Time RestrIcted Feeding For Improving Diabetes Risk (TRIFFID) (TRIFFID)

• ClinicalTrials.gov Identifier: NCT03590158
• Recruitment Status: Completed
• First Posted: July 18, 2018
• Last Update Posted: July 30, 2019
• Sponsor: University of Adelaide
• Collaborators: University of South Australia; Salk Institute for Biological Studies
• Information provided by (Responsible Party): A/Prof Leonie Heilbronn, University of Adelaide

Study Description

Brief Summary:

This study will explore the effects of eight weeks of time-restricted feeding (TRF) on body weight and composition, glycaemic control, 24-hour glucose profiles, glucoregulatory hormones, and cardiovascular risk in men at high risk of type 2 diabetes. The investigators hypothesise that 8 weeks of TRF will reduce body weight, improve body composition, improve glycaemic control and blood lipid profiles. The potential mechanism will be explored in terms of the changes in gene expression patterns and multi-omics level (e.g., adipose tissue transcriptome, blood proteome).

Condition or disease	Intervention/treatment	Phase
Type2 Diabetes; Obesity	Behavioral: TRF	Not Applicable

Detailed Description:

Following a 2 week baseline monitoring phase (food intake by smartphone APP, activity by accelerometer, glucose by continuous glucose monitor), participants will attend the metabolic clinic for testing (visit 0). Body weight, body composition (by DEXA), and blood pressure will be assessed. Blood and adipose tissue samples will be collected over 24-hour period for assessment of glucose, insulin, glucoregulatory hormones, blood lipids and adipose tissue transcriptome. Glucose and insulin responses to a standardised breakfast will be measured. All food will be provided for 3 days prior to the metabolic visit. Following visit 0, participants will be instructed to eat only within a 10-hour time frame each day for 8 weeks. Participants may self-select the precise window that best suits their lifestyles, however any food and drink must be consumed at least 3 hours prior to their usual bedtime. 24-hour glucose profiles, activity and food intake will be measured again at week 6-8. At the end of the 8 weeks, participants will return for a follow-up metabolic visit, identical to that at visit 0, except foods are provided with the 10h time frame.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: The Metabolic Impacts of Time-restricted Feeding in Men at High Risk of Type 2 Diabetes
• Actual Study Start Date: July 17, 2018
• Actual Primary Completion Date: June 29, 2019
• Actual Study Completion Date: June 29, 2019

Arms and Interventions

Arm

Intervention/treatment

Experimental: TRF; Participants will follow their regular diet for two weeks before 3-day lead-in food prior to the metabolic testing at visit 0. Participants will then be instructed to eat their habitual diet only within a 10-hour time frame each day for 8 weeks. Participants may self-select the precise window that best suits their lifestyles, however any food and drink must be consumed by 7:30pm.

Behavioral: TRF; Participants will be instructed to consume their habitual diet within a self-selected 10 hour period every day.

Outcome Measures

Primary Outcome Measures :

1. Glycaemia [ Time Frame: 2.5 hours ]
   Change in postprandial glucose (iAUC) following a standard breakfast

Secondary Outcome Measures :

1. Insulin [ Time Frame: 2.5 hours ]
   Change in fasting and postprandial insulin following a standard breakfast.
2. HbA1c [ Time Frame: 8 weeks ]
   Change in HbA1c
3. Body weight [ Time Frame: 8 weeks ]
   Change in body weight
4. Body composition [ Time Frame: 8 weeks ]
   Change in body fat mass and fat free mass
5. Waist and hip circumference [ Time Frame: 8 weeks ]
   Change in waist and hip circumference
6. 24-hour glucose profile [ Time Frame: 8 weeks ]
   Change in 24-hour glucose profiles assessed by continuous glucose monitoring
7. Blood pressure [ Time Frame: 8 weeks ]
   Changes in systolic blood pressure and diastolic blood pressure
8. Blood lipids [ Time Frame: 8 weeks ]
   changes in blood lipid profile (total cholesterol, HDL-, LDL- cholesterol and triglycerides)
9. Non-esterified fatty acid (NEFA) [ Time Frame: 8 weeks ]
   Change in non-essential fatty acid (NEFA)
10. Plasma gastrointestinal (GI) hormones [ Time Frame: 8 weeks ]
    Changes in concentration of fasting and postprandial GI hormones in plasma (ghrelin, glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, peptide YY) following a standard breakfast.
11. Plasma cortisol [ Time Frame: 8 weeks ]
    Changes in concentration of cortisol in hourly plasma samples assessed from 6am to 12pm.
12. Plasma Melatonin [ Time Frame: 8 weeks ]
    Changes in dim light melatonin onset (DLMO) assessed from 5pm to 3am
13. Adipose tissue transcriptome [ Time Frame: 8 weeks ]
    A subset will be measured for the change in the adipose tissue transcriptome in 6-hourly samples by RNA-sequencing. The data analysis including but not limited to the changes in numbers of genes oscillated in a diurnal manner, and pathway analysis.
14. Evening glycaemia [ Time Frame: 8 weeks ]
    An ancillary study will be performed to measure the changes in the concentration of plasma glucose, insulin and GI hormones (ghrelin, glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, peptide YY) following a standard evening meal.
15. Physical activity and sleep [ Time Frame: 8 weeks ]
    An ancillary study will measure the changes in sleep and physical activity monitored by a wrist actigraph for 14 days.
16. Food intake and meal timing [ Time Frame: 8 weeks ]
    An ancillary study will measure the changes in food intake and meal timing as recorded via a photography based smartphone App over 2 weeks. The analysis of the App data including but not limited to eating duration at baseline, changes in eating duration after intervention, calorie distribution throughout the day, meal frequency, meal intervals, and macronutrients intake.
17. Continuous glucose monitoring [ Time Frame: 8 weeks ]
    An ancillary study will measure the changes in glucose level by CGM for 14 days. Daily glucose patterns including free habitual diet, 3-day lead-in food will be measured separately. The analysis of the CGM data including but not limited to assess the mean amplitude of glycaemic excursions (MAGE), continuous overall net glycaemic action (CONGA), mean glucose concentrations.
18. Objective sleep [ Time Frame: 8 weeks ]
    Changes in objective sleep status measured by laboratory polysomnography (PSG).

Other Outcome Measures:

1. Hair follicle clock gene expression [ Time Frame: 8 weeks ]
   Changes in the circadian pattern of clock gene expression in hair follicles.
2. Resting metabolic rate [ Time Frame: 8 weeks ]
   A subset of participants will be examined for the changes in resting metabolic rate and respiratory quotient.
3. Metagenomics and metabolomics [ Time Frame: 8 weeks ]
   Changes in metagenome and metabolome in a subset of participants will be assessed in faeces by shotgun metagenomics sequencing and metabolites analysis. The data analysis including but not limited to the function and composition of the gut microbiota, and faecal bile acids.
4. Plasma proteome [ Time Frame: 8 weeks ]
   Plasma proteome will be assessed by mass-spectrometry driven analysis. The data analysis including but not limited to the changes in numbers of proteins oscillated in a diurnal manner, and pathway analysis.

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Waist circumference ≥94 cm
• Weight-stable (< 5 % fluctuation in their body weight for past 6-months at study entry)

Exclusion Criteria:

• Personal history and/or diagnosis of: diabetes, cancer, major psychiatric disorders, liver disease, gastro-intestinal surgery or disease (including malabsorption), eating disorders, anaemia, insomnia, cardiovascular disease deemed unstable by the study physician.
• use of prescribed or non-prescribed medications which may affect energy metabolism, gastrointestinal function, body weight or appetite, sleep (e.g: domperidone and cisapride, anticholinergic drugs (e.g.: atropine), metoclopramide, orlistat, thyroid medications, diuretics, glucocorticoids, sex steroids, metformin, dipeptidyl peptidase-IV inhibitors, melatonin)
• recent weight change in past 3 months (> 5% current body weight)
• individuals who regularly perform high intensity exercise (>2 week)
• current intake of > 140g alcohol/week
• current smokers of cigarettes/cigars/marijuana/e-cigarettes/vaporisers
• current intake of any illicit substance
• unable to comprehend study protocol
• currently performing shift work
• has undertaken, or is planning to undertake, trans meridian travel during the study period, or the preceding 60 days
• do not own a smartphone
• eats for less than a 12-hour period per day

Contacts and Locations

Locations

Australia, South Australia

University of Adelaide

Adelaide, South Australia, Australia

Sponsors and Collaborators

University of Adelaide

University of South Australia

Salk Institute for Biological Studies

Investigators

• Principal Investigator: Leonie Heilbronn, PhD; University of Adelaide

More Information

• Responsible Party: A/Prof Leonie Heilbronn, A/Prof, University of Adelaide
• ClinicalTrials.gov Identifier: NCT03590158
• Other Study ID Numbers: R20180320
• First Posted: July 18, 2018
• Last Update Posted: July 30, 2019
• Last Verified: July 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases