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NCT Number: 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

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.

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Key information

Conditions

Diabetes Mellitus Type 2 Diabetes Mellitus Diabetes Mellitus, Type 2 Digestive System Diseases Endocrine System Diseases Fatty Liver Glucose Metabolism Disorders Liver Diseases Metabolic Diseases Non-alcoholic Fatty Liver Disease Nutritional and Metabolic Diseases

Age range

35 year–70 year

Sex eligibility

Male

Study type

Interventional

Phase

Not applicable

Primary location

Federico II University

Naples, 80131, Italy

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

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.

Primary outcomes

  1. Differences in liver fat content

    Time frame: At baseline and at the end of 6 weeks of each treatment

    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).

Secondary outcomes

  1. Differences in glycemic variability

    Time frame: At baseline and at the end of 6 weeks of each treatment

    Differences in glycemic variability after the intake of polyphenol rich drink (RGPD) for 6 weeks, as compared to control drink (placebo). Glycemic variability will be assessed by Continuos Glucose Monitoring (CGM) during the 7 days before the end of each treatment.

  2. Differences in glucose response

    Time frame: At the end of 6 weeks of each treatment

    Differences in fasting and postprandial plasma glucose response to a standard test meal at the end of the 6-week treatment with polyphenol rich drink (RGPD) as compared to control drink (placebo). Plasma glucose concentration will be assessed by enzymatic colorimetric methods.

  3. Differences in insulin response

    Time frame: At the end of 6 weeks of each treatment

    Differences in fasting and postprandial plasma insulin response to a standard test meal at the end of the 6-week treatment with polyphenol rich drink (RGPD) as compared to control drink (placebo). Plasma insulin concentration will be assessed by ELISA method.

  4. Differences in fasting lipid concentrations

    Time frame: At the end of 6 weeks of each treatment

    Differences in fasting plasma triglycerides, total cholesterol, HDL-cholesterol and LDL-cholesterol concentration at the end of the 6-week treatment with polyphenol rich drink (RGPD) as compared to control drink (placebo). Plasma lipid concentrations will be assessed by enzymatic colorimetric methods.

  5. Differences in postprandial triglyceride response

    Time frame: At the end of 6 weeks of each treatment

    Differences in postprandial plasma triglycerides concentration at the end of the 6-week treatment with polyphenol rich drink (RGPD) as compared to control drink (placebo). Plasma triglyceride concentrations will be assessed by enzymatic colorimetric methods.

  6. Differences in gastrointestinal hormones response

    Time frame: At the end of 6 weeks of each treatment

    Differences in fasting and postprandial plasma GLP-1, PYY and Ghrelin concentration at the end of the 6-week treatment with polyphenol rich drink (RGPD) as compared to control drink (placebo). Plasma concentrations of GLP-1, PYY and Ghrelin will be assessed by ELISA methods.

  7. Differences in inflammatory markers

    Time frame: At the end of 6 weeks of each treatment

    Differences in fasting and postprandial serum hs-CRP concentration at the end of the 6-week treatment with polyphenol rich drink (RGPD) as compared to control drink (placebo). Serum concentrations of hs-CRP will be assessed by immunoturbidimetric method.

  8. Differences in gut microbiota composition

    Time frame: At the end of 6 weeks of each treatment

    Differences in microbiota composition at the end of the 6-week treatment with polyphenol rich drink (RGPD) as compared to control drink (placebo). Microbiota analysis will be assessed on feacal samples by metagenomics.

Sponsors and collaborators

Lead sponsor

Federico II University

Other

Collaborators

  • Fondazione C.N.R./Regione Toscana "G. Monasterio", Pisa, Italy

Registry information

Acronym: PoLiFat

Important dates

Study start
2024
Primary completion
2025
Study completion
2025
First posted
Mar 26, 2025
Registry last updated
Mar 26, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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