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

ConditionsType 2 Diabetes Mellitus (T2DM)Nonalcoholic Steatohepatitis

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age21-75

SponsorUniversity of Florida

About this trial

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).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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).

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

Pioglitazone
Drug
An insulin-sensitizer FDA-approved to treat hyperglycemia caused by type 2 diabetes.
Placebo
Other intervention
Placebo looks just like pioglitazone and is given in the same way but has no active drug in it.

Treatment groups

166 Participants

are divided into 2 treatment groups

Group A: PioglitazoneActive comparator 1 intervention

Group B: PlaceboPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

The proportion of pioglitazone-treated patients relative to placebo achieving an improvement of ≥2 points in non-alcoholic fatty liver disease activity score (NAS) without an increase in fibrosis stage.

The proportion of patients with liver histological improvement of ≥2 points in non-alcoholic fatty liver disease activity score (NAS) with a ≥1-point reduction in either ballooning or lobular inflammation and no increase in fibrosis stage by NASH CRN scoring criteria.

Time frame

72 weeks of treatment

Secondary outcomes

Resolution of NASH without worsening of liver fibrosis.

The proportion of pioglitazone-treated patients achieving NASH resolution, defined as hepatocellular ballooning score of 0 and lobular NASH CRN scoring criteria. inflammation score of 0-1, with no increase in fibrosis stage.

Time frame

72 weeks

Proportion of patients with improvement in the activity component of steatosis-activity-fibrosis (SAF) score.

Time frame

72 weeks.

Proportion of patients with NAS improvement (0-8).

The proportion of pioglitazone-treated patients achieving NAS improvement compared to placebo by NASH CRN scoring criteria.

Time frame

72 weeks.

Mean NAS change (0-8).

Defined as the mean change in the NAS score by NASH CRN scoring criteria.

Time frame

72 weeks.

Other outcomes

Liver fibrosis by imaging.

Measured by magnetic resonance elastography.

Time frame

72 weeks.

Intrahepatic triglyceride content

Measured by magnetic resonance imaging

Time frame

72 weeks.

CAP (controlled attenuation parameter) and vibration controlled transient elastography (VCTE)

Measurement of CAP and VCTE by Fibroscan.

Time frame

72 weeks.

Liver cT1 MRI mapping (Liver Multiscan)

A measurement of liver disease actvitiy

Time frame

72 weeks.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Florida

Lead sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Source ClinicalTrials.gov

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