Non-alcoholic Fatty Liver DiseaseNCT02951546
Metabolic Flexibility, Gut Microbiota, Healthy Diet and Exercise in NAFLD on Genetics Base
A study testing Mediterranean diet, Low fat diet and Aerobic exercise in people with Non-alcoholic Fatty Liver Disease and Obesity, run by University of Roma La Sapienza at 1 site in Italy.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Non-alcoholic Fatty Liver Disease, Obesity
- What is being tested?
- Mediterranean diet, Low fat diet and Aerobic exercise
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteItaly
- Study dates
- Oct 2016to Feb 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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;
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Italy1 site
Department of Translational and Precision Medicine, Sapienza University of Rome, Umberto I Hospital
Rome, 00185
About this study
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
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.
Read more
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.
Read the 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.
- Conditions
- Non-alcoholic Fatty Liver Disease, Obesity
- Being tested
- Mediterranean diet, Low fat diet, Aerobic exercise
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mediterranean dietDietary 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 dietDietary 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 exerciseOther
A personalized program of aerobic exercise will be prescribed to the participants of both arms, following the "FITT" principles (frequency, intensity, time and type).
| Study group | Role | What they receive |
|---|---|---|
| Mediterranean diet | Experimental | Hypocaloric Mediterranean diet for a 4-month period;
Aerobic exercise training for a 4-month period; Receives: 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; Receives: Dietary Supplement: Low fat diet; Other: Aerobic exercise |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cholesterol assessment
total cholesterol, HDL- cholesterol, LDL- cholesterol levels reported as mg/dl
Measured: baseline
Cholesterol assessment
total cholesterol, HDL- cholesterol, LDL- cholesterol levels reported as mg/dl
Measured: 18 weeks after baseline
triglycerides assessment
tryglicerides levels reported as mg/dl
Measured: baseline
triglycerides assessment
tryglicerides levels reported as mg/dl
Measured: 18 weeks after baseline
metabolic flexibility variation in liver function;
alanine aminotransferase (ALT) [U/L] , aspartate aminotransferase (AST) [UI/L]
Measured: baseline
metabolic flexibility variation in liver function;
alanine aminotransferase (ALT) [U/L] , aspartate aminotransferase (AST) [UI/L]
Measured: 18 weeks after baseline
Waist circumference measurements;
waist circumference reported as cm
Measured: baseline
Waist circumference measurements;
waist circumference reported as cm
Measured: 18 weeks after baseline
anthropometric measurements;
Body mass index reported as kg/m^2
Measured: baseline
anthropometric measurements;
Body mass index reported as kg/m^2
Measured: 18 weeks after baseline
Ultrasonographic examination;
Liver ultrasonography according with criteria by Hamaguchi
Measured: baseline
Ultrasonographic examination;
Liver ultrasonography according with criteria by Hamaguchi
Measured: 18 weeks after baseline
Glucidic profile
fasting glucose reported as mg/dl
Measured: baseline
Glucidic profile
fasting glucose reported as mg/dl
Measured: 18 weeks after baseline
Insulinemia
insulin reported as µU/mL
Measured: baseline
Insulinemia
insulin reported as µU/mL
Measured: 18 weeks after baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2016 (estimated)
- Study startOct 2016
- Primary completionSep 2021
- Study completionFeb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- More trials run by University of Roma La SapienzaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- None (open label)
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Roma La Sapienza
- Sponsor type
- University, hospital or other
- Collaborators
- Bambino Gesù Hospital and Research Institute, Università degli studi di Roma Foro Italico, Göteborg University
- Responsible party
- Principal investigator, STEFANO GINANNI CORRADINI, University of Roma La Sapienza
- Investigators
- Stefano Ginanni Corradini, MD, PhD, Principal investigator, Department Translational and Precision Medicine, Sapienza University of Rome
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02951546
- Sponsor's protocol ID
- RIF.CE:4119
- Status last verified
- May 2022
- First submitted
- 26 Oct 2016
- Last updated
- 27 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02951546
- Acronym / sponsor ID
- RIF.CE:4119
- Conditions
- Non-alcoholic Fatty Liver Disease, Obesity
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- University of Roma La SapienzaUniversity, hospital or other
- Collaborators
- Bambino Gesù Hospital and Research Institute, Università degli studi di Roma Foro Italico, Göteborg University
- Study start
- Oct 2016 (actual)
- Primary completion
- Sep 2021 (actual)
- Study completion
- Feb 2022 (actual)
- First posted
- 1 Nov 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Mediterranean diet | Experimental | Dietary Supplement: Mediterranean diet, Other: Aerobic exerciseHypocaloric Mediterranean diet for a 4-month period; Aerobic exercise training for a 4-month period; |
| Low fat diet | Experimental | Dietary Supplement: Low fat diet, Other: Aerobic exerciseHypocaloric 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; |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (14 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mediterranean dietIn 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. | Dietary supplement | Mediterranean diet |
| Low fat dietIn 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. | Dietary supplement | Low fat diet |
| Aerobic exerciseA personalized program of aerobic exercise will be prescribed to the participants of both arms, following the "FITT" principles (frequency, intensity, time and type). | Other | Low fat diet, Mediterranean diet |
Primary outcome
Cholesterol assessment
Time frame: baseline
total cholesterol, HDL- cholesterol, LDL- cholesterol levels reported as mg/dl
Cholesterol assessment
Time frame: 18 weeks after baseline
total cholesterol, HDL- cholesterol, LDL- cholesterol levels reported as mg/dl
triglycerides assessment
Time frame: baseline
tryglicerides levels reported as mg/dl
triglycerides assessment
Time frame: 18 weeks after baseline
tryglicerides levels reported as mg/dl
metabolic flexibility variation in liver function;
Time frame: baseline
alanine aminotransferase (ALT) [U/L] , aspartate aminotransferase (AST) [UI/L]
metabolic flexibility variation in liver function;
Time frame: 18 weeks after baseline
alanine aminotransferase (ALT) [U/L] , aspartate aminotransferase (AST) [UI/L]
Waist circumference measurements;
Time frame: baseline
waist circumference reported as cm
Waist circumference measurements;
Time frame: 18 weeks after baseline
waist circumference reported as cm
anthropometric measurements;
Time frame: baseline
Body mass index reported as kg/m^2
anthropometric measurements;
Time frame: 18 weeks after baseline
Body mass index reported as kg/m^2
Ultrasonographic examination;
Time frame: baseline
Liver ultrasonography according with criteria by Hamaguchi
Ultrasonographic examination;
Time frame: 18 weeks after baseline
Liver ultrasonography according with criteria by Hamaguchi
Glucidic profile
Time frame: baseline
fasting glucose reported as mg/dl
Glucidic profile
Time frame: 18 weeks after baseline
fasting glucose reported as mg/dl
Insulinemia
Time frame: baseline
insulin reported as µU/mL
Insulinemia
Time frame: 18 weeks after baseline
insulin reported as µU/mL
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 May 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stefano Ginanni Corradini, MD, PhD principal investigator
Department Translational and Precision Medicine, Sapienza University of Rome
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Mediterranean diet, Low fat diet and Aerobic exercise in people with Non-alcoholic Fatty Liver Disease and Obesity, run by University of Roma La Sapienza at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cholesterol assessment (time frame: baseline). The study lists 16 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 May 2022.