Using a Complex Carbohydrate Mixture to Steer Fermentation and Improve Metabolism in Adults With Overweight and Prediabetes (DISTAL)

Study Overview
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Brief Summary
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The purpose of this study is to investigate the effects of a fibre mixture added to a high-protein diet on metabolic, gut and brain health.

Detailed Description
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The fibre mixture that will be investigated is hypothesized to improved metabolic, gut and brain health. It potentially increases insulin sensitivity, satiety, gut barrier function, improves food-reward related brain activity and decreases inflammation, gut permeability, and ectopic lipid accumulation, among other potential health effects. The fibre mixture will be administrated during 12 weeks combined a high-protein diet. The placebo-controlled parallel design of the study allows for a placebo group to use maltodextrin combined with a high-protein diet for 12 weeks. The high-protein diet is known to increase satiety and might enhance the difference between the intervention and placebo groups in terms of outcome measurements. The potential health effects as described earlier will be investigated using different techniques.

Official Title
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Using a Complex Carbohydrate Mixture Added to a High-protein Diet to Steer Fermentation and Improve Metabolic, Gut and Brain Health

Conditions
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Insulin Resistance, Impaired Glucose Tolerance, PreDiabetes, Overweight and Obesity

Intervention / Treatment
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* Dietary Supplement: Fibre supplement (potato-pectin)
* Dietary Supplement: Placebo
* Dietary Supplement: High-protein diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 30-75 years Male/female BMI 28-40 kg/m2 Impaired fasting glucose or glucose tolerance, determined using the following criteria (participant should meet at least one criteria): HbA1c 42-47 mmol/mol OR fasting glucose (>10h fasted) 5.6-6.9 mmol/l OR Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) >1.85 Exclusion Criteria: Diabetes mellitus (type 1 or 2) Cardiovascular disease (except hypertension (<160/100mmHg is allowed), pulmonary disease, kidney disease/failure, liver disease/failure Gastrointestinal disease or a history of abdominal surgery (except appendectomy and cholecystectomy) Diseases affecting glucose and/or lipid metabolism Malignancy (except non-invasive skin cancer) Auto-immune disease Major mental disorders Ongoing (infectious) disease or any disease with a life expectancy ≤5 years Substance abuse (nicotine abuse (including e-cigarettes) defined as >20 cigarettes per day; alcohol abuse defined as ≥8 drinks/week for females and ≥15 drinks/week for males(38); any drugs) A change in weight ≥3kg over the last 3 months or plans to lose weight or follow a hypocaloric diet during the study period Pre/pro/antibiotic use in the last 3 months or during the study Use of medication that influences glucose or fat metabolism and inflammation, such as: Use of statins (stable use ≥3 months prior to and during study is allowed) Use of antidepressants (stable use ≥3 months prior to and during study is allowed) Use of specific anticoagulants Use of medication known to interfere with study outcomes Use of β-blockers Chronic corticosteroid treatment (>7 consecutive days) Regular use of laxatives 3 months prior to the study or during study period Change in physical activity or diet during study period Intensive physical activity (>3h per week) Pregnancy Following a vegan or vegetarian diet; presence of food allergies, intolerances or diet restrictions interfering with the study.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fibre mixture group<br>Use of a fibre mixture (3 times daily, 5 grams per gift, total of 15 grams per day) during 12 weeks | Dietary Supplement: Fibre supplement (potato-pectin)<br>* Fibre supplement<br>Dietary Supplement: High-protein diet<br>* High-protein diet<br>|
| Placebo Comparator: Placebo group<br>Use of a placebo (maltodextrin, isocaloric manner, 3 times daily) during 12 weeks. | Dietary Supplement: Placebo<br>* Maltodextrin<br>* Other names: Maltodextrin;Dietary Supplement: High-protein diet<br>* High-protein diet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peripheral insulin sensitivity | Change in peripheral insulin sensitivity between the two groups. Measured using a two-step hyperinsulinemic-euglycemic clamp | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin sensitivity (hepatic and adipose tissue) | Change in insulin sensitivity between the two groups. Measured using a two-step hyperinsulinemic-euglycemic clamp | 12 weeks | 
| Gut permeability | Difference in change between the groups. Measured using multisugar test | 12 weeks | 
| Inflammation | Difference in change between the groups. Measured using serum values. | 12 weeks | 
| Energy and substrate metabolism | Difference in change between the groups. Measured using serum values (circulating metabolites) and indirect calorimetry (energy harvest and expenditure) | 12 weeks | 
| Neurocognitive functioning | Difference in change between the groups. Measured using neurocognitive tests and functional Magnetic Resonance Imaging (fMRI). Neurocognitive functioning will be measured using the Cambridge Neuropsychological Test Automated Battery (CANTAB) (a combination of different digital tests) to assess response time in seconds and quality of delivered results. fMRI assesses food-reward related brain activity. | 12 weeks | 
| Food reward related brain activity | Difference in change between the groups. Measured using neurocognitive tests and fMRI. Neurocognitive functioning will be measured using CANTAB (a combination of different digital tests) to assess response time in seconds and quality of delivered results. fMRI assesses food-reward related brain activity | 12 weeks | 
| Tissue metabolism (subcutaneous visceral adipose tissue, skeletal muscle tissue) | Difference in change between the groups regarding receptor expression and metabolic changes in different pathways (lipolysis, insulin signalling etc) | 12 weeks | 
| Microbiome composition and functionality | Difference in change between the groups. Measured using 16S-RNA sequencing and faecal analysis of substrates of saccharolytic and proteolytic fermentation. | 12 weeks | 
| Gastrointestinal side-effects of dietary supplement | Difference in change between the groups. Measured by gastrointestinal symptom rating scale and questionnaires on general wellbeing. Gastro-intestinal symptom rating scale: 15 questions on 7-point Likert scale (1 = strongly disagree; 7 = strongly agree) | 12 weeks | 
| Stool consistency | Difference in change between the groups. Measured by bristol stool scale (7-point scale (1 = solid feces, 7 = severe diarrhoea) | 12 weeks |