Metabolic Flexibility, Gut Microbiota, Healthy Diet and Exercise in NAFLD on Genetics Base

NCT02951546 | Completed DMC

• 1 other identifier: RIF.CE:4119
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Nonalcoholic fatty liver disease (NAFLD) is associated to obesity, metabolic syndrome and genetic predisposition: specific variants of the genes PNPLA3 and TM6SF2 are the most involved. Also biochemical mechanisms that affect the "metabolic flexibility" need to be better clarified. It is known that a dietary intervention, accompanied by a physical personalized training, reduce either the hepatic fat content either insulin resistance. Therefore, the aim of the study is to evaluate "metabolic flexibility" in obese NAFLD subjects taking in account the presence or absence of PNPLA3 and TM6SF2 polymorphism and the histopathological diagnosis of either simple steatosis or nonalcoholic steatohepatitis (NASH). The composition of gut microbiota will be also evaluated. Finally, two distinct healthy dietary profiles accompanied by a personalized physical training, will be tested to comprehend whether and how "healthy diets" could operate in the clinical treatment of NAFLD and related conditions.

Conditions

Non-alcoholic Fatty Liver Disease; Obesity

Outcome Measures

Primary Outcomes (16)

• Cholesterol assessment

  total cholesterol, HDL- cholesterol, LDL- cholesterol levels reported as mg/dl

  baseline

• Cholesterol assessment

  total cholesterol, HDL- cholesterol, LDL- cholesterol levels reported as mg/dl

  18 weeks after baseline

• triglycerides assessment

  tryglicerides levels reported as mg/dl

  baseline

• triglycerides assessment

  tryglicerides levels reported as mg/dl

  18 weeks after baseline

• metabolic flexibility variation in liver function;

  alanine aminotransferase (ALT) \[U/L\] , aspartate aminotransferase (AST) \[UI/L\]

  baseline

• metabolic flexibility variation in liver function;

  alanine aminotransferase (ALT) \[U/L\] , aspartate aminotransferase (AST) \[UI/L\]

  18 weeks after baseline

• Waist circumference measurements;

  waist circumference reported as cm

  baseline

• Waist circumference measurements;

  waist circumference reported as cm

  18 weeks after baseline

• anthropometric measurements;

  Body mass index reported as kg/m\^2

  baseline

• anthropometric measurements;

  Body mass index reported as kg/m\^2

  18 weeks after baseline

• Ultrasonographic examination;

  Liver ultrasonography according with criteria by Hamaguchi

  baseline

• Ultrasonographic examination;

  Liver ultrasonography according with criteria by Hamaguchi

  18 weeks after baseline

• Glucidic profile

  fasting glucose reported as mg/dl

  baseline

• Glucidic profile

  fasting glucose reported as mg/dl

  18 weeks after baseline

• Insulinemia

  insulin reported as µU/mL

  baseline

• Insulinemia

  insulin reported as µU/mL

  18 weeks after baseline

Study Arms (2)

Mediterranean diet

EXPERIMENTAL

Hypocaloric Mediterranean diet for a 4-month period; Aerobic exercise training for a 4-month period;

Dietary Supplement: Mediterranean diet; Other: Aerobic exercise

Low fat diet

EXPERIMENTAL

Hypocaloric low fat diet supplemented by branched and essential amino acids considering the total protein intake for a 4- month period; Aerobic exercise training for a 4- month period;

Dietary Supplement: Low fat diet; Other: Aerobic exercise

Interventions

Mediterranean diet DIETARY_SUPPLEMENT

In the Mediterranean diet fat intake will be equal to 35% of the total energy intake minus carbohydrate and protein energy carbohydrate as 65% of total calorie intake, dietary cholesterol \<300 mg/day, dietary fiber 25 g/day.

Mediterranean diet

Low fat diet DIETARY_SUPPLEMENT

In the hypocaloric low fat diet, fat will represent less than 25% of the total energy intake. Branched and essential amino acids will be administered taking into account the total protein intake.

Low fat diet

Aerobic exercise OTHER

A personalized program of aerobic exercise will be prescribed to the participants of both arms, following the "FITT" principles (frequency, intensity, time and type).

Low fat diet; Mediterranean diet

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• body mass index (BMI) \> 30 Kg/m2 and \< 40 Kg/m2;
• Caucasian Italian subjects
• hepatic steatosis according with ultrasonographic Hamaguchi's criteria and/or hypertransaminasemia (ALT \>30 IU/L in men and \>20 IU/L in women)

You may not qualify if:

• any malignant disease during the last 5 years;
• any inflammatory or autoimmune disease;
• corticosteroids for systemic use;
• renal failure (GFR\<90 ml/min);
• heart failure (NYHA classes II-IV);
• history of viral or autoimmune liver disease;
• any cause cirrhosis;
• excessive alcohol intake (\>140g/week for men and 70g/week for women);
• participation in a reducing-weight program in the last 3 months;
• level of physical activity higher than 3 METs;
• therapy with antibiotics during the last 3 months;
• bile salts, cholestyramine during the last 6 months before enrollment;
• previous cholecystectomy;
• gallbladder disease

Sponsors & Collaborators

• University of Roma La Sapienza: lead
• Bambino Gesù Hospital and Research Institute: collaborator
• Università degli studi di Roma Foro Italico: collaborator
• Göteborg University: collaborator

Study Sites (1)

Department of Translational and Precision Medicine, Sapienza University of Rome, Umberto I Hospital

Rome, 00185, Italy

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Obesity

Interventions

Diet, Mediterranean; Diet, Fat-Restricted; Exercise

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diet, Plant-Based; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Stefano Ginanni Corradini, MD, PhD

  Department Translational and Precision Medicine, Sapienza University of Rome

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Nonalcoholic fatty liver disease (NAFLD) is associated to obesity, metabolic syndrome and genetic predisposition: specific variants of the genes PNPLA3 and TM6SF2 are the most involved. Also biochemical mechanisms that affect the "metabolic flexibility" need to be better clarified. It is known that a dietary intervention and a physical personalized training, reduce either the hepatic fat content either insulin resistance. Therefore, the aim of the study is to evaluate "metabolic flexibility" in obese NAFLD subjects taking in account the presence or absence of PNPLA3 and TM6SF2 polymorphism and the histopathological diagnosis of either simple steatosis or nonalcoholic steatohepatitis (NASH). The composition of gut microbiota will be also evaluated. Finally, two distinct healthy dietary profiles accompanied by a personalized physical training, will be tested to comprehend whether and how "healthy diets" could operate in the clinical treatment of NAFLD and related conditions.

Study Record Dates

• First Submitted: October 26, 2016
• First Posted: November 1, 2016
• Study Start: October 1, 2016
• Primary Completion: September 1, 2021
• Study Completion: February 1, 2022
• Last Updated: May 27, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)