Daily vs Intermittent Restriction of Energy: Controlled Trial to Reduce Diabetes Risk (DIRECT)

NCT03689608 | Completed DMC

• 1 other identifier: R20180319
• Study Type: interventional
• Target: 209
• Locations: 1 country
• Sites: 1

Brief Summary

In this randomized controlled trial, the investigators will compare the long term effectiveness of intermittent fasting (IF) versus an energy matched moderate calorie restriction (CR) over 18 months, and relative to a non-active intervention standard control (SC) in individuals who are at increased risk of developing type 2 diabetes. All participants will be required to attend the blood tests following a 12-hour overnight fast for the "A" visit at Month 0, 2, 6 (active) and 18 (follow up). Fast424hGlucose: A subset of 100 participants enrolled in either IF or CR group in the parent study will be fitted with a continuous glucose monitor (CGM) to measure 24-hour glycaemic profile at month 0 and month 6. Fast4Switch: Additional bloods will be collected after a "B" visit at month 6 to compare the fed to fasted switch. The B samples will be collected after a 12-hour overnight fast (CR, SC) or 20-hour fast (IF) to assess the metabolic switch to fasting in metabolites and hormones. Fast4Stress: Additional subcutaneous adipose tissue, urine and saliva samples will be collected in \~32 men in IF and CR groups at month 0 and 6 at A and B visits to examine changes in stress response and resistance markers. Experience2Fast: In-depth, semi-structured interviews will be carried out at month-8 follow-up visit in a subset of completers from IF or CR groups to explore the experience of intervention diets and understand contributing factors towards change and maintenance of dietary behaviours. Fast4Flux: Additional blood samples will be collected in \~100 individuals in SC, IF and CR groups at month 0, month 2 and month 6 at A visit to measure autophagic flux in peripheral blood mononuclear cells following treatment of whole blood.

Conditions

Individuals at Risk of Developing Diabetes

Keywords

intermittent fasting; calorie restriction; overweight and obesity

Outcome Measures

Primary Outcomes (1)

• Postprandial glucose AUC

  Change in postprandial glucose AUC

  6 months

Secondary Outcomes (16)

• HbA1c

  2 months, 6 months, 18 months

• Postprandial glucose

  18 months

• Body weight

  2 months, 6 months, 18 months

• Body composition

  6 months, 18 months

• Waist and hip circumference

  2 months, 6 months, 18 months

Other Outcomes (26)

• Change in perceived hunger and fullness assessed by visual analogue scales (VAS)

  6 months, 18 months

• Change in perceived sleep quality

  2 months, 6 months, 18 months

• Change in perceived eating behaviour

  2 months, 6 months, 18 months

Study Arms (3)

Intermittent Fasting (IF)

EXPERIMENTAL

3 days fasting per week

Other: Intermittent Fasting (IF)

Daily Restriction (DR)

EXPERIMENTAL

daily energy restriction

Other: Daily Restriction (DR)

standard care (SC)

OTHER

usual care

Other: standard care (SC)

Interventions

Intermittent Fasting (IF) OTHER

Participants will fast 3 days per week. In fasting days, meal replacements at 30% of daily energy requirements will be provided for the first 6 months. Participants will have fortnightly nutrition assessment.

Intermittent Fasting (IF)

Daily Restriction (DR) OTHER

Participants are instructed to restrict energy intake by 30% of daily energy requirements. Meal replacements will be provided for the first 6 months. Participants will have fortnightly nutrition assessment.

Daily Restriction (DR)

standard care (SC) OTHER

Participants will receive current practice guidelines in a static information format, will not take part in any counselling or receive meal replacements.

standard care (SC)

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• weight-stable (\< 5 % fluctuation in their body weight for past 6-months at study entry)
• score 12 or greater on the AUSDRISK calculator
• HbA1c \<48 mmol/mol (measured at screening)

You may not qualify if:

• Personal history/diagnosis (self-reported) of diabetes (type 1 or 2), major psychiatric disorders (schizophrenia, major depressive disorder, bipolar disorder, eating disorders), gastrointestinal disorders, haematological disorders (i.e. thalassemia, iron-deficiency anaemia) insomnia, or any other medical condition, deemed unstable by the study physician.
• Participants currently taking the following medications will be excluded from participating: any medication used to lower blood glucose or antidiabetic medications (metformin, sulfonylureas, Glucagon-like peptide-1 GLP-1 analogues \[i.e. exenatide\], thiazolidinediones or DPP-IV inhibitors \[i.e. 'gliptins'\]), medications affecting weight, appetite or gut motility (i.e. domperidone, cisapride, orlistat, phentermine, topiramate). Participants who are taking stable doses (i.e. \> 12 months) of androgenic medications (i.e. testosterone) or SSRI's will not be excluded.
• weight change in past 3 months (\> 5% screening weight)
• uncontrolled asthma, current fever, upper respiratory infections
• 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 recreational drugs
• regular blood donor
• unable to comprehend study protocol due to English language or cognitive difficulties

Sponsors & Collaborators

• University of Adelaide: lead

Study Sites (1)

University of Adelaide

Adelaide, South Australia, Australia

Location

Related Publications (2)

• Teong XT, Liu K, Vincent AD, Bensalem J, Liu B, Hattersley KJ, Zhao L, Feinle-Bisset C, Sargeant TJ, Wittert GA, Hutchison AT, Heilbronn LK. Intermittent fasting plus early time-restricted eating versus calorie restriction and standard care in adults at risk of type 2 diabetes: a randomized controlled trial. Nat Med. 2023 Apr;29(4):963-972. doi: 10.1038/s41591-023-02287-7. Epub 2023 Apr 6.

  PMID: 37024596 DERIVED

• Teong XT, Liu K, Hutchison AT, Liu B, Feinle-Bisset C, Wittert GA, Lange K, Vincent AD, Heilbronn LK. Rationale and protocol for a randomized controlled trial comparing daily calorie restriction versus intermittent fasting to improve glycaemia in individuals at increased risk of developing type 2 diabetes. Obes Res Clin Pract. 2020 Mar-Apr;14(2):176-183. doi: 10.1016/j.orcp.2020.01.005. Epub 2020 Feb 11.

  PMID: 32057716 DERIVED

MeSH Terms

Conditions

Intermittent Fasting; Overweight; Obesity

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Fasting; Feeding Behavior; Behavior; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Leonie Heilbronn, PhD

  The University of Adelaide

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 26, 2018
• First Posted: September 28, 2018
• Study Start: September 26, 2018
• Primary Completion: November 30, 2020
• Study Completion: November 30, 2021
• Last Updated: January 11, 2022

Record last verified: 2021-12

Locations

AU (1)