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Trial registered on ANZCTR


Registration number
ACTRN12616001050448
Ethics application status
Approved
Date submitted
16/07/2016
Date registered
5/08/2016
Date last updated
23/09/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy of probiotics and/or intermittent fasting to improve prediabetes
Scientific title
PRObiotics and intermittent FASTing to improve prediabetes (PROFAST) study
Secondary ID [1] 289674 0
Nil known
Universal Trial Number (UTN)
U1111-1185-3564
Trial acronym
PROFAST
Linked study record

Health condition
Health condition(s) or problem(s) studied:
prediabetes 299473 0
type 2 diabetes 299474 0
Condition category
Condition code
Diet and Nutrition 299452 299452 0 0
Obesity
Metabolic and Endocrine 299453 299453 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
1. Daily probiotic capsule (containing Lactobacillus rhamnosus HN001, at a dose of 6x10^9cfu) for 1 year plus usual healthy diet (according to standard dietary guidelines) for 1 year
2. Daily probiotic capsule (containing Lactobacillus rhamnosus HN001, at a dose of 6x10^9cfu) for 1 year plus intermittent fasting (2 out of 7 days) when 600kcal/day is consumed by women and 650kcal/day is consumed by men, for 1 year
3. Daily placebo capsule (containing corn-derived maltodextrin with identical appearance and similar smell to the probiotic capsule) for 1 year plus intermittent fasting (2 out of 7 days) when 600kcal/day is consumed by women and 650kcal/day is consumed by men, for 1 year
4. Placebo capsule (containing corn-derived maltodextrin with identical appearance and similar smell to the probiotic capsule) for 1 year plus usual healthy diet (according to standard dietary guidelines) for 1 year

Strategies to monitor adherence with daily capsules will be empty capsule packet return and self-reported adherence.
Strategies to monitor adherence with diet will be food diary and reported adherence
Guidance on intermittent fasting will include 4 x 1 hour duration group/individual sessions with a dietitian for tailored IF advice (at baseline, 2, 4 and 8 weeks), and resource list with written material, choice of apps, books and invited, closed social networking site for intermittent fasting study group members moderated by a dietitian. Participants will self-select individual or group sessions. The intermittent fasting days will be selected by the participants as either consecutive or non-consecutive days. No specific instruction for the 5 non-fasting days will be given other than usual healthy diet pamphlet and recommendations regarding physical activity will be provided to both dietary groups.
Guidance on usual health diet will include only a usual health diet pamphlet. No specific contact with a dietitian or additional resources will be provided.
Intervention code [1] 295294 0
Prevention
Intervention code [2] 295295 0
Treatment: Other
Comparator / control treatment
Placebo capsule (containing corn-derived maltodextrin with identical appearance and similar smell to the probiotic capsule)
Routine dietary advice (as per NZ Ministry of Health Eating and Activity Guidelines) and pamphlet (diabetes prevention brochure by Auckland DHB & Diabetes Projects Trust, available on www.pt.org.nz/upload/pdfs/ENG_diabetes_prevent.pdf)
Control group
Placebo

Outcomes
Primary outcome [1] 298937 0
Change in HbA1c from baseline
Timepoint [1] 298937 0
3 months and 1 year
Secondary outcome [1] 325683 0
Change in weight (measured by digital scales)
Timepoint [1] 325683 0
at 3 months and at 1 year
Secondary outcome [2] 325684 0
Change in well being scores using SF12
Timepoint [2] 325684 0
3 months and 1 year
Secondary outcome [3] 325685 0
metabolic syndrome components (blood pressure measured by sphygmomanometry, lipids measured by Roche Diagnosticc cobas analyser) from baseline
Timepoint [3] 325685 0
at 3 months and at 1 year
Secondary outcome [4] 325686 0
composite secondary outcome of any change in liver and pancreatic fat content on MRI/MRS
Timepoint [4] 325686 0
at 3 months and at 1 year
Secondary outcome [5] 325687 0
Composite secondary outcome of change in gut hormones and inflammatory markers (active GLP-1, total GIP, active ghrelin, glucagon, pancreatic polypeptide, leptin, Il-6, MCP-1, TNF-alpha, using Luminex magnetic bead technology of plasma samples)
Timepoint [5] 325687 0
at 3 months and 1 year
Secondary outcome [6] 325688 0
Composite secondary outcome of alteration in insulin sensitivity and OGTT derived measures of beta cell function
Insulin sensitivity is assessed using HOMA-S
OGTT derived measures of beta cell function uses insulinogenic index (insulin[30min]-insulin[0min])/([glucose[30min]-glucose[0min], and disposition index as product of 1/(fasting insulin x IGI)
Timepoint [6] 325688 0
at 3 months and at 1 year

Eligibility
Key inclusion criteria
Prediabetes defined by HbA1c 41-49 mmol/mol inclusive
BMI of 30-40 (or 27-40 if Asian Indian ethnicity)
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Previous bariatric surgery, BMI >40kg/m2, on glucose lowering medications, conditions that might influence body weight regulation (eg: malabsorption, thyroid disorders, eating disorders, use of systemic steroids, excess alcohol intake (>21 units per week in men, >14 units per week in women), stable body weight in previous 6 months, planned major changes in physical activity during the study to an extent that might interfere with the study outcome, blood donation withthin past 2 months prior to the study (and at the endpoints), adults with a weight change of >3kg within 3 months prior to first baseline visit, psychiatric disease, pregnant women or lactating, or intending to become pregnant within the study duration, significant renal disease (GFR<30), congestive heart failure, unexplained syncope, recent myocardial infarction or stroke within 6 months, porphyria, thalassemia (or other blood disorders in which HbA1c is inaccurate for glycemia), splenectomy, participation in other clinical studies within the previous 6 months, not accepting of 5:2 intermittent fasting or probiotic supplementation. For the MRI studies, those with any implanted metal or electornic devices will not be able to take part.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
allocation concealment will be ensured by central randomisation schedule by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
web-based protocol, with random number codes
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
To allow for 10% loss to follow up, we will recruit 560 participants with prediabetes. A total sample size of 504 people with prediabetes (126 per arm), provides 90% power to detect a minimum effect size of 2.5mmol/mol difference in HbA1c in one of the 3 intervention strategies: arms (1), (2) or (3), relative to control arm (4), using the Dunnett (with control) multiple comparison test at a 5% significance level (PASS 13, version 13.0.4). The standard deviation for change in HbA1c is assumed to be 4mmol/mol as reported in other prediabetes nutritional intervention studies. The effect size of 2.5mmol/mol has been chosen to be the minimum clinically significant reduction in HbA1c among patients selected to have prediabetes. This sample size will also have 90% power to detect an interaction effect of 2.3mmol/mol between intermittent fasting and probiotic.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 8031 0
New Zealand
State/province [1] 8031 0
Auckland

Funding & Sponsors
Funding source category [1] 294073 0
Government body
Name [1] 294073 0
Health Research Council
Address [1] 294073 0
HRC, Level 3, 110 Stanley St, Grafton, Auckland 1010, NZ
Country [1] 294073 0
New Zealand
Primary sponsor type
University
Name
University of Auckland
Address
The University of Auckland
Private Bag 92019
Auckland 1142, New Zealand
Country
New Zealand
Secondary sponsor category [1] 292904 0
None
Name [1] 292904 0
Address [1] 292904 0
Country [1] 292904 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295487 0
Health and Disability Ethics Committee
Ethics committee address [1] 295487 0
Ministry of Health
Ethics Department
Freyberg Building
Reception – Ground Floor
20 Aitken Street
Wellington 6011
Ethics committee country [1] 295487 0
New Zealand
Date submitted for ethics approval [1] 295487 0
18/07/2016
Approval date [1] 295487 0
12/08/2016
Ethics approval number [1] 295487 0

Summary
Brief summary
Preventing the progression from prediabetes to Type 2 Diabetes (T2D) is a health priority for New Zealand. We wish to test the effectiveness of two promising, simple interventions on reducing progression of prediabetes: a daily probiotic supplement and intermittent fasting.

Lactobacillus rhamnosus HN001 probiotic (6x109 cfu dose) has been shown to reduce the incidence of gestational diabetes, so may also prevent progression of prediabetes. The benefits of daily caloric restriction on reducing the risk of T2D are well-known, but this strategy is difficult to sustain. There is some evidence that the benefits of intermittent fasting may be similar, but with greater adherence and acceptability than continuous caloric restriction. Given both of these approaches target the gut microbiota, there is a possibility of synergistic effects through altered pancreatic and liver fat deposition.

The aim of the overall project is to determine whether daily supplementation with a capsule containing L. rhamnosus HN001 or intermittent 5:2 fasting or the combination will reduce progression of prediabetes.

We are proposing a one-year, clinical trial among 560 people with prediabetes who will be randomised to either (1) intermittent fasting (reducing calories to 600kcal/day for women and 650kcal/day for men, on 2 days of every week) + daily probiotic capsule (2) intermittent fasting + daily placebo (3) daily healthy eating efforts + daily probiotic (4) daily healthy eating efforts + daily placebo (control). The primary outcome of this study is HbA1c at 1 year. Key secondary outcomes include change in body weight, body composition (fat partitioning), fasting glucose and fats.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 67406 0
Dr Rinki Murphy
Address 67406 0
Department of Medicine
Faculty of Medical and Health Sciences
The University of Auckland
Private Bage 92019
Auckland 1142
New Zealand
Country 67406 0
New Zealand
Phone 67406 0
+649,9,9236313
Fax 67406 0
Email 67406 0
R.Murphy@auckland.ac.nz
Contact person for public queries
Name 67407 0
Dr Rinki Murphy
Address 67407 0
Department of Medicine
Faculty of Medical and Health Sciences
The University of Auckland
Private Bage 92019
Auckland 1142
New Zealand
Country 67407 0
New Zealand
Phone 67407 0
+649,9,9236313
Fax 67407 0
Email 67407 0
R.Murphy@auckland.ac.nz
Contact person for scientific queries
Name 67408 0
Dr Rinki Murphy
Address 67408 0
Department of Medicine
Faculty of Medical and Health Sciences
The University of Auckland
Private Bage 92019
Auckland 1142
New Zealand
Country 67408 0
New Zealand
Phone 67408 0
+649,9,9236313
Fax 67408 0
Email 67408 0
R.Murphy@auckland.ac.nz

No information has been provided regarding IPD availability
Summary results
No Results