Clinical trial NCT06895018: Medium-term Effects of a Polyphenol-rich Beverage Based on Red Grape Pomace Extract on Non-alcoholic Fatty Liver Disease, Cardiometabolic Risk Profile and Gut Microbiota in Subjects with Type 2 Diabetes
Official title: Medium-term Effects of a Polyphenol-rich Beverage Based on Red Grape Pomace Extract on Non-alcoholic Fatty Liver Disease, Cardiometabolic Risk Profile and Gut Microbiota in Subjects with Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Diabetes Mellitus Type 2
Keywords: Polyphenols
NAFLD
Gut microbiota
Glucose metabolism
insulin metabolism
lipid metabolism
glucose variability
sublinical inflammation
grape pomace
Lead sponsor: Federico II University
Sponsor class: OTHER
Collaborators: name: Fondazione C.N.R./Regione Toscana "G. Monasterio", Pisa, Italy
First posted: 2025-03-26
Enrollment: 20
Sex: MALE
Minimum age (years): 35
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Nonalcoholic fatty liver disease (NAFLD) is a liver disease characterized by an abnormal accumulation of fat not due to alcohol or drug consumption that can evolve into steatohepatitis (NASH), fibrosis and cirrhosis. Its prevalence is high, affecting approximately 20-30% of the general adult population and is also growing in pediatric age. Obesity, insulin resistance and type 2 diabetes (T2DM) are common and well-known risk factors for NAFLD, which is approximately 2-3 times more prevalent among obese and diabetic individuals. Despite the high and increasing prevalence of NAFLD in the population, its pathophysiology is not fully understood and there is currently no pharmacological treatment available.

Recent evidence suggests that dietary polyphenols may have specific beneficial effects on hepatic steatosis and associated sequelae by polyphenol metabolites and their phase II derivatives. Therefore, the aim of our study is to evaluate whether medium-term consumption of a beverage rich in polyphenols extracted from red grape pomace is able to exert beneficial effects on hepatic steatosis, cardiometabolic risk profile and microbiota composition of patients with type 2 diabetes.

Detailed description: A randomized, crossover, placebo-controlled study will be conducted. Twenty patients with type 2 diabetes mellitus (T2DM) recruited from the Diabetes Unit of the University Hospital of Naples "Federico II" who meet the inclusion criteria will be studied. After a 2-week run-in period during which they will stabilize their habitual diet, participants will be randomly assigned to receive either 150 ml/day of a polyphenol-rich red grape pomace beverage (RG) or 150 ml/day of a control beverage (Placebo) for a 6-week period each. The two treatments will be separated by a 2-week wash-out period.

At the end of the run-in, wash-out, and both treatment periods, participants will undergo fasting blood samples to evaluate key metabolic parameters. After each treatment period (RG or placebo), a standardized meal (960 kcal, 18% protein, 30% fat, 52% carbohydrates) will be administered along with 150 ml of either the polyphenol-rich beverage or the control beverage, for postprandial metabolic evaluations.

At the end of both treatments, hepatic fat content, fasting and postprandial metabolic parameters, microbiota composition and continuos glucose monitoring will be assessed.

Energy intake and habitual dietary composition will be evaluated at the end of the run-in, and at 6 weeks after the start of each treatment period using a 7-day food diary.

Eligibility criteria: Inclusion Criteria:

* Body Mass Index (BMI) \>25 and ≤35 kg/m2
* Cholesterolemia ≤ 250 mg/dl and Triglyceridemia ≤ 200 mg/dl.
* type 2 Diabetes in good glycemic control (Hb1Ac ≤7.5%) treated with diet alone or diet + metformin.

Exclusion Criteria:

* Cardiovascular events (myocardial infarction and/or stroke)
* Renal insufficiency (serum creatinine \>1.5 mg/dl) and liver failure (ALT/AST twice the normal values)
* Anemia (Hb \<12 g/dl) or other chronic disease
* Insulin therapy and other hypoglycemic drugs other than metformin
* Habitual intense physical activity

Primary outcomes:
measure: Differences in liver fat content
timeFrame: At baseline and at the end of 6 weeks of each treatment
Secondary outcomes:
measure: Differences in glycemic variability
timeFrame: At baseline and at the end of 6 weeks of each treatment
measure: Differences in glucose response
timeFrame: At the end of 6 weeks of each treatment
measure: Differences in insulin response
timeFrame: At the end of 6 weeks of each treatment
measure: Differences in fasting lipid concentrations
timeFrame: At the end of 6 weeks of each treatment
measure: Differences in postprandial triglyceride response
timeFrame: At the end of 6 weeks of each treatment
measure: Differences in gastrointestinal hormones response
timeFrame: At the end of 6 weeks of each treatment
measure: Differences in inflammatory markers
timeFrame: At the end of 6 weeks of each treatment
measure: Differences in gut microbiota composition
timeFrame: At the end of 6 weeks of each treatment
Other outcomes:
Locations:
city: Napoli
country: Italy
facility: Federico II University
Study officials:
affiliation: CNR
name: Rosalba Giacco, Senior Researcher
role: PRINCIPAL_INVESTIGATOR
affiliation: CNR
name: Luigi Russo, Senior Researcher
role: STUDY_DIRECTOR
affiliation: Federico II Univerisity
name: Lutgarda Bozzetto, Full Professor
role: PRINCIPAL_INVESTIGATOR
References: