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

Not Applicable

Completed

• Conditions: Insulin Resistance; Impaired Glucose Tolerance; PreDiabetes; Overweight and Obesity
• Interventions: Dietary Supplement: Fibre supplement (potato-pectin); Dietary Supplement: Placebo; Dietary Supplement: High-protein diet

• Registration Number: NCT05354245
• Lead Sponsor: Maastricht University Medical Center

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2022-02-22
• Study First Submitted QC: 2022-04-26
• Study First Posted: 2022-04-29
• Study Start: 2022-09-08
• Status Verified: 2024-06
• Primary Completion: 2024-06-10
• Study Completion: 2024-06-10
• Last Update Submitted: 2024-06-26
• Last Update Posted: 2024-06-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 44

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fibre mixture group	High-protein diet	Use of a fibre mixture (3 times daily, 5 grams per gift, total of 15 grams per day) during 12 weeks
Placebo group	High-protein diet	Use of a placebo (maltodextrin, isocaloric manner, 3 times daily) during 12 weeks.
Fibre mixture group	Fibre supplement (potato-pectin)	Use of a fibre mixture (3 times daily, 5 grams per gift, total of 15 grams per day) during 12 weeks
Placebo group	Placebo	Use of a placebo (maltodextrin, isocaloric manner, 3 times daily) during 12 weeks.

Primary Outcome Measures

Name	Time	Method
Peripheral insulin sensitivity	12 weeks	Change in peripheral insulin sensitivity between the two groups. Measured using a two-step hyperinsulinemic-euglycemic clamp

Secondary Outcome Measures

Name	Time	Method
Inflammation	12 weeks	Difference in change between the groups. Measured using serum values.
Food reward related brain activity	12 weeks	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
Energy and substrate metabolism	12 weeks	Difference in change between the groups. Measured using serum values (circulating metabolites) and indirect calorimetry (energy harvest and expenditure)
Neurocognitive functioning	12 weeks	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.
Tissue metabolism (subcutaneous visceral adipose tissue, skeletal muscle tissue)	12 weeks	Difference in change between the groups regarding receptor expression and metabolic changes in different pathways (lipolysis, insulin signalling etc)
Insulin sensitivity (hepatic and adipose tissue)	12 weeks	Change in insulin sensitivity between the two groups. Measured using a two-step hyperinsulinemic-euglycemic clamp
Gut permeability	12 weeks	Difference in change between the groups. Measured using multisugar test
Microbiome composition and functionality	12 weeks	Difference in change between the groups. Measured using 16S-RNA sequencing and faecal analysis of substrates of saccharolytic and proteolytic fermentation.
Gastrointestinal side-effects of dietary supplement	12 weeks	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)
Stool consistency	12 weeks	Difference in change between the groups. Measured by bristol stool scale (7-point scale (1 = solid feces, 7 = severe diarrhoea)

Trial Locations

Locations (1)

Maastricht University; 🇳🇱 Maastricht, Netherlands