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OpenTrials
Completed

NCT Number: NCT02951546

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

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.

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Key information

Conditions

Non-Alcoholic Fatty Liver Disease Body Weight Digestive System Diseases Fatty Liver Liver Diseases Nutrition Disorders Nutritional and Metabolic Diseases Obesity Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

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

Rome, 00185, Italy

About this study

Nonalcoholic fatty liver disease (NAFLD) is frequently associated to obesity and metabolic syndrome. In NAFLD, a heritable component to disease susceptibility has been demonstrated: the variants of the genes PNPLA3 and TM6SF2 are the most involved genetic determinants.

To date, biochemical mechanisms that affect the "metabolic flexibility" in obese NAFLD subjects, in presence or absence of genetic susceptibility, need to be better clarified.

Different studies demonstrated that a dietary intervention, accompanied by a physical personalized training, significantly reduce either the hepatic fat content either insulin resistance in overweight and obese subjects, independently of weight loss.

On these bases, the aim of the study is to evaluate "metabolic flexibility" in obese NAFLD subjects taking in account their genetics (presence or absence of PNPLA3 and TM6SF2 polymorphisms) and the histopathological diagnosis of either simple steatosis or nonalcoholic steatohepatitis (NASH). In addition, the composition of gut microbiota will be evaluated.

Finally, in this study, two distinct healthy dietary profiles accompanied by a personalized physical training, will be tested in order to comprehend whether and how "healthy diets" could be effective not only in the prevention, but also in the clinical treatment of NAFLD and other related conditions.

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

  • 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)

Exclusion criteria

  • 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

Treatment and study plan

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.

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.

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).

Primary outcomes

  1. Cholesterol assessment

    Time frame: baseline

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

  2. Cholesterol assessment

    Time frame: 18 weeks after baseline

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

  3. triglycerides assessment

    Time frame: baseline

    tryglicerides levels reported as mg/dl

  4. triglycerides assessment

    Time frame: 18 weeks after baseline

    tryglicerides levels reported as mg/dl

  5. metabolic flexibility variation in liver function;

    Time frame: baseline

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

  6. metabolic flexibility variation in liver function;

    Time frame: 18 weeks after baseline

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

  7. Waist circumference measurements;

    Time frame: baseline

    waist circumference reported as cm

  8. Waist circumference measurements;

    Time frame: 18 weeks after baseline

    waist circumference reported as cm

  9. anthropometric measurements;

    Time frame: baseline

    Body mass index reported as kg/m^2

  10. anthropometric measurements;

    Time frame: 18 weeks after baseline

    Body mass index reported as kg/m^2

  11. Ultrasonographic examination;

    Time frame: baseline

    Liver ultrasonography according with criteria by Hamaguchi

  12. Ultrasonographic examination;

    Time frame: 18 weeks after baseline

    Liver ultrasonography according with criteria by Hamaguchi

  13. Glucidic profile

    Time frame: baseline

    fasting glucose reported as mg/dl

  14. Glucidic profile

    Time frame: 18 weeks after baseline

    fasting glucose reported as mg/dl

  15. Insulinemia

    Time frame: baseline

    insulin reported as µU/mL

  16. Insulinemia

    Time frame: 18 weeks after baseline

    insulin reported as µU/mL

Sponsors and collaborators

Lead sponsor

University of Roma La Sapienza

Other

Collaborators

  • Bambino Gesù Hospital and Research Institute
  • Göteborg University
  • Università degli studi di Roma Foro Italico

Registry information

Official study title

Body Composition, Adiposity Phenotype, Metabolic Flexibility, and Gut Microbiota in PNPLA3 and TM6SF2 Gene Variant Carriers and Non-carriers With Nonalcoholic Fatty Liver Disease. Effects of a Nutritional Intervention Combined to Exercise

Important dates

Study start
2016
Primary completion
2021
Study completion
2022
First posted
Nov 1, 2016
Registry last updated
May 27, 2022

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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