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Purpose

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

Eligibility

Eligible Ages
Between 18 Years and 80 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 4
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Patients with T2D and NAFL or NASH will be randomly assigned to receive placebo or pioglitazone treatment groups.
Primary Purpose
Basic Science
Masking
Single (Participant)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
NAFL TZD 		T2D with non-alcoholic fatty liver (NAFL), treated with pioglitazone
  • Drug: Pioglitazone
    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.
    Other names:
    • Actos
Placebo Comparator
NAFL Placebo 		T2D with non-alcoholic fatty liver (NAFL), treated with placebo
  • Other: Placebo
    Placebo for pioglitazone
Experimental
NASH TZD 		T2D with non-alcoholic steatohepatitis (NASH), treated with pioglitazone
  • Drug: Pioglitazone
    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.
    Other names:
    • Actos
Placebo Comparator
NASH Placebo 		T2D with non-alcoholic steatohepatitis (NASH), treated with placebo
  • Other: Placebo
    Placebo for pioglitazone

Recruiting Locations

Texas Diabetes Institute - University Health System
San Antonio, Texas 78207
Contact:
Andrea Hansis-Diarte, MPh
210-567-6691
hansisdiarte@uthscsa.edu

More Details

Status
Recruiting
Sponsor
The University of Texas Health Science Center at San Antonio

Study Contact

Luke Norton, PhD
210-567-0739
nortonl@uthscsa.edu

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.