RecruitingPhase 4NCT05305287

Quantifying Hepatic Mitochondrial Fluxes in Humans

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

Sponsor

The University of Texas Health Science Center at San Antonio

Enrollment

60 participants

Start Date

Nov 1, 2022

Study Type

INTERVENTIONAL

Conditions

Non-Alcoholic Fatty Liver Disease Type 2 Diabetes Mitochondrial Metabolism Disorders

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

Eligibility

Min Age: 18 YearsMax Age: 80 Years

Inclusion Criteria16

T2D with NAFL
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).
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 Criteria17

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
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

Interventions

DRUGPioglitazone

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.

OTHERPlacebo

Placebo for pioglitazone