Metabolic Associated Fatty Liver Disease with prediabetes.
Conditions
Interventions
Trade Name: metformin hydrochloride
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use
Trade Name: pioglitazone hydrochloride
Phar
Sponsors
Consorcio Centro de Investigación Biomédica en Red, M.P. (CIBER)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with HGADM according to the clinical criteria of the International Expert Consensus Statement. 2. Age from 18 to 75 years. 3. Men and postmenopausal women. 4. Evidence of significant nonalcoholic fatty liver disease, defined by a proportional attenuation of the intrahepatic signal> 10% observed by magnetic resonance imaging. 5. Overweight or obese with BMI 25-40 kg / m2 6. Presence of Prediabetes according to the ADA criteria (fasting blood glucose 100-125 mg / dl or HbA1c 5.7% -6.4% or blood glucose 140-199 mg / dl at 2 hours after SOG). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 293 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 97
Exclusion criteria
Exclusion criteria: 1. Patients with a life expectancy that is less than 5 years. 2. History of alcohol consumption> 30 g / day in men or> 20 g / day in women for 3 consecutive months in the last year. 3. Inability to maintain complete alcohol withdrawal during the study period. 4. Patients with decompensated liver cirrhosis or altered liver function (BiT> 2mg / dL, INR> 1.3). 5. Treatment with drugs potentially associated with fatty liver disease in the previous 3 months (amiodarone, corticosteroids, methotrexate, tetracyclines, tamoxifen, oral contraceptives). 6. History of hepatocarcinoma or malignancy in the 5 years prior to inclusion in the study, except cervical carcinoma in situ and basal cell carcinoma or cutaneous basal cell carcinoma. 7. Being undergoing chemotherapy or radiotherapy treatment. 8. Other causes of fatty liver: fasting, hemochromatosis, Wilson's disease, or autoimmune hepatitis. 9. Active evidence of HBV or HCV infection. 10. Severe heart failure; NYHA functional class III or IV. 11. Type 1 and 2 diabetes. 12. Taking other antidiabetic drugs. 13. Chronic diseases not related to metabolic disease: severe psychiatric, chronic kidney failure (GFR <45 ml / min), chronic respiratory failure, chronic processes necessary for treatment that can modify glucose metabolism. 14. Severe cardiovascular, renal, endocrine, gastrointestinal, or psychiatric comorbidity that, in the opinion of the investigator, may make adherence to treatment or interpretation of results difficult. 15. Participants in other clinical trials in the 30 days prior to the start of the study. 16. Sexually active men with a woman of childbearing age who plans to become pregnant. 17. Patients with limitation to follow the protocol for any reason.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine which of the three models of therapeutic intervention induces a greater sustained regression of fatty liver associated with long-term metabolic disease (18 months) measured by non-invasive techniques (MRI) in patients with Metabolic Associated Fatty Liver Disease and prediabetes.;Secondary Objective: • Investigate whether the variations of the genes involved consistently determine and / or condition the degree of response to dietary treatment with a hypocaloric Mediterranean diet and to drug treatment with metformin and pioglitazone. • Explore the changes induced by diet and each pharmacological treatment in the concentration of metabolites derived from mitochondrial function, intestinal microbiota. • To determine whether the changes in the concentration of alpha-ketoglutarate and other metabolites derived from the mitochondria induced by the therapeutic intervention models are associated with the progression or regression of fatty liver. • Establish which of the three models of therapeutic intervention induces an improvement in the pathogenic factors associated with the development of non-alcoholic fatty liver: peripheral insulin resistance, hepatic insulin resistance, adipose tissue dysfunction, intestinal microbiota.;Primary end point(s): Significant decrease in the amount of intrahepatic fat (> 20%) in the absence of liver fibrosis progression.;Timepoint(s) of evaluation of this end point: Baseline and at 18 months of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1. At Baseline, at 12 months and at 18 months of treatment. 2. Baseline and at 18 months of treatment. 3. Baseline and at 18 months of treatment. 4. Baseline. 5. Baseline, at 8 months and at 18 months. 6. From Baseline to 30 days after end of treatment, or study withdrawn.;Secondary end point(s): 1- Study of insulin resistance and adipose tissue dysfunction: 2- Search for non-invasive markers of efficacy of the proposed treatments among circulating metabolites (metabolomic and lipidomic methods). 3- Study of the intestinal microbiota. 4- Pharmacogenetic study: influence of genetic variations on the degree of therapeutic response to drugs. 5- Study of bioimpedanciometry. 6- Collection of adverse events potentially related to the medication and its administration. | — |
Countries
Spain
Contacts
Public ContactCIBER
Consorcio Centro de Investigación Biomédica en Red, M.P. (CIBER)
Outcome results
None listed