Non-Alcoholic Fatty Liver DiseasePhase 4NCT05305287
Quantifying Hepatic Mitochondrial Fluxes in Humans
A Phase 4 study testing Pioglitazone in people with Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes, run by The University of Texas Health Science Center at San Antonio at 2 sites in United States.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Non-Alcoholic Fatty Liver Disease, Type 2 Diabetes, Mitochondrial Metabolism Disorders
- What is being tested?
- Pioglitazone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Nov 2022to 31 Mar 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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).
- 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 cannot join
- 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.
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- Urine albumin excretion > 300 mg/day.
- History of NY Class III-IV heart failure
- T2D with NASH
- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Texas Diabetes Institute - University Health System
San Antonio, Texas, 78207
Andrea Hansis-Diarte, MPh, 210-567-6691, hansisdiarte@uthscsa.edu
Luke Norton, PhD, 210-567-0739, hansisdiarte@uthscsa.edu
- Recruiting
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
About this study
Official title: Quantitation of Hepatic Mitochondrial Fluxes in Humans With Nonalcoholic Fatty Liver Disease (NAFLD)
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
Read the detailed description
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.
- Being tested
- Pioglitazone, Placebo
- Keywords
- NAFLD, Mitochondria, Type 2 diabetes, Insulin resistance
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Diabetes Mellitus, Type 2, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PioglitazoneDrug
Also called Actos
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.
PlaceboOther
Placebo for pioglitazone
| Study group | Role | What they receive |
|---|---|---|
| T2D + NAFL and pioglitazone | Experimental | Type 2 diabetes with non-alcoholic fatty liver (NAFL), treated with pioglitazone Receives: Drug: Pioglitazone |
| T2D + NAFL and placebo | Placebo comparator | Type 2 diabetes with non-alcoholic fatty liver (NAFL), treated with placebo Receives: Other: Placebo |
| T2D + NASH and pioglitazone | Experimental | Type 2 diabetes with non-alcoholic steatohepatitis (NASH), treated with pioglitazone Receives: Drug: Pioglitazone |
| T2D + NASH and placebo | Placebo comparator | Type 2 diabetes with non-alcoholic steatohepatitis (NASH), treated with placebo Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effect of pioglitazone on hepatic mitochondrial TCA cycle fluxes
Quantitated using a combined stable isotope approach before and after treatment with pioglitazone
Measured: Baseline, week 16
Secondary outcomes (8)
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
Measured: Baseline, Week 16
Effect of pioglitazone on the hepatic lipidome
Lipidomics will be carried out using mass-spectrometry methods
Measured: 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
Measured: Baseline, Week 16
Mean change from baseline in body weight
Mean change from baseline in body weight
Measured: Baseline, Week 16
Mean change from baseline in body composition
Mean change from baseline in lean and fat mass measured by DEXA
Measured: 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
Measured: 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)
Measured: 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
Measured: Week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2022
- Study start1 Nov 2022
- Primary completion31 Mar 2027 (estimated)
- Study completion31 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients with confirmed T2D will be screened for NAFL or NASH and will be randomly assigned to receive placebo or pioglitazone treatment groups.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The University of Texas Health Science Center at San Antonio
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Luke Norton, The University of Texas Health Science Center at San Antonio
- Investigators
- Luke Norton, PhD, Principal investigator, The University of Texas Health Science Center at San Antonio
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05305287
- Sponsor's protocol ID
- HSC20210284H
- Other IDs
- 1R01DK129676-01A1
- Status last verified
- Aug 2026
- First submitted
- 22 Mar 2022
- Last updated
- 17 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Quantitation of Hepatic Mitochondrial Fluxes in Humans With Nonalcoholic Fatty Liver Disease (NAFLD)
- ClinicalTrials.gov ID
- NCT05305287
- Acronym / sponsor ID
- HSC20210284H
- Keywords
- NAFLD, Mitochondria, Type 2 diabetes, Insulin resistance
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- The University of Texas Health Science Center at San AntonioUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 1 Nov 2022 (actual)
- Primary completion
- 31 Mar 2027 (estimated)
- Study completion
- 31 Mar 2027 (estimated)
- First posted
- 31 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 4
- Model description
- Patients with confirmed T2D will be screened for NAFL or NASH and will be randomly assigned to receive placebo or pioglitazone treatment groups.
| Arm | Type | Receives |
|---|---|---|
| T2D + NAFL and pioglitazone | Experimental | Drug: PioglitazoneType 2 diabetes with non-alcoholic fatty liver (NAFL), treated with pioglitazone |
| T2D + NAFL and placebo | Placebo comparator | Other: PlaceboType 2 diabetes with non-alcoholic fatty liver (NAFL), treated with placebo |
| T2D + NASH and pioglitazone | Experimental | Drug: PioglitazoneType 2 diabetes with non-alcoholic steatohepatitis (NASH), treated with pioglitazone |
| T2D + NASH and placebo | Placebo comparator | Other: PlaceboType 2 diabetes with non-alcoholic steatohepatitis (NASH), treated with placebo |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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;
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PioglitazoneAlso: ActosAn 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. | Drug | T2D + NAFL and pioglitazone, T2D + NASH and pioglitazone |
| PlaceboPlacebo for pioglitazone | Other | T2D + NAFL and placebo, T2D + NASH and placebo |
Primary outcome
Effect of pioglitazone on hepatic mitochondrial TCA cycle fluxes
Time frame: Baseline, week 16
Quantitated using a combined stable isotope approach before and after treatment with pioglitazone
8 secondary outcomes
Effect of pioglitazone on hepatic gene regulatory networks
Time frame: Baseline, Week 16
Effect of pioglitazone on the hepatic lipidome
Time frame: Baseline, Week 16
Mean absolute change from baseline in liver fat content by magnetic resonance Imaging - Proton Density Fat Fraction (MRI-PDFF)
Time frame: Baseline, Week 16
Mean change from baseline in body weight
Time frame: Baseline, Week 16
Mean change from baseline in body composition
Time frame: Baseline, Week 16
Quantitate the effect of pioglitazone on liver histology by improvement of fibrosis
Time frame: Week 16
Examine the effect of pioglitazone on non-invasive markers of NAFLD
Time frame: Baseline, Week 16
Quantitate the effect of pioglitazone on NAFLD Activity Score (NAS)
Time frame: Week 16
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Luke Norton, PhD principal investigator
The University of Texas Health Science Center at San Antonio
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Pioglitazone in people with Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes, run by The University of Texas Health Science Center at San Antonio at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Luke Norton, PhD (210-567-0739, nortonl@uthscsa.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effect of pioglitazone on hepatic mitochondrial TCA cycle fluxes (time frame: Baseline, week 16). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2026.