Clinical trial NCT02951546: Metabolic Flexibility, Gut Microbiota, Healthy Diet and Exercise in NAFLD on Genetics Base
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Non-alcoholic Fatty Liver Disease
Obesity
Lead sponsor: University of Roma La Sapienza
Sponsor class: OTHER
Collaborators: name: Bambino Gesù Hospital and Research Institute
name: Università degli studi di Roma Foro Italico
name: Göteborg University
First posted: 2016-11-01
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Cholesterol assessment
timeFrame: baseline
measure: Cholesterol assessment
timeFrame: 18 weeks after baseline
measure: triglycerides assessment
timeFrame: baseline
measure: triglycerides assessment
timeFrame: 18 weeks after baseline
measure: metabolic flexibility variation in liver function;
timeFrame: baseline
measure: metabolic flexibility variation in liver function;
timeFrame: 18 weeks after baseline
measure: Waist circumference measurements;
timeFrame: baseline
measure: Waist circumference measurements;
timeFrame: 18 weeks after baseline
measure: anthropometric measurements;
timeFrame: baseline
measure: anthropometric measurements;
timeFrame: 18 weeks after baseline
measure: Ultrasonographic examination;
timeFrame: baseline
measure: Ultrasonographic examination;
timeFrame: 18 weeks after baseline
measure: Glucidic profile
timeFrame: baseline
measure: Glucidic profile
timeFrame: 18 weeks after baseline
measure: Insulinemia
timeFrame: baseline
measure: Insulinemia
timeFrame: 18 weeks after baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Department of Translational and Precision Medicine, Sapienza University of Rome, Umberto I Hospital
Study officials:
affiliation: Department Translational and Precision Medicine, Sapienza University of Rome
name: Stefano Ginanni Corradini, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: