Clinical trial NCT05354245: Using a Complex Carbohydrate Mixture to Steer Fermentation and Improve Metabolism in Adults With Overweight and Prediabetes (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
Overall status: COMPLETED
Phase: NA
Conditions: Insulin Resistance
Impaired Glucose Tolerance
PreDiabetes
Overweight and Obesity
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: Carbohydrate Competence Center
First posted: 2022-04-29
Enrollment: 44
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Peripheral insulin sensitivity
timeFrame: 12 weeks
Secondary outcomes:
measure: Insulin sensitivity (hepatic and adipose tissue)
timeFrame: 12 weeks
measure: Gut permeability
timeFrame: 12 weeks
measure: Inflammation
timeFrame: 12 weeks
measure: Energy and substrate metabolism
timeFrame: 12 weeks
measure: Neurocognitive functioning
timeFrame: 12 weeks
measure: Food reward related brain activity
timeFrame: 12 weeks
measure: Tissue metabolism (subcutaneous visceral adipose tissue, skeletal muscle tissue)
timeFrame: 12 weeks
measure: Microbiome composition and functionality
timeFrame: 12 weeks
measure: Gastrointestinal side-effects of dietary supplement
timeFrame: 12 weeks
measure: Stool consistency
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University
Study officials:
affiliation: Maastricht University
name: Ellen E Blaak, Prof.Dr.
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.