RECRUITINGPhase 4INTERVENTIONAL
Quantifying Hepatic Mitochondrial Fluxes in Humans
Quantitation of Hepatic Mitochondrial Fluxes in Humans With Nonalcoholic Fatty Liver Disease (NAFLD)
About This Trial
In this study the investigators will quantitate hepatic mitochondrial fluxes in T2D patients with NAFL and NASH before and after 16-weeks treatment with the insulin sensitizer pioglitazone
Who May Be Eligible (Plain English)
T2D with NAFL
Who May Qualify:
- Confirmed T2D based on OGTT (2 h glucose ≥200 mg/dl).
- Treated with diet, metformin, and/or sulfonylurea and in good general health determined by medical history, physical exam, and routine blood chemistries;
- age = 18-80 years;
- BMI = 25-40 kg/m2;
- HbA1c = 7-10%; stable body weight (±4 pounds) over the preceding 3-months;
- not taking any medication known to affect glucose metabolism other than antidiabetic medications.
- Evidence of moderate/severe fatty liver (steatosis; grade S2/S3 on FibroScan corresponding to ≥10% fat on MRI-PDFF) and no/minimal hepatic fibrosis (grade F0/F1 on FibroScan).
Who Should NOT Join This Trial:
- Alcohol consumption \>14 units/week for women and \>21 units/week for men.
- Cirrhosis (fibrosis stage 4).
- Type 1 diabetes and/or GAD positive subjects.
- Subjects not drug naive or have been on metformin more than 3 months.
- Presence of proliferative retinopathy.
- Urine albumin excretion \> 300 mg/day.
- Evidence of other forms of chronic liver disease, including alcoholic liver disease, hepatitis B and C, primary biliary cholangitis, suspected/proven liver cancer and any other liver disease other than NAFLD.
- History of NY Class III-IV heart failure
T2D with NASH
Who May Qualify:
- Confirmed T2D based on OGTT (2 h glucose ≥200 mg/dl).
- Treated with diet, metformin, and/or sulfonylurea and in good general health determined by medical history, physical exam, and routine blood chemistries;
- age = 18-80 years;
- BMI = 25-40 kg/m2;
- HbA1c = 7-10%;
- stable body weight (±4 pounds) over the preceding 3-months;
- not taking any medication known to affect glucose metabolism other than antidiabetic medications.
- Evidence of moderate/severe fatty liver (steatosis; grade S2/S3 on FibroScan corresponding to ≥10% liver fat on MRI-PDFF) and moderate/severe hepatic fibrosis (grade F2/F3 on FibroScan).
Who Should NOT Join This Trial:
...See full criteria on ClinicalTrials.gov
Always talk to your doctor about whether this trial is right for you.
Original Eligibility Criteria
View original clinical language
T2D with NAFL
Inclusion Criteria:
* Confirmed T2D based on OGTT (2 h glucose ≥200 mg/dl).
* Treated with diet, metformin, and/or sulfonylurea and in good general health determined by medical history, physical exam, and routine blood chemistries;
* age = 18-80 years;
* BMI = 25-40 kg/m2;
* HbA1c = 7-10%; stable body weight (±4 pounds) over the preceding 3-months;
* not taking any medication known to affect glucose metabolism other than antidiabetic medications.
* Evidence of moderate/severe fatty liver (steatosis; grade S2/S3 on FibroScan corresponding to ≥10% fat on MRI-PDFF) and no/minimal hepatic fibrosis (grade F0/F1 on FibroScan).
Exclusion Criteria:
* Alcohol consumption \>14 units/week for women and \>21 units/week for men.
* Cirrhosis (fibrosis stage 4).
* Type 1 diabetes and/or GAD positive subjects.
* Subjects not drug naive or have been on metformin more than 3 months.
* Presence of proliferative retinopathy.
* Urine albumin excretion \> 300 mg/day.
* Evidence of other forms of chronic liver disease, including alcoholic liver disease, hepatitis B and C, primary biliary cholangitis, suspected/proven liver cancer and any other liver disease other than NAFLD.
* History of NY Class III-IV heart failure
T2D with NASH
Inclusion Criteria:
* Confirmed T2D based on OGTT (2 h glucose ≥200 mg/dl).
* Treated with diet, metformin, and/or sulfonylurea and in good general health determined by medical history, physical exam, and routine blood chemistries;
* age = 18-80 years;
* BMI = 25-40 kg/m2;
* HbA1c = 7-10%;
* stable body weight (±4 pounds) over the preceding 3-months;
* not taking any medication known to affect glucose metabolism other than antidiabetic medications.
* Evidence of moderate/severe fatty liver (steatosis; grade S2/S3 on FibroScan corresponding to ≥10% liver fat on MRI-PDFF) and moderate/severe hepatic fibrosis (grade F2/F3 on FibroScan).
Exclusion Criteria:
* Alcohol consumption \>14 units/week for women and \>21 units/week for men.
* Cirrhosis (fibrosis stage 4).
* Type 1 diabetes and/or GAD positive subjects.
* Subjects not drug naive or have been on metformin more than 3 months.
* Presence of proliferative retinopathy.
* Urine albumin excretion \> 300 mg/day.
* Evidence of other forms of chronic liver disease, including alcoholic liver disease, hepatitis B and C, primary biliary cholangitis, suspected/proven liver cancer and any other liver disease other than NAFLD.
* History of NY Class III-IV heart failure
Treatments Being Tested
DRUG
Pioglitazone
An insulin sensitizer and anti-diabetic agent. Participants will be started on 15 mg/day, increased to 30 mg/day at week 2 and then to 45 mg/day at week 4.
OTHER
Placebo
Placebo for pioglitazone
Locations (2)
Texas Diabetes Institute - University Health System
San Antonio, Texas, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States