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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Insulin Resistance; PreDiabetes; Overweight and Obesity; Impaired Glucose Tolerance
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Fibre supplement (potato-pectin); Dietary supplement: High-protein diet

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 Type: Interventional
• Enrollment (Estimated): 44
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Colin AJ van Kalkeren, M.D.; Phone Number: +31 (0)43 3881638; Email: c.vankalkeren@maastrichtuniversity.nl
• Study Contact Backup: Name: Thirza van Deuren, MSc; Phone Number: +31(0)433881638; Email: t.vandeuren@maastrichtuniversity.nl

Study Locations

• Netherlands
  • Maastricht, Netherlands, 6229ER
    • Recruiting
    • Maastricht University
    • Contact: Thirza van Deuren, MSc; Phone Number: +31(0)433881638; Email: t.vandeuren@maastrichtuniversity.nl
    • Contact: Colin van Kalkeren, MD; Phone Number: +31(0)433881638; Email: c.vankalkeren@maastrichtuniversity.nl
    • Principal Investigator: Ellen Blaak, Prof.Dr.Ing

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fibre mixture group; 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); Fibre supplement; Dietary supplement: High-protein diet; High-protein diet
Placebo Comparator: Placebo group; Use of a placebo (maltodextrin, isocaloric manner, 3 times daily) during 12 weeks.	Dietary supplement: Placebo; Maltodextrin; Other Names: Maltodextrin; Dietary supplement: High-protein diet; High-protein diet

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Collaborators: Carbohydrate Competence Center
• Investigators: Principal Investigator: Ellen E Blaak, Prof.Dr., Maastricht University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2022
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: February 22, 2022
• First Submitted That Met QC Criteria: April 26, 2022
• First Posted (Actual): April 29, 2022

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Overnutrition; Nutrition Disorders; Body Weight; Hyperinsulinism; Hyperglycemia; Prediabetic State; Glucose Intolerance; Insulin Resistance; Overweight
• Other Study ID Numbers: NL80459.068.22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No