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

NCT06895018 | Enrolling By Invitation

• 1 other identifier: 325/20
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Mellitus Type 2

Keywords

Polyphenols; NAFLD; Gut microbiota; Glucose metabolism; insulin metabolism; lipid metabolism; glucose variability; sublinical inflammation; grape pomace

Outcome Measures

Primary Outcomes (1)

• Differences in liver fat content

  Differences in liver fat content after the intake of polyphenol rich drink (RGPD) for 6 weeks, as compared to Control drink (Placebo). Liver fat content will be assessed by magnetic resonance spectroscopy (MRI).

  At baseline and at the end of 6 weeks of each treatment

Secondary Outcomes (8)

• Differences in glycemic variability

  At baseline and at the end of 6 weeks of each treatment

• Differences in glucose response

  At the end of 6 weeks of each treatment

• Differences in insulin response

  At the end of 6 weeks of each treatment

• Differences in fasting lipid concentrations

  At the end of 6 weeks of each treatment

• Differences in postprandial triglyceride response

  At the end of 6 weeks of each treatment

Study Arms (2)

Grape Pomace Polyphenol Rich Drink

EXPERIMENTAL

Participants consume an experimental drink rich in polyphenols extracted from red grape pomace (RGP) containing 1.5 g/150 ml of Gallic Acid Equivalent (GAE) polyphenols and 28 g/150 ml of soluble sugars (14 g of glucose and 14 g of fructose) during the lunch and dinner for 6 weeks

Dietary Supplement: Supplementation with Polyphenol Rich Drink

Placebo Drink

PLACEBO COMPARATOR

Participants consume a control drink (Placebo), containing zero polyphenol and 28 g of total sugars (14 g of glucose and 14 g of fructose solubilized in 150 ml of drinking water), quantities equivalent to those contained in the experimental drink, during the lunch and dinner for 6 weeks

Dietary Supplement: Supplementation with Control Drink (Placebo)

Interventions

Supplementation with Polyphenol Rich Drink DIETARY_SUPPLEMENT

Participants were instructed to consume, over a 6-week period, within the context of a Mediterranean diet, a polyphenol-rich drink RGPD (150 mL) containing 1.5 g of polyphenols. After this treatment period, participants underwent a two-week washout period before switching to the alternative treatment with control drink (Placebo) devoid of polyphenols. To evaluate metabolic responses during both fasting and postprandial states, participants participants consumed a standardized test meal at the end of the 6 weeks. This standard meal was preceded by the consumption of the RGPD 60 minutes prior.

Grape Pomace Polyphenol Rich Drink

Supplementation with Control Drink (Placebo) DIETARY_SUPPLEMENT

Participants were instructed to consume, over a 6-week period, within the context of a Mediterranean diet, a control drink (Placebo) (150 mL) containing 0 g of polyphenols. After this treatment period, participants underwent a two-week washout period before switching to the alternative treatment with a polyphenol-rich drink RGPD (150 mL) containing 1.5 g of polyphenols. To evaluate metabolic responses during both fasting and postprandial states, participants participants consumed a standardized test meal at the end of the 6 weeks. This standard meal was preceded by the consumption of the Control drink (Placebo) 60 minutes prior.

Placebo Drink

Eligibility Criteria

• Age: 35 Years - 70 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Federico II University: lead
• Fondazione C.N.R./Regione Toscana "G. Monasterio", Pisa, Italy: collaborator

Study Sites (1)

Federico II University

Napoli, 80131, Italy

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Non-alcoholic Fatty Liver Disease

Interventions

Dietary Supplements

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Rosalba Giacco, Senior Researcher

  CNR

  PRINCIPAL INVESTIGATOR

• Luigi Russo, Senior Researcher

  CNR

  STUDY DIRECTOR

• Lutgarda Bozzetto, Full Professor

  Federico II Univerisity

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Academic Researcher

Study Record Dates

• First Submitted: March 19, 2025
• First Posted: March 26, 2025
• Study Start: May 3, 2024
• Primary Completion: August 8, 2025
• Study Completion: October 31, 2025
• Last Updated: March 26, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

IT (1)