Clinical trial NCT05654805: Nutraceutical Improvement of Glucose Metabolism, NAFLD and Insulin Resistance by Oat-fiber Supplementation in Type 2 Diabetes Mellitus Patients
Official title: Nutraceutical Improvement of Glucose Metabolism, NAFLD and Insulin Resistance by Oat-fiber Supplementation in Type 2 Diabetes Mellitus Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Type 2 Diabetes
NAFLD
Keywords: insoluble cereal fiber
insulin resistance
glucose tolerance
inflammation
incretins
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Wilhelm-Doerenkamp-Foundation (Funding)
First posted: 2022-12-16
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: parallel-designed triple-blinded randomised placebo-controlled intervention study
Primary purpose: TREATMENT

Brief summary: Cohort studies show an association between increased intake of insoluble (cereal) fiber and decreased risk for cardiovascular disease, type 2 diabetes (T2DM), non-alcoholic fatty liver disease (NAFLD), cancer, infectious and inflammatory disorders. Intervention studies, specifically addressing non-fermentable carbohydrates instead of their food sources (whole grain, pulses, legumes) are still sparse. Whole grain trials reported beneficial effects, but cannot pinpoint these benefits on fiber, as minerals, vitamins, grain protein and food matrix contribute to the metabolic results.

The antidiabetic effectiveness of cereal fiber might be explained by a) an increased secretion of incretins and other glucose-induced gastrointestinal hormones, b) an alteration of the gut microbiome, or c) a fermentation to short-chain fatty acids. Fermentable fibers (most of which are soluble) show these mechanisms, but lack strong diabetes-protective associations in cohort studies. In recent supplementation trials, insoluble, mostly non-fermentable fibers improved insulin resistance, glycemia and inflammation in patients with metabolic syndrome or prediabetes.

Between 2022-2024, we want to assess the effectiveness of insoluble, poorly fermentable cereal fiber in a shorter Intervention period in patients with high responsiveness (insulin-naïve overt type 2 diabetes mellitus with insulin resistance and NAFLD), using a fiber drinking supplement. Our triple-blinded RCT compares the metabolic effects and mechanistic outcomes of isocaloric treatments with 15 grams of oat-fiber supplement per day (vs. placebo) in 92 patients, covering an intervention period of 12 weeks.

Detailed description: Cohort studies show an association between increased intake of insoluble (cereal) fiber and decreased risk for cardiovascular disease, type 2 diabetes (T2DM), non-alcoholic fatty liver disease (NAFLD), cancer, infectious and inflammatory disorders. Intervention studies, specifically addressing non-fermentable carbohydrates instead of their food sources (whole grain, pulses, legumes) are still sparse. Whole grain trials reported beneficial effects, but cannot pinpoint these benefits on fiber, as minerals, vitamins, grain protein and food matrix contribute to the metabolic results.

The antidiabetic effectiveness of cereal fiber might be explained by a) an increased secretion of incretins and other glucose-induced gastrointestinal hormones, b) an alteration of the gut microbiome, or c) a fermentation to short-chain fatty acids. Fermentable fibers (most of which are soluble) show these mechanisms, but lack strong diabetes-protective associations in cohort studies. In recent supplementation trials, insoluble, mostly non-fermentable fibers improved insulin resistance, glycemia and inflammation in patients with metabolic syndrome or prediabetes.

Between 2022-2024, we want to assess the effectiveness of insoluble, poorly fermentable cereal fiber in a shorter Intervention period in patients with high responsiveness (insulin-naïve overt type 2 diabetes mellitus with insulin resistance and NAFLD), using an oat fiber drinking supplement. Our triple-blinded RCT compares the metabolic effects and mechanistic outcomes of isocaloric treatments with 15 grams of oat-fiber supplement per day (vs. placebo) in 92 patients, covering an intervention period of 12 weeks.

Eligibility criteria: Inclusion Criteria:

* type 2 diabetes mellitus
* HOMA-IR \> 2.5
* NAFLD (MR-S \> 5,56 %)

Exclusion Criteria:

* insulin treatment
* diabetes type 1, 3 or 4
* severe cardiopulmonary, renal, inflammatory, gastrointestinal, psychiatric or endocrine disorder
* alcohol abuse or excess alcohol intake
* recent CVD event (\< 3months)
* relevant liver disease other than NAFLD
* current cancer diagnosis or treatment
* allergy or incompatibility to the supplement

Primary outcomes:
measure: change in liver fat content (MRS)
timeFrame: 12 weeks
measure: change in glucose tolerance (mixed-meal test)
timeFrame: 12 weeks
measure: change in insulin resistance (Matsuda)
timeFrame: 12 weeks
Secondary outcomes:
measure: change in fasting glucose
timeFrame: 12 weeks
measure: change in HbA1c
timeFrame: 12 weeks
measure: change in inflammation parameters (CRP, leucocytes, IL-6, IL-1ß, IL-18, IL-10, IL-22
timeFrame: 12 weeks
measure: change in incretins (GLP-1, GIP, PYY)
timeFrame: 12 weeks
measure: change in FGF21
timeFrame: 12 weeks
measure: change in IGF-1 and its binding proteins
timeFrame: 12 weeks
Other outcomes:
measure: change in secondary GI peptide hormons (GLP-2, PP, ghrelin, CCK)
timeFrame: 12 weeks
measure: change in fasting serum amino acid pattern
timeFrame: 12 weeks
measure: change in faecal excretion of BCAA metabolites
timeFrame: 12 weeks
Locations:
city: Berlin
country: Germany
facility: Charite University Hospital Berlin
Study officials:
affiliation: Study physician
name: Stefan Kabisch, Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: