Quantifying Hepatic Mitochondrial Fluxes in Humans

NCT05305287 | Recruiting Phase 4 FDA Drug

• 2 other identifiers: HSC20210284H1R01DK129676-01A1
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

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

Keywords

NAFLD; Diet; Exercise

Outcome Measures

Primary Outcomes (1)

• Effect of pioglitazone on hepatic mitochondrial TCA cycle fluxes

  Quantitated using a combine stable isotope approach before and after treatment with pioglitazone

  Baseline, week 16

Secondary Outcomes (8)

• Mean absolute change from baseline in liver fat content by magnetic resonance Imaging - Proton Density Fat Fraction (MRI-PDFF)

  Baseline, Week 16

• Mean change from baseline in body weight

  Baseline, Week 16

• Mean change from baseline in body composition

  Baseline, Week 16

• Quantitate the effect of pioglitazone on liver histology by improvement of fibrosis

  Week 16

• Quantitate the effect of pioglitazone on NAFLD Activity Score (NAS)

  Week 16

Study Arms (4)

NAFL TZD

EXPERIMENTAL

T2D with non-alcoholic fatty liver (NAFL), treated with pioglitazone

Drug: Pioglitazone

NAFL Placebo

PLACEBO COMPARATOR

T2D with non-alcoholic fatty liver (NAFL), treated with placebo

Other: Placebo

NASH TZD

EXPERIMENTAL

T2D with non-alcoholic steatohepatitis (NASH), treated with pioglitazone

Drug: Pioglitazone

NASH Placebo

PLACEBO COMPARATOR

T2D with non-alcoholic steatohepatitis (NASH), treated with placebo

Other: Placebo

Interventions

Pioglitazone DRUG

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.

Also known as: Actos

NAFL TZD; NASH TZD

Placebo OTHER

Placebo for pioglitazone

NAFL Placebo; NASH Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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
• 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;

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• The University of Texas Health Science Center at San Antonio: lead

Study Sites (2)

Texas Diabetes Institute - University Health System

San Antonio, Texas, 78207, United States

RECRUITING

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Diabetes Mellitus, Type 2; Motor Activity

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Behavior

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Luke Norton, PhD

  The University of Texas Health Science Center at San Antonio

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Luke Norton, PhD

CONTACT

210-567-0739; nortonl@uthscsa.edu

Andrea Hansis-Diarte, MPH

CONTACT

210-567-3208; hansisdiarte@uthscs.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Patients with T2D and NAFL or NASH will be randomly assigned to receive placebo or pioglitazone treatment groups.

Study Record Dates

• First Submitted: March 22, 2022
• First Posted: March 31, 2022
• Study Start: November 1, 2022
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027
• Last Updated: January 9, 2026

Record last verified: 2026-01

Locations

US (2)