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

Primary Purpose

Insulin Resistance, Impaired Glucose Tolerance, PreDiabetes

Status

Recruiting

Phase

Not Applicable

Locations

Netherlands

Study Type

Interventional

Intervention

Fibre supplement (potato-pectin)

Placebo

High-protein diet

About this trial

This is an interventional treatment trial for Insulin Resistance

Eligibility Criteria

30 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

Maastricht UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Fibre mixture group

Placebo group

Arm Description

Use of a fibre mixture (3 times daily, 5 grams per gift, total of 15 grams per day) during 12 weeks

Use of a placebo (maltodextrin, isocaloric manner, 3 times daily) during 12 weeks.

Outcomes

Primary Outcome Measures

Peripheral insulin sensitivity

Change in peripheral insulin sensitivity between the two groups. Measured using a two-step hyperinsulinemic-euglycemic clamp

Secondary Outcome Measures

Insulin sensitivity (hepatic and adipose tissue)

Change in insulin sensitivity between the two groups. Measured using a two-step hyperinsulinemic-euglycemic clamp

Gut permeability

Difference in change between the groups. Measured using multisugar test

Inflammation

Difference in change between the groups. Measured using serum values.

Energy and substrate metabolism

Difference in change between the groups. Measured using serum values (circulating metabolites) and indirect calorimetry (energy harvest and expenditure)

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.

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

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)

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.

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)

Stool consistency

Difference in change between the groups. Measured by bristol stool scale (7-point scale (1 = solid feces, 7 = severe diarrhoea)

Full Information

NCT ID

NCT05354245

First Posted

February 22, 2022

Last Updated

January 11, 2023

Sponsor

Maastricht University

Collaborators

Carbohydrate Competence Center

1. Study Identification

Unique Protocol Identification Number

NCT05354245

Brief Title

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

Acronym

DISTAL

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Recruiting

Study Start Date

September 8, 2022 (Actual)

Primary Completion Date

December 2024 (Anticipated)

Study Completion Date

December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Maastricht University

Collaborators

Carbohydrate Competence Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

44 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Fibre mixture group

Arm Type

Experimental

Arm Description

Use of a fibre mixture (3 times daily, 5 grams per gift, total of 15 grams per day) during 12 weeks

Arm Title

Placebo group

Arm Type

Placebo Comparator

Arm Description

Use of a placebo (maltodextrin, isocaloric manner, 3 times daily) during 12 weeks.

Intervention Type

Dietary Supplement

Intervention Name(s)

Fibre supplement (potato-pectin)

Intervention Description

Fibre supplement

Intervention Type

Dietary Supplement

Intervention Name(s)

Placebo

Other Intervention Name(s)

Maltodextrin

Intervention Description

Maltodextrin

Intervention Type

Dietary Supplement

Intervention Name(s)

High-protein diet

Intervention Description

High-protein diet

Primary Outcome Measure Information:

Title

Peripheral insulin sensitivity

Description

Change in peripheral insulin sensitivity between the two groups. Measured using a two-step hyperinsulinemic-euglycemic clamp

Time Frame

12 weeks

Secondary Outcome Measure Information:

Title

Insulin sensitivity (hepatic and adipose tissue)

Description

Change in insulin sensitivity between the two groups. Measured using a two-step hyperinsulinemic-euglycemic clamp

Time Frame

12 weeks

Title

Gut permeability

Description

Difference in change between the groups. Measured using multisugar test

Time Frame

12 weeks

Title

Inflammation

Description

Difference in change between the groups. Measured using serum values.

Time Frame

12 weeks

Title

Energy and substrate metabolism

Description

Difference in change between the groups. Measured using serum values (circulating metabolites) and indirect calorimetry (energy harvest and expenditure)

Time Frame

12 weeks

Title

Neurocognitive functioning

Description

Time Frame

12 weeks

Title

Food reward related brain activity

Description

Time Frame

12 weeks

Title

Tissue metabolism (subcutaneous visceral adipose tissue, skeletal muscle tissue)

Description

Difference in change between the groups regarding receptor expression and metabolic changes in different pathways (lipolysis, insulin signalling etc)

Time Frame

12 weeks

Title

Microbiome composition and functionality

Description

Difference in change between the groups. Measured using 16S-RNA sequencing and faecal analysis of substrates of saccharolytic and proteolytic fermentation.

Time Frame

12 weeks

Title

Gastrointestinal side-effects of dietary supplement

Description

Time Frame

12 weeks

Title

Stool consistency

Description

Difference in change between the groups. Measured by bristol stool scale (7-point scale (1 = solid feces, 7 = severe diarrhoea)

Time Frame

12 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

30 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Colin AJ van Kalkeren, M.D.

Phone

+31 (0)43 3881638

c.vankalkeren@maastrichtuniversity.nl

First Name & Middle Initial & Last Name or Official Title & Degree

Thirza van Deuren, MSc

Phone

+31(0)433881638

t.vandeuren@maastrichtuniversity.nl

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ellen E Blaak, Prof.Dr.

Organizational Affiliation

Maastricht University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Maastricht University

City

Maastricht

ZIP/Postal Code

6229ER

Country

Netherlands

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Colin van Kalkeren, MD

Phone

+31(0)433881638

c.vankalkeren@maastrichtuniversity.nl

First Name & Middle Initial & Last Name & Degree

Thirza van Deuren, MSc

Phone

+31(0)433881638

t.vandeuren@maastrichtuniversity.nl

First Name & Middle Initial & Last Name & Degree

Ellen Blaak, Prof.Dr.Ing

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

32122428

Citation

Blaak EE. Current metabolic perspective on malnutrition in obesity: towards more subgroup-based nutritional approaches? Proc Nutr Soc. 2020 Aug;79(3):331-337. doi: 10.1017/S0029665120000117. Epub 2020 Mar 3.

Results Reference

background

PubMed Identifier

32865024

Citation

Blaak EE, Canfora EE, Theis S, Frost G, Groen AK, Mithieux G, Nauta A, Scott K, Stahl B, van Harsselaar J, van Tol R, Vaughan EE, Verbeke K. Short chain fatty acids in human gut and metabolic health. Benef Microbes. 2020 Sep 1;11(5):411-455. doi: 10.3920/BM2020.0057. Epub 2020 Aug 31.

Results Reference

background

PubMed Identifier

26260141

Citation

Canfora EE, Jocken JW, Blaak EE. Short-chain fatty acids in control of body weight and insulin sensitivity. Nat Rev Endocrinol. 2015 Oct;11(10):577-91. doi: 10.1038/nrendo.2015.128. Epub 2015 Aug 11.

Results Reference

background

PubMed Identifier

30670819

Citation

Canfora EE, Meex RCR, Venema K, Blaak EE. Gut microbial metabolites in obesity, NAFLD and T2DM. Nat Rev Endocrinol. 2019 May;15(5):261-273. doi: 10.1038/s41574-019-0156-z.

Results Reference

background

PubMed Identifier

28539646

Citation

Canfora EE, van der Beek CM, Jocken JWE, Goossens GH, Holst JJ, Olde Damink SWM, Lenaerts K, Dejong CHC, Blaak EE. Colonic infusions of short-chain fatty acid mixtures promote energy metabolism in overweight/obese men: a randomized crossover trial. Sci Rep. 2017 May 24;7(1):2360. doi: 10.1038/s41598-017-02546-x.

Results Reference

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

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