What side effects are associated with this type of intervention?

Thiazolidinediones, such as pioglitazone, are commonly used to treat NAFLD by improving insulin sensitivity and reducing inflammation. However, they are associated with several side effects, including weight gain, fluid retention, and an increased risk of heart failure. Additionally, there is a potential for bone fractures, particularly in women. Metformin, another treatment option, can cause gastrointestinal issues like nausea and diarrhea. GLP-1 receptor agonists, which are also used to manage NAFLD, may lead to gastrointestinal side effects such as nausea, vomiting, and diarrhea. It is important for patients to discuss these potential side effects with their healthcare provider to determine the most appropriate treatment plan.

What prior FDA approvals exist?

As of now, there are no FDA-approved medications specifically for the treatment of Non-alcoholic Fatty Liver Disease (NAFLD). However, Pioglitazone, a PPAR-gamma agonist, has been studied for its potential benefits in improving insulin sensitivity and reducing inflammation in patients with NAFLD. Other drugs under investigation include vitamin E and various GLP-1 receptor agonists, which have shown promise in clinical trials but have not yet received FDA approval for this specific indication.

What other types of research exist?

Promising alternatives to Pioglitazone for NAFLD patients include GLP-1 receptor agonists (such as liraglutide), metformin, and potentially other emerging therapies targeting insulin sensitivity and inflammation. These options have shown efficacy in improving liver histology and metabolic parameters in NAFLD patients.

← Back to Search

Thiazolidinedione

Low-Dose Pioglitazone for NASH

Phase 2

Recruiting

Led By Kenneth Cusi, MD

Research Sponsored by University of Florida

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Aged 21 to 75 years

Patients with glycosylated hemoglobin (HbA1c) ≤ 9.5% on diet alone or on a stable dose of specified diabetes medications

Must not have

Patients with other forms of diabetes other than T2DM

Uncontrolled hypertension, clinically evident peripheral vascular disease, stroke or transient ischemic attack within the prior 6 months, clinically significant pulmonary disease, or kidney disease as defined above per plasma creatinine elevation or significant proteinuria

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 72 weeks

Awards & highlights

All Individual Drugs Already Approved

Summary

This trial is testing a small daily dose of pioglitazone in patients with type 2 diabetes and a specific liver condition called NASH. The goal is to see if this medication can improve their liver health by helping their bodies manage blood sugar and fat levels better.

Who is the study for?

This trial is for adults aged 21-75 with Type 2 Diabetes and biopsy-proven nonalcoholic steatohepatitis (NASH). Participants must have certain blood cell counts, liver function tests within specific limits, controlled diabetes (HbA1c ≤ 9.5%), and not be on medications affecting glucose tolerance or have other liver diseases. Pregnant women, heavy alcohol users, those with recent malignancies or heart disease are excluded.

What is being tested?

The study aims to test the safety and effectiveness of a low-dose pioglitazone treatment (15 mg daily) compared to a placebo in improving liver health for patients with NASH who also have Type 2 Diabetes. The participants will either receive the actual medication or a placebo without knowing which one they are taking.

What are the potential side effects?

Pioglitazone may cause fluid retention leading to swelling and weight gain, increase risk of bone fractures especially in women, and could potentially worsen diabetic eye disease. It's also linked to bladder cancer risk when used long-term at higher doses.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I am between 21 and 75 years old.

Select...

My HbA1c level is 9.5% or lower, and I manage it with diet or stable diabetes medication.

Select...

I have been diagnosed with Type 2 Diabetes.

Select...

I can understand and communicate about the study, and I can legally consent.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have a form of diabetes that is not type 2.

Select...

I do not have uncontrolled high blood pressure, recent strokes, severe lung or kidney disease.

Select...

My chronic liver disease is not due to NASH.

Select...

I have a medical condition that causes fatty liver disease.

Select...

I have been exposed to chemicals like carbon tetrachloride.

Select...

I have been on IV nutrition in the last 6 months.

Select...

I have had or am scheduled for weight loss surgery.

Select...

I do not have signs of severe liver disease or cirrhosis.

Select...

I consume more than the recommended amount of alcohol daily.

Select...

I have a history of serious heart problems.

Select...

I have a bleeding disorder or am currently on blood thinners.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 72 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~72 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 72 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

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.

Secondary study objectives

Fibrosis improvement.

Improvement of fibrosis AND resolution of NASH as a composite endpoint.

Improvement of fibrosis by at least 2 stages.

+9 more

Other study objectives

Adipose tissue insulin sensitivity (Adipo-IR)

Atlas imaging

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

+7 more

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Trial Design

2Treatment groups

Active Control

Placebo Group

Group I: PioglitazoneActive Control1 Intervention

Two arm, randomized, double-blind, placebo-controlled, 72 week treatment study receiving pioglitazone 15mg/day.

Group II: PlaceboPlacebo Group1 Intervention

Two arm, randomized, double-blind, placebo-controlled, 72 week treatment study receiving placebo.

0 / 15Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Non-alcoholic Fatty Liver Disease (NAFLD) include PPAR-gamma agonists like Pioglitazone, which improve insulin sensitivity and reduce inflammation. These drugs activate peroxisome proliferator-activated receptor gamma (PPAR-gamma), leading to enhanced glucose metabolism and decreased fatty acid synthesis in the liver. This results in reduced hepatic steatosis and inflammation, which are key factors in the progression of NAFLD. Other treatments, such as GLP-1 agonists and SGLT2 inhibitors, also improve metabolic parameters and reduce liver fat. These mechanisms are important for NAFLD patients as they address the underlying metabolic dysfunction and help prevent the progression to more severe liver disease.