic medication
timeFrame: Change from baseline to 3 months
measure: Change in overall medication use
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Blood lipids (mmol/l)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Fat free mass (kg)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Hormones-Insulin (pmol/L)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Hormones-Glucagon (pmol/L)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Hormones-C-peptide (pmol/L)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Hormones-Leptin (pmol/L)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Hormones-Fibroblast growth factor 21 (pmol/L)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Hormones-Glucagon-like peptide-1 (pmol/L)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Hormones-Glucose-dependent insulinotropic polypeptide (pmol/L)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Hormones-Ghrelin (pmol/L)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Hormones-Peptide YY (pmol/L)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Hormones-Neuropeptide Y (pmol/L)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Hormones-Growth differentiating factor 15 (pmol/L)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Marker of kidney function - Creatinine (µmol/L)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Marker of kidney function - eGFR (mL/min)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Plasma beta-hydroxybutyrate (mmol/L)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Marker of liver function - Aspartate-aminotransferase (U/L)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Marker of liver function - Alanine aminotransferase (U/L)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Marker of liver function - Thrombocytes (x10^9/L)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Markers of inflammation- Tumor necrosis factor alpha (pmol/L)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Markers of inflammation-Adiponectin (pmol/L)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Markers of inflammation-C-reactive protein (mg/L)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Markers of inflammation-Interleukin 6 (pmol/L)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Time Below Range (% <3.9 mmol/l)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Time Above Range (% >10.0 mmol/l)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Coefficient of variation (CV) of glucose concentrations
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Mean glucose concentrations
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Standard deviation of glucose concentrations
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Systolic blood pressure (mmHg)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Diastolic blood pressure (mmHg)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Resting heart rate (bpm)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Waist circumference (cm)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Hip circumference (cm)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Waist/hip ratio
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Degree of liver fibrosis (kPa)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Degree of liver steatosis (dB/m)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Food choice
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Attention
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Reaction time (ms)
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Explicit liking
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Explicit wanting
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Implicit wanting
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Self-reported binge eating disorder
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Self-reported physical activity
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Self-reported sleep quality
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Self-reported information on social relations and social support
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Self-reported sleepiness
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Self-reported eating behavior
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Self-reported night eating
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Self-reported food intake
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Self-reported diabetes distress
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Self-reported sexual functioning/well-being
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Self-reported mood
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Self-assessed questionnaire to determine morningness-eveningness in human circadian rhythm
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Subjective appetite
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Cognition
timeFrame: Change from baseline to 3 months and from baseline to the end of the intervention (12 months). Measured at baseline, 3 months, 12 months
measure: Dim light melatonin onset (DLMO) (subgroup only)
timeFrame: Change from baseline to 3 months. Measured at baseline and 3 months
measure: Brain insulin resistance (subgroup only)
timeFrame: Change from baseline to 3 months. Assessed at baseline and 3 months.
measure: Adherence (%)
timeFrame: Registered 2 days/week on random days via an online questionnaire.
measure: Degree of participants' participation in intervention activities - Visits
timeFrame: Visit 1, visit 2, visit 3, visit 4, visit 5
measure: Degree of participants' participation in intervention activities - Conversations
timeFrame: Conversations at visit 1 and visit 3
measure: Degree of participants' participation in intervention activities - Peer support group meetings
timeFrame: Support group meetings will be held once monthly
measure: Degree of participants' participation in intervention activities - Phone calls
timeFrame: Phone calls after 2, 6, 9 weeks + Phone calls after 6 and 9 months
measure: Participants' acceptance of TRE
timeFrame: The interviews will be conducted at the end of intervention (1 year after baseline) at visit 5
measure: Energy intake (kJ)
timeFrame: Registrations prior to baseline (visit 1), after 3 months (visit 3), and after 12 months (visit 5)
measure: Fat energy percent
timeFrame: Registrations prior to baseline (visit 1), after 3 months (visit 3), and after 12 months (visit 5)
measure: Carbohydrate energy percent
timeFrame: Registrations prior to baseline (visit 1), after 3 months (visit 3), and after 12 months (visit 5)
measure: Protein energy percent
timeFrame: Registrations prior to baseline (visit 1), after 3 months (visit 3), and after 12 months (visit 5)
measure: Alcohol energy percent
timeFrame: Registrations prior to baseline (visit 1), after 3 months (visit 3), and after 12 months (visit 5)
measure: Dietary fibers (gram)
timeFrame: Registrations prior to baseline (visit 1), after 3 months (visit 3), and after 12 months (visit 5)
Locations:
city: Herlev
country: Denmark
facility: Steno Diabetes Center Copenhagen
Study officials:
affiliation: Steno Diabetes Center Copenhagen
name: Jonas S Quist, PhD
role: PRINCIPAL_INVESTIGATOR
References: