Clinical trial NCT03854656: Effect of Time-restricted Eating on Behaviour and Metabolism in Overweight Individuals at High Risk of Type 2 Diabetes
Official title: Effect of Time-restricted Eating on Behaviour and Metabolism in Overweight Individuals at High Risk of Type 2 Diabetes - the RESET Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Overweight and Obesity
PreDiabetes
Keywords: Overweight
Obesity
Time-restricted eating
Prediabetes
Lead sponsor: Steno Diabetes Center Copenhagen
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
name: Aalborg University Hospital
name: IMotions A/S
name: University of Leeds
name: Salk Institute for Biological Studies
First posted: 2019-02-26
Enrollment: 100
Sex: ALL
Minimum age (years): 30
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled trial
Primary purpose: PREVENTION

Brief summary: The aim of the present study is to investigate effects of 12 weeks time-restricted eating on behaviour and metabolism in individuals with overweight or obesity at high risk of type 2 diabetes.

Detailed description: Overweight and obese individuals with pre-diabetes or with a family history of diabetes or cardiovascular disease (CVD) are at high risk for developing type 2 diabetes (T2D) and CVD. Current prevention and treatment of obesity and T2D include energy restricted diets and increased levels of physical activity; however, adequate adherence to such strategies is difficult, and maintenance is challenging for most individuals, which stresses the need for feasible and sustainable interventions.

Circadian rhythms of behaviour and metabolism are closely related to the daily light/dark cycle and sleep-wake patterns and timing of food intake and fasting periods may affect the circadian rhythms of metabolic organs. In an evolutionary perspective, the pattern of food consumption has been characterised by periods of caloric intake when food was available and subsequent periods of fasting 9. This cyclic pattern leads to cycles of absorption and storage of energy and utilisation of the energy for e.g. tissue repair, stress resistance and vitality where expression of metabolic regulators coordinates with cellular processes, leading to efficient metabolism 10. Factors including the 24-hour availability of energy-dense foods, busy time schedules, different eating and sleep patterns during weekdays and weekends (i.e. 'social jetlag') challenge the feeding-fasting paradigm. Recent data suggest that an erratic diurnal eating pattern characterised by food intake largely spread throughout hours awake (≥15 h) and a concomitant short fasting period is highly prevalent in humans and animal suggest that circadian misalignment of food intake is associated with adverse metabolic effects. A number of animal studies and a few small studies in humans have reported promising effects of time-restricted eating (TRE), without concomitant dietary restrictions, on body weight and other cardiometabolic risk factors. There is a lack of randomized controlled trials investigating effect of TRE in individuals at high risk of type 2 diabetes and cardiovascular diseases.

The aim of the present study is to investigate effects of 12 weeks TRE on behaviour and metabolism in individuals with overweight or obesity at high risk of type 2 diabetes. Maintenance will be assessed at a follow-up visit 13 weeks after completion of the trial (26 weeks). Testing will be conducted at baseline and after 6, 12, and 26 weeks. Participants are instructed to follow randomization during one week assessment periods after testing at 6 and 12 weeks. Therefore, the total duration of the intervention is 13 weeks.

Eligibility criteria: Inclusion Criteria:

* BMI ≥30 kg/m2 or BMI ≥25 kg/m2 in combination with pre-diabetes (HbA1c ≥39-\<48 mmol/mol)
* Habitual eating/drinking window ≥12 hours (including foods/snacks and energy containing beverages e.g. soft drinks (except of water)) and an eating/drinking window of ≥14 hours minimum one day per week

Exclusion criteria

* Daily smoking
* For women: pregnancy, planned pregnancy (within the study period) or lactating
* Frequent travels over time zones (max one return trip/travel over times zones (˃one hour time difference) during the 13 weeks intervention).
* Shift work or partner engaged in shift work (if it affects the person's sleep and eating pattern)
* Unable to understand the informed consent and the study procedures
* Self-reported history of an eating disorder during the past three years
* Self-reported weight change (\>5 kg) within three months prior to inclusion
* Diabetes
* HbA1c ≥48 mmol/mol
* Uncontrolled medical issues including but not limited to cardiovascular pulmonary, rheumatologic, hematologic, oncologic, infectious, gastrointestinal or psychiatric disease; diabetes or other endocrine disease; immunosuppression
* Current treatment with medication or medical devices which significantly affect glucose metabolism, appetite, or energy balance
* Current treatment with antidepressants
* Bariatric surgery
* Implanted or portable electro-mechanical medical device such as a cardiac pacemaker, defibrillator or infusion pump
* Celiac disease, Crohn's disease, ulcerative colitis or proctitis
* Alcohol/drug abuse or in treatment with disulfiram at time of inclusion
* Concomitant participation in other intervention studies
* Not able to eat ≥85% of the test meal because of e.g. allergy

Specific exclusion criteria for participants receiving SmartPillTM (n=60)

* Gastrointestinal symptoms or diseases such as regular (weekly) abdominal pain, dysphagia, gastric bezoars, strictures, fistulas, bowel obstructions or diverticulitis
* Current treatment with medication or medical devices which significantly affect gastrointestinal motility or transit time (prokinetics, antidiarrheals, laxatives, or opioids)
* Gastrointestinal surgery within 3 months before inclusion

Primary outcomes:
measure: Change in body weight (kg)
timeFrame: Change from baseline to the end of the intervention (after 12 weeks)
Secondary outcomes:
measure: Body weight (kg)
timeFrame: Changes from baseline. Fasted state at all four visits (Baseline and after 6, 12, and 26 weeks)
measure: Body mass index (kg/m^2)
timeFrame: Changes from baseline. Fasted state at all four visits (Baseline and after 6, 12, and 26 weeks)
measure: Fat mass (kg)
timeFrame: Changes from baseline. Fasted state at all four visits (Baseline and after 6, 12, and 26 weeks)
measure: Fat free mass (kg)
timeFrame: Changes from baseline. Fasted state at all four visits (Baseline and after 6, 12, and 26 weeks)
measure: Fat percentage (%)
timeFrame: Changes from baseline. Fasted state at all four visits (Baseline and after 6, 12, and 26 weeks)
measure: Waist circumference (cm)
timeFrame: Changes from baseline. Fasted state at all four visits (Baseline and after 6, 12, and 26 weeks)
measure: Hip circumference (cm)
timeFrame: Changes from baseline. Fasted state at all four visits (Baseline and after 6, 12, and 26 weeks)
measure: HbA1c (mmol/mol and %)
timeFrame: Changes from baseline. All four visits (Baseline and after 6, 12, and 26 weeks)
measure: Systolic blood pressure (mmHg)
timeFrame: Changes from baseline. Measured at all four visits (Baseline and after 6, 12, and 26 weeks)
measure: Diastolic blood pressure (mmHg)
timeFrame: Changes from baseline. Measured at all four visits (Baseline and after 6, 12, and 26 weeks)
measure: Heart rate (bpm)
timeFrame: Changes from baseline. Measured at all four visits (Baseline and after 6, 12, and 26 weeks)
measure: Resting energy expenditure (kcal/day)
timeFrame: Changes from baseline. Measured at visits at baseline and after 12 weeks
measure: Substrate oxidation (respiratory exchange ratio)
timeFrame: Changes from baseline. Measured at visits at baseline and after 12 weeks
measure: Metabolites
timeFrame: Changes from baseline. Measured in the blood in the fasted state at all four visits (Baseline and after 6, 12, and 26 weeks) and during a mixed meal test (4 hours) at baseline and end of the intervention (after 12 weeks)
measure: Hormones
timeFrame: Changes from baseline. Measured in the blood in the fasted state at all four visits (Baseline and after 6, 12, and 26 weeks) and during a mixed meal test (4 hours) at baseline and end of the intervention (after 12 weeks)
measure: Circulating proteins that associate with low-grade inflammation and lipid metabolism
timeFrame: Changes from baseline. Fasted state at all four visits (Baseline and after 6, 12, and 26 weeks)
measure: Respiratory and glycolytic capacities of isolated peripheral blood mononuclear cells (PBMCs)
timeFrame: Changes from baseline. Fasted state at all four visits (Baseline and after 6, 12, and 26 weeks) and during a mixed meal test at baseline and end of the intervention (after 12 weeks)
measure: Heart rate response to standing up from the supine position
timeFrame: Changes from baseline. Measured at visits at baseline and end of the intervention (after 12 weeks)
measure: Heart rate response to inhalation and exhalation
timeFrame: Changes from baseline. Measured at visits at baseline and end of the intervention (after 12 weeks)
measure: Heart rate response to forced exhalation during rest (valsalva maneuver)
timeFrame: Changes from baseline. Measured at visits at baseline and end of the intervention (after 12 weeks)
measure: Gastric emptying time (hours and minutes)
timeFrame: Changes from baseline. Time after consumption of the standard mixed meal at baseline and end of the intervention (after 12 weeks).
measure: Small bowel transit time (hours and minutes)
timeFrame: Changes from baseline. Time after consumption of the standard mixed meal at baseline and end of the intervention (after 12 weeks).
measure: Large bowel transit time (hours and minutes)
timeFrame: Changes from baseline. Time after consumption of the standard mixed meal at baseline and end of the intervention (after 12 weeks).
measure: Total gastrointestinal transit time (hours and minutes)
timeFrame: Changes from baseline. Time after consumption of the standard mixed meal at baseline and end of the intervention (after 12 weeks).
measure: Motility index
timeFrame: Changes from baseline. Time after consumption of the standard mixed meal at baseline and end of the intervention (after 12 weeks).
measure: Attention measured using eye tracking
timeFrame: Changes from baseline. Fasted state at all four visits (Baseline and after 6, 12, and 26 weeks) and during a mixed meal test at baseline and end of the intervention (after 12 weeks)
measure: Emotions measured using facial expression analyses
timeFrame: Changes from baseline. Fasted state at all four visits (baseline and after 6, 12, and 26 weeks) and during a mixed meal test at baseline and end of the intervention (after 12 weeks)
measure: Arousal measured using galvanic skin response
timeFrame: Changes from baseline. Fasted state at all four visits (Baseline and after 6, 12, and 26 weeks) and during a mixed meal test at baseline and end of the intervention (after 12 weeks)
measure: Food choice
timeFrame: Changes from baseline. Fasted state at all four visits (Baseline and after 6, 12, and 26 weeks) and during a mixed meal test at baseline and end of the intervention (after 12 weeks)
measure: Implicit wanting
timeFrame: Changes from baseline. Fasted state at all four visits (Baseline and after 6, 12, and 26 weeks) and during a mixed meal test at baseline and end of the intervention (after 12 weeks)
measure: Explicit liking
timeFrame: Changes from baseline. Fasted state at all four visits (Baseline and after 6, 12, and 26 weeks) and during a mixed meal test at baseline and end of the intervention (after 12 weeks)
measure: Explicit wanting
timeFrame: Changes from baseline. Fasted state at all four visits (Baseline and after 6, 12, and 26 weeks) and during a mixed meal test at baseline and end of the intervention (after 12 weeks)
measure: Insulin sensitivity (indices)
timeFrame: At all four visits (Baseline and after 6, 12, and 26 weeks)
measure: Insulin resistance (indices)
timeFrame: At all four visits (Baseline and after 6, 12, and 26 weeks)
measure: Subjective appetite
timeFrame: Changes from baseline. Fasted state at all four visits (Baseline and after 6, 12, and 26 weeks) and during a mixed meal test at baseline and end of the intervention (after 12 weeks)
measure: Mean amplitude of glycaemic excursions (MAGE)
timeFrame: Changes from baseline. Measured 7 days after the test days at baseline and after 6 and 12 weeks
measure: Continuous overall net glycaemic action (CONGA)
timeFrame: Changes from baseline. Measured 7 days after the test days at baseline and after 6 and 12 weeks
measure: Daily time spent above different glucose concentrations (e.g. >6.1 mmol/L, >7.0 mmol/L, >7.8 mmol/L, and >11.1 mmol/L)
timeFrame: Changes from baseline. Measured 7 days after the test days at baseline and after 6 and 12 weeks
measure: Mean glucose concentrations
timeFrame: Changes from baseline. Measured 7 days after the test days at baseline and after 6 and 12 weeks
measure: Standard deviation of glucose concentrations
timeFrame: Changes from baseline. Measured 7 days after the test days at baseline and after 6 and 12 weeks
measure: Variation coefficients of glucose concentrations
timeFrame: Changes from baseline. Measured 7 days after the test days at baseline and after 6 and 12 weeks
measure: Physical activity (time spent at different intensities)
timeFrame: Changes from baseline. Measured 7 days after the test days at baseline and after 6 and 12 weeks
measure: Physical activity (counts/min)
timeFrame: Changes from baseline. Measured 7 days after the test days at baseline and after 6 and 12 weeks
measure: Physical activity energy expenditure (kcal/day)
timeFrame: Changes from baseline. Measured 7 days after the test days at baseline and after 6 and 12 weeks
measure: Physical activity (MET hours)
timeFrame: Changes from baseline. Measured 7 days after the test days at baseline and after 6 and 12 weeks
measure: Timing of physical activity (hh:mm)
timeFrame: Changes from baseline. Measured 7 days after the test days at baseline and after 6 and 12 weeks
measure: Energy intake (kcal/day)
timeFrame: Changes from baseline. Registered 3 days after the test days at baseline and after 6 and 12 weeks
measure: Macronutrient intake (energy percentage)
timeFrame: Changes from baseline. Registered 3 days after the test days at baseline and after 6 and 12 weeks
measure: Timing of dietary intake (hh:mm)
timeFrame: Changes from baseline. Registered 3 days after the test days at baseline and after 6 and 12 weeks
measure: Sleep timing (hh:mm)
timeFrame: Changes from baseline. Registered and measured for 7 days after the test days at baseline and after 6 and 12 weeks
measure: Sleep duration (min)
timeFrame: Changes from baseline. Registered and measured for 7 days after the test days at baseline and after 6 and 12 weeks
measure: Sleep variability (min)
timeFrame: Changes from baseline. Registered and measured for 7 days after the test days at baseline and after 6 and 12 weeks
measure: Sleep onset latency (min)
timeFrame: Changes from baseline. Registered and measured for 7 days after the test days at baseline and after 6 and 12 weeks
measure: Sleep efficiency (%)
timeFrame: Changes from baseline. Measured for 7 days after the test days at baseline and after 6 and 12 weeks
measure: Wakefulness (min)
timeFrame: Changes from baseline. Measured for 7 days after the test days at baseline and after 6 and 12 weeks
measure: Self-reported gastrointestinal symptoms (part 1)
timeFrame: Changes from baseline. Assessed at all four visits (Baseline and after 6, 12, and 26 weeks)
measure: Self-reported gastrointestinal symptoms (part 2)
timeFrame: Changes from baseline. Assessed at all four visits (Baseline and after 6, 12, and 26 weeks)
measure: Self-reported gastrointestinal symptoms (part 3)
timeFrame: Changes from baseline. Registered 7 days after the test days at baseline and after 12 weeks
measure: Self-reported autonomic symptoms
timeFrame: Changes from baseline. Assessed at all four visits (Baseline and after 6, 12, and 26 weeks)
measure: Self-reported control over eating
timeFrame: Changes from baseline. Assessed at all four visits (Baseline and after 6, 12, and 26 weeks)
measure: Self-reported sleepiness
timeFrame: Changes from baseline. Assessed at all four visits (Baseline and after 6, 12, and 26 weeks)
measure: Self-reported sleep quality
timeFrame: Changes from baseline. Assessed at all four visits (Baseline and after 6, 12, and 26 weeks)
measure: Self-reported chronotype
timeFrame: Changes from baseline. Assessed at all four visits (Baseline and after 6, 12, and 26 weeks)
measure: Self-reported physical activity
timeFrame: Changes from baseline. Assessed at all four visits (Baseline and after 6, 12, and 26 weeks)
measure: Self-reported overall health and wellbeing
timeFrame: Changes from baseline. Assessed at all four visits (Baseline and after 6, 12, and 26 weeks)
measure: Self-reported eating behavior
timeFrame: Changes from baseline. Assessed at all four visits (Baseline and after 6, 12, and 26 weeks)
measure: Self-reported night eating
timeFrame: Changes from baseline. Assessed at all four visits (Baseline and after 6, 12, and 26 weeks)
measure: Daily eating/drinking window (hh:min)
timeFrame: Registrered every day (13 weeks intervention and 13 weeks follow-up period)
measure: Microbiome content and diversity
timeFrame: Changes from baseline. Collected before or during test days at visits at baseline and after 12 weeks
measure: Motivation for participation (qualitative methods)
timeFrame: Visits at baseline and after 12 and 26 weeks. Potential drop-outs will be interviewed at the specific time point.
measure: Feasibility of the intervention (qualitative methods)
timeFrame: Visits at baseline and after 12 and 26 weeks. Potential drop-outs will be interviewed at the specific time point.
measure: Satisfaction with the intervention (qualitative methods)
timeFrame: Visits at baseline and after 12 and 26 weeks. Potential drop-outs will be interviewed at the specific time point.
Other outcomes:
Locations:
city: Gentofte
country: Denmark
facility: Steno Diabetes Center Copenhagen
Study officials:
affiliation: Steno Diabetes Center Copenhagen
name: Kristine Færch, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Quist JS, Jensen MM, Clemmensen KKB, Pedersen H, Bjerre N, Storling J, Blond MB, Wewer Albrechtsen NJ, Holst JJ, Torekov SS, Vistisen D, Jorgensen ME, Panda S, Brock C, Finlayson G, Faerch K. Protocol for a single-centre, parallel-group, randomised, controlled, superiority trial on the effects of time-restricted eating on body weight, behaviour and metabolism in individuals at high risk of type 2 diabetes: the REStricted Eating Time (RESET) study. BMJ Open. 2020 Aug 26;10(8):e037166. doi: 10.1136/bmjopen-2020-037166.