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Quantifying Hepatic Mitochondrial Fluxes in Humans
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
ClinicalTrials.gov IDNCT05305287
PhasePHASE4
Enrollment60
SponsorThe University of Texas Health Science Center at San Antonio
Age18 Years
SexALL
Conditions studied
Non-Alcoholic Fatty Liver Disease, Type 2 Diabetes, Mitochondrial Metabolism Disorders
About this study
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
Interventions
- 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
Primary outcomes
- Effect of pioglitazone on hepatic mitochondrial TCA cycle fluxes (Baseline, week 16)
Eligibility information
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.
* Liver cirrhosis (fibrosis stage 4).
* 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.
* 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.
* 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.
* Liver cirrhosis (fibrosis stage 4).
* 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.
* 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.
* History of NY Class III-IV heart failure
Study locations
- Texas Diabetes Institute - University Health System, San Antonio, Texas 78207 United States
- University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229 United States
Before you participate: Varda Clinical is an independent discovery tool, not the study sponsor or a medical provider. Eligibility can only be determined by the official study team. Discuss potential risks and benefits with a qualified healthcare professional.
Source: ClinicalTrials.gov. Record last refreshed by Varda Clinical: 2026-09-27.