NCT04501406

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

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 166 (estimated)
• Sponsor: University of Florida · Academic / Other
• Sex: All
• Age: 21 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

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).

Detailed description

Rationale: Several studies have shown that pioglitazone, at either 30 to 45 mg per day, is safe and effective in randomized, controlled trials (RCTs) of 6- to 24-month duration (Belfort et al, NEJM 2006; Aithal et al, Gastroenterology 2008; Sanyal et al, NEJM 2010; Cusi et al, Annals Int Med 2016; Bril et al, Diabetes Care 2019). However, pioglitazone has shown to also improve glucose and lipid metabolism at the lower dose of 15 mg per day in patients with type 2 diabetes (Aronoff et al, Diabetes Care 2000; Miyazaki et al, Diabetes Care 2002; Rosenstock et al, Int J Clin Pract. 2002; Rajagopalan et al, Diabetes Res Clin Pract 2015). However, the effect of pioglitazone at doses of 15 mg per day on liver histology in patients with steatohepatitis (NASH) has not been previously examined. Study aim: To examine the safety and efficacy of "low-dose" (15 mg/day) pioglitazone compared to placebo (control) in patients with type 2 diabetes and NASH in a 72-week randomized controlled study design. Description: This is a single center, phase 2A, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of pioglitazone in subjects that are 21 to 75 years of age, with nonalcoholic steatohepatitis (NASH) confirmed by liver biopsy and who have type 2 diabetes. Eligible subjects will be enrolled into two treatments arms: Pioglitazone 15 mg or placebo in a ratio 1:1. All subjects will be enrolled and followed at the our research center, the University of Florida NIH-sponsored Clinical Translational Science Institute. Upon study entry, patients will undergo a detailed medical history, physical exam, baseline routine laboratories, EKG, elastography (VCTE). Those who meet al inclusion/exclusion criteria will undergo further imaging by MRI and measurement of blood diagnostic panels hormones and biomarkers relevant to the disease state (steatohepatitis). A liver biopsy, if not done prior to study entry, will be performed. Patients that qualify (NASH with fibrosis F1-F3) will be randomized in a double-blind fashion to either pioglitazone or placebo. They will be followed during 10 scheduled visits after randomization for 72 weeks of treatment. Blood testing, imaging and a liver biopsy will be repeated as done at baseline. After completion of the study treatment period, subjects will be followed for an additional period of 4 weeks without study medication (week 76).

Conditions

• Type 2 Diabetes Mellitus (T2DM)
• Nonalcoholic Steatohepatitis

Interventions

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

Timeline

• Start date: 2020-12-15
• Primary completion: 2027-08-31
• Completion: 2027-08-31
• First posted: 2020-08-06
• Last updated: 2025-04-04

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study