Purpose


Category

IRB Number
20210284HU
NCT Number
NCT05305287
Sponsor
The University of Texas Health Science Center at San Antonio -



Study Contact

Principal Investigator
Luke Norton

Andrea Hansis-Diarte
210-567-3208
hansisdiarte@uthscsa.edu

Taylor Belinowski
210-450-1801
belinowski@uthscsa.edu



Eligibility

Eligible Ages
Between 18 Years and 75 Years
Eligible Genders
Male/Female
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 = 18-75 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 = 18-75 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)
Condition
  • Non-Alcoholic Fatty Liver Disease
  • Type 2 Diabetes
  • Mitochondrial Metabolism Disorders

    • Arm Groups

    ArmDescriptionIntervention
    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

    • 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

    NAFL Placebo

    		T2D with non-alcoholic fatty liver (NAFL), treated with placebo
  • Other: Placebo

    Placebo for pioglitazone

    • Placebo Comparator

    NASH Placebo

    		T2D with non-alcoholic steatohepatitis (NASH), treated with placebo
  • Other: Placebo

    Placebo for pioglitazone

    •