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Completed

NCT Number: NCT03689608

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

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.

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Key information

Conditions

Individuals at Risk of Developing Diabetes Behavior Body Weight Fasting Feeding Behavior Intermittent Fasting Nutrition Disorders Nutritional and Metabolic Diseases Obesity Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

35 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University of Adelaide

Adelaide, South Australia, Australia

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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)

Exclusion criteria

  • 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

Treatment and study plan

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.

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.

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.

Primary outcomes

  1. Postprandial glucose AUC

    Time frame: 6 months

    Change in postprandial glucose AUC

Secondary outcomes

  1. HbA1c

    Time frame: 2 months, 6 months, 18 months

    Change in HbA1c

  2. Postprandial glucose

    Time frame: 18 months

    Change in postprandial glucose

  3. Body weight

    Time frame: 2 months, 6 months, 18 months

    Change in body weight in kilograms

  4. Body composition

    Time frame: 6 months, 18 months

    Change in body fat mass (kg) and fat free mass (kg)

  5. Waist and hip circumference

    Time frame: 2 months, 6 months, 18 months

    Change in waist and hip circumference

  6. Blood lipids

    Time frame: 2 months, 6 months, 18 months

    Changes in blood lipid profile (total cholesterol, HDL-, LDL-cholesterol and triglycerides)

  7. Dietary intake

    Time frame: 2 months, 6 months, 18 months

    Change in food intake measured by self-reported food diaries

  8. Blood pressure

    Time frame: 2 months, 6 months, 18 months

    Change in systolic blood pressure and diastolic blood pressure (mmHg)

  9. Changes in physical Activity assessed by accelerometer

    Time frame: 2 months, 6 months, 18 months

    Change in average step counts measured with waist-worn actigraphy monitors

  10. Fasting glucose

    Time frame: 2 months, 6 months, 18 months

    Change in fasting glucose

  11. Fasting insulin

    Time frame: 2 months, 6 months, 18 months

    Change in fasting insulin

  12. Fasting non-esterified fatty acids (NEFA)

    Time frame: 2 months, 6 months, 18 months

    Change in fasting NEFA levels

  13. Fasting triglyceride

    Time frame: 2 months, 6 months, 18 months

    Change in fasting triglyceride levels

  14. Postprandial insulin

    Time frame: 6 months, 18 months

    Change in postprandial insulin

  15. Postprandial non-esterified fatty acids (NEFA)

    Time frame: 6 months, 18 months

    Change in postprandial NEFA levels

  16. Postprandial triglyceride

    Time frame: 6 months, 18 months

    Change in postprandial triglyceride levels

Other outcomes

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

    Time frame: 6 months, 18 months

    Change in subjective hunger and fullness ratings measured by 0-100 mm VAS scales

  2. Change in perceived sleep quality

    Time frame: 2 months, 6 months, 18 months

    Change in perceived sleep quality assessed by Pittsburgh Sleep Quality Index (PSQI), with a range from 0-21 scores, higher score reflect poorer sleep quality

  3. Change in perceived eating behaviour

    Time frame: 2 months, 6 months, 18 months

    Change in perceived eating behaviour assessed by Three Factor Eating Questionnaire (TFEQ), which consists of 51 items to assess dietary restraint (21 items), disinhibition (16 items) and hunger (14 items), higher scores reflect higher levels on each subscale

  4. Change in perceived quality of life

    Time frame: 2 months, 6 months, 18 months

    Change in perceived quality of life assessed by 36-item Short Form (SF-36) health survey, with a range from 0-100 scores, higher scores reflect better quality of life

  5. Change in perceived well-being

    Time frame: 2 months, 6 months, 18 months

    Change in perceived well-being assessed by Personal Well-being Index, with a range from 0-10 scores, higher scores reflect greater satisfication

  6. Change in food addition score

    Time frame: 6 months, 18 months

    Change in self-reported food addiction assessed by Yale Food Addiction Score (YFAS), with a range from 0-7 scores, higher scores reflect greater food addiction symptoms

  7. Change in psychological distress

    Time frame: 6 months, 18 months

    Change in self-reported psychological distress assessed by Kessler Psychological Distress Scale (K10) , with a range from 10-50 scores, higher scores reflect higher psychological distress

  8. Change in self-reported depression, anxiety and stress level

    Time frame: 2 months, 6 months, 18 months

    Change in self-reported depression, anxiety and stress level assessed by Depression, Anxiety and Stress Scale (DASS), with a range from 0-42 scores on each subscale, higher scores reflect higher levels on each subscale

  9. Change in self-reported mood

    Time frame: 2 months, 6 months, 18 months

    Change in self-reported mood assessed by Positive and Negative Affect Schedule (PANAS), with a range from 0-100 scores, higher scores reflect more positive mood and negative mood.

  10. Change in glucagon-like peptide 1 (GLP-1)

    Time frame: 6 months

    Change in glucagon-like peptide 1 (GLP-1)

  11. Change in peptide YY

    Time frame: 6 months

    Change in peptide YY

  12. Change in ghrelin

    Time frame: 6 months

    Change in ghrelin

  13. Change in gastric inhibitory polypeptide (GIP)

    Time frame: 6 months

    Change in gastric inhibitory polypeptide (GIP)

  14. Change in estradiol

    Time frame: 6 months

    Change in estradiol

  15. Change in testosterone

    Time frame: 6 months

    Change in testosterone

  16. Change in glucose (DIRECT- Fast4Switch)

    Time frame: 6 months

    Change in glucose levels

  17. Change in non-esterified fatty acids (DIRECT- Fast4Switch)

    Time frame: 6 months

    Change in non-esterified fatty acids levels (NEFA)

  18. Change in insulin (DIRECT- Fast4Switch)

    Time frame: 6 months

    Change in insulin levels

  19. Change in triglycerides (DIRECT- Fast4Switch)

    Time frame: 6 months

    Change in triglycerides levels

  20. 24 hours glycaemia (DIRECT-Fast424hGlucose)

    Time frame: 6 months

    Changes in 24 hours glycaemia assessed by continuous glucose monitor

  21. Salivary cortisol (DIRECT-Fast4Stress)

    Time frame: 6 months

    Change in salivary cortisol

  22. Gene expression (DIRECT- Fast4Stress)

    Time frame: 6 months

    Change in gene expression

  23. Change in urinary adrenaline (DIRECT- Fast4Stress)

    Time frame: 6 months

    Change in urinary adrenaline

  24. Change in urinary noradrenaline (DIRECT- Fast4Stress)

    Time frame: 6 months

    Change in urinary noradrenaline

  25. Qualitative analysis (DIRECT-Experience2Fast)

    Time frame: 8 months

    Patterns of participant's behaviour, characteristics and motivation that assist in or hinder from weight loss achievement by semi-structured interviews

  26. Change in autophagic flux (DIRECT-Fast4flux)

    Time frame: 2 months, 6 months

    Change in autophagic machinery protein LC3B-II in peripheral blood mononuclear cells following treatment of whole blood.

Sponsors and collaborators

Lead sponsor

University of Adelaide

Other

Registry information

Official study title

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

Important dates

Study start
2018
Primary completion
2020
Study completion
2021
First posted
Sep 28, 2018
Registry last updated
Jan 11, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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