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Recruiting Phase 2

Low-Dose Pioglitazone in Patients With NASH (AIM 2)

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About this study

To determine the safety and efficacy of low-dose pioglitazone (15 mg per day) on liver histology in in patients with T2DM with biopsy-proven nonalcoholic steatohepatitis (NASH).

Condition
Type 2 Diabetes Mellitus (T2DM), Nonalcoholic Steatohepatitis
Tested
Pioglitazone, Placebo
Sponsor
University of Florida

Who can join

Age
21 to 75 years
Sex
All sexes
Healthy volunteers
Not accepted

Inclusion 11

  • Minimum age: 21 years
  • Maximum age: 75 years
  • Study condition: Type 2 Diabetes Mellitus (T2DM), Nonalcoholic Steatohepatitis
  • Able to communicate meaningfully with the investigator and legally competent to provide written informed consent.
  • Aged 21 to 75 years.
  • Patients with a diagnosis T2DM based on prior medical history, medication use, or results from a fasting plasma glucose or hemoglobin A1c, according to American Diabetes Association guidelines.
  • Patients will be allowed to participate the glycosylated hemoglobin (HbA1c) is ≤ 9.5% on diet alone or on a stable dose (for at least 2 months) of the following diabetes medications: metformin, sulfonylurea, acarbose, DPP-IV inhibitors, SGLT2 inhibitors or insulin.
  • The insulin total daily dose should be stable (defined as within 20% for the prior 2 months prior to study entry).
  • A GLP-1 receptor agonist will be allowed if on a stable dose for 6 months prior to enrollment and body weight stable (defined as within 3%) in the prior 3 months.
  • Diabetes medications will be continued at stable doses during the entire study (except if glycemic control deteriorates based on HbA1c; addition of metformin, sulfonylurea, acarbose, DPP-IV or insulin will be allowed if needed; pioglitazone, GLP-1RA or SGLT2 inhibitors will not).
  • Hemoglobin level of at least 11.0 g/L (men) or at least 10.0 g/L (women), leukocyte count of at least 3.0 × 109 cells/L, neutrophil count of at least 1.5 × 109 cells/L, platelet count of at least 100 × 109 cells/L, albumin level of at least 2.5 g/L, serum creatinine level of 2.5 mg/dL or less, INR \> 1.4, bilirubin \> 1.3 mg/dL (unless if non-conjugated bilirubin elevated in the setting of Gilbert's syndrome), and AST and ALT levels no more than 8 times the ULN.

Exclusion 23

  • Past or current history of alcohol use (\>20 g/d of ethanol in females or \>30g/d in males).
  • Alcohol abuse will be ruled out on the basis of physicians' judgment, self-reported alcohol use, and family members' report of the patient's alcohol use.
  • In addition, the Alcohol Use Disorders Identification Test (AUDIT) score will be used to assess alcohol use.
  • Receipt of long-term therapy with medications known to have adverse effects on glucose tolerance, unless the patient has been receiving a stable dose of such agents for 4 weeks before study entry.
  • Use of medications that could induce steatosis, such as estrogen or other hormonal replacement therapy, amiodarone, methotrexate, tamoxifen, raloxifene, pharmacological doses of oral glucocorticoids (≥10 mg per day of prednisone or equivalent), or chloroquine.
  • Use of vitamin E (doses ≥800 IU/dy) or pioglitazone or any FDA-approved drug for NASH to be approved during the study.
  • Any cause of chronic liver disease other than NASH, including but not restricted to alcohol or drug abuse, medication, chronic hepatitis B or C virus infection, autoimmune liver disease, hemochromatosis, Wilson disease (if younger than age 50), α1-antitrypsin deficiency, history of exposure to hepatotoxic drugs or history of primary or metastatic liver cancer.
  • Presence of other medical conditions known to cause fatty liver disease.
  • Any clinical or laboratory evidence of cirrhosis or hepatic decompensation, such as history of ascites, esophageal bleeding varices, or spontaneous encephalopathy.
  • Prior or scheduled surgical procedures, including gastroplasty or jejunoileal or jejunocolic bypass.
  • Prior exposure to organic solvents, such as carbon tetrachloride.
  • Total parenteral nutrition within the past 6 months.
  • Patients with other forms of diabetes other than T2DM.
  • History of clinically significant heart disease such as congestive heart failure (New York Heart Association Classification greater than grade II-IV), unstable cardiovascular disease such as unstable angina (i.e., new or worsening symptoms of coronary heart disease within the past 6 months), acute coronary syndrome or coronary artery intervention within the past 6 months, acute myocardial infarction in the past 6 months; history of (within prior 6 months) or current unstable cardiac dysrhythmias.
  • Uncontrolled hypertension (systolic blood pressure \>160 mmHg and/or diastolic blood pressure \>100 mmHg); clinically evident peripheral vascular disease (history of claudication); stroke or transient ischemic attack within the prior 6 months; clinically significant pulmonary disease (dyspnea on exertion of ≤1 flight; abnormal breath sounds on auscultation), or kidney disease as defined above per plasma creatinine elevation or significant proteinuria (macroalbuminuria).
  • Pregnancy or lactation in women.
  • Must have a negative pregnancy test or at least be two-year post-menopausal.
  • Women with childbearing potential (i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile) must be using a highly effective method of contraception (i.e. combined (estrogen and progesterone containing) hormonal/ progesterone-only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner).
  • The contraceptive method will have to be followed for at least one menstruation cycle after the end of the study.
  • History of malignancy in the past 5 years and/or active neoplasm with the exception of resolved superficial nonmelanoma skin cancer.
  • History of bladder disease and/or hematuria or has current hematuria unless due to a recent urinary tract infection.
  • Hemostasis disorders or current treatment with anticoagulants.
  • Any other criteria that based on the assessment of the research team the patient is deemed to be a poor research candidate.

Where

1 site, 1 recruiting

University of Florida

Gainesville, Florida, United States

Recruiting

Contact

Potential match only. Final eligibility is determined by the study team.