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

Obesity Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02951546
• Other study ID #: RIF.CE:4119
• Status: Completed
• Phase: N/A
• Start date: October 2016
• Est. completion date: February 2022

Study information

• Verified date: May 2022
• Source: University of Roma La Sapienza
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: February 2022
• Est. primary completion date: September 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non-alcoholic Fatty Liver Disease
• Obesity

Intervention

Dietary Supplement:
• Mediterranean diet
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
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.

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

Locations

Country	Name	City	State
Italy	Department of Translational and Precision Medicine, Sapienza University of Rome, Umberto I Hospital	Rome

Sponsors (4)

Lead Sponsor	Collaborator
University of Roma La Sapienza	Bambino Gesù Hospital and Research Institute, Göteborg University, Università degli studi di Roma Foro Italico

Country where clinical trial is conducted

Italy, 

Outcome

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