Recruiting

Observational Study

Sponsor:

The University of Texas Health Science Center at San Antonio

Code:

NCT05305287

Conditions

Non-Alcoholic Fatty Liver Disease

Type 2 Diabetes

Mitochondrial Metabolism Disorders

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Pioglitazone

Placebo

Study Details

Brief summary:

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

Conditions

Non-Alcoholic Fatty Liver Disease

Type 2 Diabetes

Mitochondrial Metabolism Disorders

Study ID

NCT05305287

Start date

Nov 1, 2022

Status verified date

Aug, 2026

Completion date

Mar 31, 2027

Anticipated

Primary completion date

Mar 31, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

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 Design

Enrollment

60 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: T2D + NAFL and pioglitazone

Type 2 diabetes with non-alcoholic fatty liver (NAFL), treated with pioglitazone

placebo comparator: T2D + NAFL and placebo

Type 2 diabetes with non-alcoholic fatty liver (NAFL), treated with placebo

experimental: T2D + NASH and pioglitazone

Type 2 diabetes with non-alcoholic steatohepatitis (NASH), treated with pioglitazone

placebo comparator: T2D + NASH and placebo

Type 2 diabetes with non-alcoholic steatohepatitis (NASH), treated with placebo

Interventions

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.

Placebo

Placebo for pioglitazone

Primary outcome measure

  • Effect of pioglitazone on hepatic mitochondrial TCA cycle fluxes [ Time Frame: Baseline, week 16 ]

Central Contacts and Locations

Central contacts

Luke Norton, PhD

210-567-0739nortonl@uthscsa.edu

Andrea Hansis-Diarte, MPH

210-567-3208hansisdiarte@uthscs.edu

Locations

Texas Diabetes Institute - University Health System

Recruiting

San Antonio, Texas, United States, 78207

Contacts

Andrea Hansis-Diarte, MPh

210-567-6691hansisdiarte@uthscsa.edu

Luke Norton, PhD

210-567-0739hansisdiarte@uthscsa.edu

University of Texas Health Science Center at San Antonio

Recruiting

San Antonio, Texas, United States, 78229

More Information

Sponsor

The University of Texas Health Science Center at San Antonio

Last update posted

Aug 17, 2026

Last verified

Aug, 2026

Keywords

  • NAFLD
  • Mitochondria
  • Type 2 diabetes
  • Insulin resistance

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by The University of Texas Health Science Center at San Antonio on 2026-08-17.