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

Insulin Resistance Clinical Trial

— DISTAL  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05354245
• Other study ID #: NL80459.068.22
• Status: Recruiting
• Phase: N/A
• Start date: September 8, 2022
• Est. completion date: December 2024

Study information

• Verified date: April 2024
• Source: Maastricht University Medical Center
• Contact: Colin AJ van Kalkeren, M.D.
• Phone: +31 (0)43 3881638
• Email: c.vankalkeren[@]maastrichtuniversity.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 44
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 30 Years to 75 Years

Eligibility

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 ß-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.

Related Conditions & MeSH terms

• Glucose Intolerance
• Impaired Glucose Tolerance
• Insulin Resistance
• Overweight
• Overweight and Obesity
• PreDiabetes
• Prediabetic State

Intervention

Dietary Supplement:
• Fibre supplement (potato-pectin)
Fibre supplement
• Placebo
Maltodextrin
• High-protein diet
High-protein diet

Locations

Country	Name	City	State
Netherlands	Maastricht University	Maastricht

Sponsors (2)

Lead Sponsor	Collaborator
Maastricht University Medical Center	Carbohydrate Competence Center

Country where clinical trial is conducted

Netherlands, 

References & Publications (5)

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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peripheral insulin sensitivity	Change in peripheral insulin sensitivity between the two groups. Measured using a two-step hyperinsulinemic-euglycemic clamp	12 weeks
Secondary	Insulin sensitivity (hepatic and adipose tissue)	Change in insulin sensitivity between the two groups. Measured using a two-step hyperinsulinemic-euglycemic clamp	12 weeks
Secondary	Gut permeability	Difference in change between the groups. Measured using multisugar test	12 weeks
Secondary	Inflammation	Difference in change between the groups. Measured using serum values.	12 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Stool consistency	Difference in change between the groups. Measured by bristol stool scale (7-point scale (1 = solid feces, 7 = severe diarrhoea)	12 weeks