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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03689608




Registration number
NCT03689608
Ethics application status
Date submitted
26/09/2018
Date registered
28/09/2018
Date last updated
11/01/2022

Titles & IDs
Public title
Daily vs Intermittent Restriction of Energy: Controlled Trial to Reduce Diabetes Risk (DIRECT)
Scientific title
Daily vs Intermittent Restriction of Energy: Randomised Controlled Trial to Reduce Diabetes Risk (DIRECT)
Secondary ID [1] 0 0
R20180319
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Individuals at Risk of Developing Diabetes 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Intermittent Fasting (IF)
Other interventions - Daily Restriction (DR)
Other interventions - standard care (SC)

Experimental: Intermittent Fasting (IF) - 3 days fasting per week

Experimental: Daily Restriction (DR) - daily energy restriction

Other: standard care (SC) - usual care


Other interventions: Intermittent Fasting (IF)
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.

Other interventions: Daily Restriction (DR)
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.

Other interventions: standard care (SC)
Participants will receive current practice guidelines in a static information format, will not take part in any counselling or receive meal replacements.
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Postprandial glucose AUC
Timepoint [1] 0 0
6 months
Secondary outcome [1] 0 0
HbA1c
Timepoint [1] 0 0
2 months, 6 months, 18 months
Secondary outcome [2] 0 0
Postprandial glucose
Timepoint [2] 0 0
18 months
Secondary outcome [3] 0 0
Body weight
Timepoint [3] 0 0
2 months, 6 months, 18 months
Secondary outcome [4] 0 0
Body composition
Timepoint [4] 0 0
6 months, 18 months
Secondary outcome [5] 0 0
Waist and hip circumference
Timepoint [5] 0 0
2 months, 6 months, 18 months
Secondary outcome [6] 0 0
Blood lipids
Timepoint [6] 0 0
2 months, 6 months, 18 months
Secondary outcome [7] 0 0
Dietary intake
Timepoint [7] 0 0
2 months, 6 months, 18 months
Secondary outcome [8] 0 0
Blood pressure
Timepoint [8] 0 0
2 months, 6 months, 18 months
Secondary outcome [9] 0 0
Changes in physical Activity assessed by accelerometer
Timepoint [9] 0 0
2 months, 6 months, 18 months
Secondary outcome [10] 0 0
Fasting glucose
Timepoint [10] 0 0
2 months, 6 months, 18 months
Secondary outcome [11] 0 0
Fasting insulin
Timepoint [11] 0 0
2 months, 6 months, 18 months
Secondary outcome [12] 0 0
Fasting non-esterified fatty acids (NEFA)
Timepoint [12] 0 0
2 months, 6 months, 18 months
Secondary outcome [13] 0 0
Fasting triglyceride
Timepoint [13] 0 0
2 months, 6 months, 18 months
Secondary outcome [14] 0 0
Postprandial insulin
Timepoint [14] 0 0
6 months, 18 months
Secondary outcome [15] 0 0
Postprandial non-esterified fatty acids (NEFA)
Timepoint [15] 0 0
6 months, 18 months
Secondary outcome [16] 0 0
Postprandial triglyceride
Timepoint [16] 0 0
6 months, 18 months

Eligibility
Key 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)
Minimum age
35 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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

Study design
Purpose of the study
Basic Science
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/09/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/11/2021
Sample size
Target
Accrual to date
Final
209
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
University of Adelaide - Adelaide
Recruitment postcode(s) [1] 0 0
- Adelaide

Funding & Sponsors
Primary sponsor type
Other
Name
University of Adelaide
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03689608
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Leonie Heilbronn, PhD
Address 0 0
The University of Adelaide
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03689608