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

Not Applicable

Completed

• Conditions: Obesity; Non-alcoholic Fatty Liver Disease
• Interventions: Dietary Supplement: Mediterranean diet; Dietary Supplement: Low fat diet; Other: Aerobic exercise

• Registration Number: NCT02951546
• Lead Sponsor: University of Roma La Sapienza

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.

Detailed Description

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.

Study Timeline

• Study Start: 2016-10
• Study First Submitted: 2016-10-26
• Study First Submitted QC: 2016-10-28
• Study First Posted: 2016-11-01
• Primary Completion: 2021-09
• Study Completion: 2022-02
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-26
• Last Update Posted: 2022-05-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 120

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Mediterranean diet	Mediterranean diet	Hypocaloric Mediterranean diet for a 4-month period; Aerobic exercise training for a 4-month period;
Low fat diet	Aerobic exercise	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;
Mediterranean diet	Aerobic exercise	Hypocaloric Mediterranean diet for a 4-month period; Aerobic exercise training for a 4-month period;
Low fat diet	Low fat diet	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;

Primary Outcome Measures

Name	Time	Method
Waist circumference measurements;	18 weeks after baseline	waist circumference reported as cm
Insulinemia	18 weeks after baseline	insulin reported as µU/mL
triglycerides assessment	18 weeks after baseline	tryglicerides levels reported as mg/dl
Glucidic profile	18 weeks after baseline	fasting glucose reported as mg/dl
Cholesterol assessment	18 weeks after baseline	total cholesterol, HDL- cholesterol, LDL- cholesterol levels reported as mg/dl
metabolic flexibility variation in liver function;	18 weeks after baseline	alanine aminotransferase (ALT) \[U/L\] , aspartate aminotransferase (AST) \[UI/L\]
anthropometric measurements;	18 weeks after baseline	Body mass index reported as kg/m\^2
Ultrasonographic examination;	18 weeks after baseline	Liver ultrasonography according with criteria by Hamaguchi

Trial Locations

Locations (1)

Department of Translational and Precision Medicine, Sapienza University of Rome, Umberto I Hospital; 🇮🇹 Rome, Italy