A Phase 4 interventional study of Pioglitazone and Placebo in Non-Alcoholic Fatty Liver Disease, Type 2 Diabetes and Mitochondrial Metabolism Disorders, sponsored by The University of Texas Health Science Center at San Antonio. Recruiting at 2 sites in United States. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2026-08-17.
Sponsored by The University of Texas Health Science Center at San Antonio · Phase 4, Interventional, and Basic science
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
The study team will examine hepatic mitochondrial TCA flux and pyruvate cycling (oral [U-13C]-propionate), hepatic gluconeogenesis (oral 2H2O), and hepatic insulin sensitivity (intravenous [3,4-13C2]-glucose with euglycemic insulin clamp) before and after 16 weeks treatment with the FDA approved insulin sensitizer pioglitazone. These studies will be performed in (i) type 2 diabetic subjects with NAFL but without evidence of fibrosis, and (ii) type 2 diabetic patients with NASH. Liver biopsies will be obtained before and after treatment for the diagnosis of NAFL/NASH and for molecular analyses.
1,474 studies on the registry are indexed under Non-alcoholic Fatty Liver Disease; 303 are open to participants now.
This study's planned enrollment of 60 is close to the median of 60 across 1,072 interventional studies indexed under Non-alcoholic Fatty Liver Disease.
Browse Non-alcoholic Fatty Liver Disease studies →The University of Texas Health Science Center at San Antonio is the lead sponsor of 435 studies on the registry; 88 are open to participants now.
Of its 62 completed or terminated interventional studies of FDA-regulated products, 31 (50%) have results posted.
Counted across the registry records on this site, refreshed daily.
T2D with NAFL
Inclusion Criteria:
Exclusion Criteria:
T2D with NASH
Inclusion Criteria:
Exclusion Criteria:
Type 2 diabetes with non-alcoholic fatty liver (NAFL), treated with pioglitazone
Drug: Pioglitazone
Type 2 diabetes with non-alcoholic fatty liver (NAFL), treated with placebo
Other: Placebo
Type 2 diabetes with non-alcoholic steatohepatitis (NASH), treated with pioglitazone
Drug: Pioglitazone
Type 2 diabetes with non-alcoholic steatohepatitis (NASH), treated with placebo
Other: Placebo
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
Placebo for pioglitazone
Effect of pioglitazone on hepatic mitochondrial TCA cycle fluxes
Quantitated using a combined stable isotope approach before and after treatment with pioglitazone
Time frame: Baseline, week 16
Effect of pioglitazone on hepatic gene regulatory networks
Multimodal RNA-Seq and ATAC-Seq will be used to examine gene regulatory networks in liver samples
Time frame: Baseline, Week 16
Effect of pioglitazone on the hepatic lipidome
Lipidomics will be carried out using mass-spectrometry methods
Time frame: Baseline, Week 16
Mean absolute change from baseline in liver fat content by magnetic resonance Imaging - Proton Density Fat Fraction (MRI-PDFF)
Mean absolute change from baseline in liver fat content by MRI-PDFF
Time frame: Baseline, Week 16
Mean change from baseline in body weight
Mean change from baseline in body weight
Time frame: Baseline, Week 16
Mean change from baseline in body composition
Mean change from baseline in lean and fat mass measured by DEXA
Time frame: Baseline, Week 16
Quantitate the effect of pioglitazone on liver histology by improvement of fibrosis
Percentage of Participants with ≥1 Point Decrease in Fibrosis Stage with No Worsening of NASH on Liver Histology
Time frame: Week 16
Examine the effect of pioglitazone on non-invasive markers of NAFLD
Mean change from baseline in Fibrosis-4 (FIB-4), transient elastography (Fibroscan®), NAFLD fibrosis score (NFS), alanine transaminase (ALT) and aspartate transaminase (AST)
Time frame: Baseline, Week 16
Quantitate the effect of pioglitazone on NAFLD Activity Score (NAS)
Percentage of Participants that Achieve a ≥2 Point Decrease in NAS on Liver Histology, with ≥1 Point Reduction in at Least 2 NAS Components
Time frame: Week 16
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Non-alcoholic Fatty Liver Disease→
The University of Texas Health Science Center at San Antonio