Measuring liver metabolism in patients with diabetes and fatty liver

Quantitation of Hepatic Mitochondrial Fluxes in Humans With Nonalcoholic Fatty Liver Disease (NAFLD)

This study is testing if a medication called pioglitazone can improve liver metabolism in people with type 2 diabetes and fatty liver disease over 16 weeks.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: The University of Texas Health Science Center at San Antonio (Academic / other)
• Locations: 2 sites (San Antonio, Texas and 1 other locations)
• Trial ID: NCT05305287 on ClinicalTrials.gov

What this trial studies

This study aims to quantify hepatic mitochondrial fluxes in patients with type 2 diabetes who have non-alcoholic fatty liver disease (NAFL) and non-alcoholic steatohepatitis (NASH). Participants will undergo a 16-week treatment with the insulin sensitizer pioglitazone, with assessments of liver metabolism conducted before and after the treatment. The study will utilize advanced techniques such as oral and intravenous isotopic tracers to evaluate mitochondrial function and insulin sensitivity, alongside liver biopsies for diagnostic purposes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-80 with type 2 diabetes and moderate to severe fatty liver without significant fibrosis.

Not a fit: Patients with cirrhosis, type 1 diabetes, or those consuming excessive alcohol may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved treatment strategies for patients with type 2 diabetes and fatty liver disease.

How similar studies have performed: Other studies have shown promising results with similar approaches in understanding liver metabolism and diabetes management.

Eligibility criteria

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.
* 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

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.
* 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

Where this trial is running

San Antonio, Texas and 1 other locations

• Texas Diabetes Institute - University Health System — San Antonio, Texas, United States (Recruiting)
• University of Texas Health Science Center at San Antonio — San Antonio, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Luke Norton, PhD — The University of Texas Health Science Center at San Antonio
• Study coordinator: Luke Norton, PhD

Conditions Non-Alcoholic Fatty Liver Disease; Type 2 Diabetes; Mitochondrial Metabolism Disorders; NAFLD; Diet; Exercise