RECRUITING

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

Conditions

Type 2 Diabetes Mellitus (T2DM)Nonalcoholic Steatohepatitis Nonalcoholic fatty liver disease; pioglitazone.

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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).

Official Title

Effect of Low-Dose Pioglitazone in Patients With Nonalcoholic Steatohepatitis (NASH)

Quick Facts

Study Start:2020-12-15

Study Completion:2027-08-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04501406

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:21 Years to 75 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Able to communicate meaningfully with the investigator and legally competent to provide written informed consent. 2. Aged 21 to 75 years. 3. 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. 4. 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). 5. 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.	1. 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. 2. 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. 3. 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. 4. Use of vitamin E (doses ≥800 IU/dy) or pioglitazone or any FDA-approved drug for NASH to be approved during the study. 5. 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. 6. Presence of other medical conditions known to cause fatty liver disease. 7. Any clinical or laboratory evidence of cirrhosis or hepatic decompensation, such as history of ascites, esophageal bleeding varices, or spontaneous encephalopathy. 8. Prior or scheduled surgical procedures, including gastroplasty or jejunoileal or jejunocolic bypass. 9. Prior exposure to organic solvents, such as carbon tetrachloride. 10. Total parenteral nutrition within the past 6 months. 11. Patients with other forms of diabetes other than T2DM. 12. 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. 13. 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). 14. 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. 15. History of malignancy in the past 5 years and/or active neoplasm with the exception of resolved superficial nonmelanoma skin cancer. 16. History of bladder disease and/or hematuria or has current hematuria unless due to a recent urinary tract infection. 17. Hemostasis disorders or current treatment with anticoagulants. 18. Any other criteria that based on the assessment of the research team the patient is deemed to be a poor research candidate.

Inclusion Criteria

Exclusion Criteria

1. Able to communicate meaningfully with the investigator and legally competent to provide written informed consent.
2. Aged 21 to 75 years.
3. 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.
4. 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).
5. 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.

1. 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.
2. 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.
3. 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.
4. Use of vitamin E (doses ≥800 IU/dy) or pioglitazone or any FDA-approved drug for NASH to be approved during the study.
5. 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.
6. Presence of other medical conditions known to cause fatty liver disease.
7. Any clinical or laboratory evidence of cirrhosis or hepatic decompensation, such as history of ascites, esophageal bleeding varices, or spontaneous encephalopathy.
8. Prior or scheduled surgical procedures, including gastroplasty or jejunoileal or jejunocolic bypass.
9. Prior exposure to organic solvents, such as carbon tetrachloride.
10. Total parenteral nutrition within the past 6 months.
11. Patients with other forms of diabetes other than T2DM.
12. 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.
13. 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).
14. 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.
15. History of malignancy in the past 5 years and/or active neoplasm with the exception of resolved superficial nonmelanoma skin cancer.
16. History of bladder disease and/or hematuria or has current hematuria unless due to a recent urinary tract infection.
17. Hemostasis disorders or current treatment with anticoagulants.
18. Any other criteria that based on the assessment of the research team the patient is deemed to be a poor research candidate.

Contacts and Locations

Study Contact

Kenneth Cusi, M.D.

CONTACT

3522738662

kcusi@ufl.edu

Principal Investigator

Kenneth Cusi, MD

PRINCIPAL_INVESTIGATOR

University of Florida

Study Locations (Sites)

University of Florida

Gainesville, Florida, 32610

United States

Collaborators and Investigators

Sponsor: University of Florida

Kenneth Cusi, MD, PRINCIPAL_INVESTIGATOR, University of Florida

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-12-15

Study Completion Date2027-08-31

Study Record Updates

Study Start Date2020-12-15

Study Completion Date2027-08-31

Terms related to this study

Keywords Provided by Researchers

Nonalcoholic fatty liver disease; pioglitazone.

Additional Relevant MeSH Terms

Type 2 Diabetes Mellitus (T2DM)
Nonalcoholic Steatohepatitis