High FODMAP Diet With Metformin in preDM

Study Overview
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Brief Summary
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This is a prospective, double blinded, randomised cross over feeding trial examine high or low FODMAP diet in combination with metformin on postprandial glucose responses and gastrointestinal tolerability and gut microbiota profiles. The trial will compare high or low FODMAP diet, each of 10 days duration in combination with 5 days metformin, separated by a washout period of at least 2 weeks.

Official Title
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The Impact of High or Low FODMAP Diets on Postprandial Glucose Response and Gut Microbiota in Individuals With Prediabetes Treated With Metformin: A Randomized Crossover Controlled-Feeding Trial

Conditions
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PreDiabetes, Impaired Glucose Tolerance

Intervention / Treatment
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* Combination Product: High FODMAP diet with metformin
* Combination Product: Low FODMAP diet with metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-70 years Body mass index 18 to 40 kg/m 2 Prediabetes defined as impaired fasting PG 5.6-6.9 mmol/l and/or impaired glucose tolerance with 2-hour PG 7.8-11.1 mmol/l on 75g oral glucose tolerance test (OGTT) and/or HbA1c 5.7-6.4% at screening Exclusion Criteria: Currently pregnant, lactating, as demonstrated by a positive pregnancy test at screening or planning pregnancy Known current diabetes Current or previous use of glucose-lowering or weight loss drugs in 3 months prior to screening Concurrent participation in other weight loss or lifestyle intervention programmes Current use or recent exposure to any medication that in the opinion of the investigator could have an influence on the patient's ability to participate in this study or on the performance of the test device. Recent intake of prebiotic/probiotic or antibiotic, immunosuppressants (within 8 weeks of randomisation) Extensive skin changes/diseases that preclude wearing the FGM on normal skin at the proposed application sites (e.g., extensive psoriasis, recent burns or severe sunburn, extensive eczema, extensive scarring, extensive tattoos, dermatitis herpetiformis). Known uncontrolled thyrotoxicosis Known vitamin B deficiency Known irritable bowel syndrome or gastrointestinal disorders Estimated glomerular filtration rate (eGFR) <45 ml/min/1.73m2 at screening Current use of steroids Have a known allergy to medical-grade adhesives Known current or recent alcohol or drug abuse Hypersensitivity to metformin Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma within 3 months of randomisation Currently participating in another investigational study protocol where the testing or results may interfere with study compliance, diagnostic results, or data collection. An identified protected vulnerable patient (including but not limited to those in detention, or a prisoner). Participants who are on a vegetarian or vegan diet as their habitual diet at screening. Participants with clinically significant food allergy to components of the study diet

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High FODMAP<br> | Combination Product: High FODMAP diet with metformin<br>* Controlled High FODMAP diet (15g/day) from day 1-10, metformin XR 1000mg daily day 6-10 for each treatment period<br>|
| Placebo Comparator: LOW FODMAP<br> | Combination Product: Low FODMAP diet with metformin<br>* Controlled low FODMAP diet (3g/day) from day 1-10, metformin XR 1000mg daily day 6-10 for each treatment period<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in postprandial glycemia | incremental area under curve on continuous glucose monitoring post meal | 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose response to 75g oral glucose tolerance test | fasting and postchallenge plasma glucose | 10 days | 
| Insulin response to 75g oral glucose tolerance test | insulin levels | 10 days | 
| Change in alpha diversity of gut microbiota | Changes in alpha diversity in gut microbiota | 10 days | 
| Change in beta diversity of gut microbiota | Changes in beta diversity in gut microbiota | 10 days | 
| Body weight | Differences in body weight between arms | 10 days | 
| Gastrointestinal symptoms | Measured on visual analogue scale 1-10 for each item, higher score indicates worse symptoms | 10 days |