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

The Metabolic Impacts of Time-restricted Feeding in Men at High Risk of Type 2 Diabetes

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).

Study Overview

• Status: Completed
• Conditions: Obesity; Type2 Diabetes
• Intervention / Treatment: Behavioral: TRF

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 Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia
      • University of Adelaide

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycaemia	Change in postprandial glucose (iAUC) following a standard breakfast	2.5 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body weight	Change in body weight	8 weeks
Insulin	Change in fasting and postprandial insulin following a standard breakfast.	2.5 hours
HbA1c	Change in HbA1c	8 weeks
Body composition	Change in body fat mass and fat free mass	8 weeks
Waist and hip circumference	Change in waist and hip circumference	8 weeks
24-hour glucose profile	Change in 24-hour glucose profiles assessed by continuous glucose monitoring	8 weeks
Blood pressure	Changes in systolic blood pressure and diastolic blood pressure	8 weeks
Blood lipids	changes in blood lipid profile (total cholesterol, HDL-, LDL- cholesterol and triglycerides)	8 weeks
Non-esterified fatty acid (NEFA)	Change in non-essential fatty acid (NEFA)	8 weeks
Plasma gastrointestinal (GI) hormones	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.	8 weeks
Plasma cortisol	Changes in concentration of cortisol in hourly plasma samples assessed from 6am to 12pm.	8 weeks
Plasma Melatonin	Changes in dim light melatonin onset (DLMO) assessed from 5pm to 3am	8 weeks
Adipose tissue transcriptome	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.	8 weeks
Evening glycaemia	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.	8 weeks
Physical activity and sleep	An ancillary study will measure the changes in sleep and physical activity monitored by a wrist actigraph for 14 days.	8 weeks
Food intake and meal timing	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.	8 weeks
Continuous glucose monitoring	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.	8 weeks
Objective sleep	Changes in objective sleep status measured by laboratory polysomnography (PSG).	8 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hair follicle clock gene expression	Changes in the circadian pattern of clock gene expression in hair follicles.	8 weeks
Resting metabolic rate	A subset of participants will be examined for the changes in resting metabolic rate and respiratory quotient.	8 weeks
Metagenomics and metabolomics	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.	8 weeks
Plasma proteome	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.	8 weeks

Collaborators and Investigators

• Sponsor: University of Adelaide
• Collaborators: Salk Institute for Biological Studies; University of South Australia

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 17, 2018
• Primary Completion (ACTUAL): June 29, 2019
• Study Completion (ACTUAL): June 29, 2019

Study Registration Dates

• First Submitted: July 12, 2018
• First Submitted That Met QC Criteria: July 12, 2018
• First Posted (ACTUAL): July 18, 2018

Study Record Updates

• Last Update Posted (ACTUAL): July 30, 2019
• Last Update Submitted That Met QC Criteria: July 28, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: R20180320

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No