Pioglitazone on Heart Failure in Type-2 Diabetes Mellitus Participants

NCT05838287 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: HSC20220916H
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

Our goal of the study is to learn the effects of the diabetes medication named Pioglitazone, in type-2 diabetic obese participants with Heart failure. The main question it aims to answer are:

1. 1.To demonstrate that impaired mitochondrial function leading to reduced ATP generation plays a key pathophysiologic role in the development of heart failure with preserved ejection fraction (HFpEF) in obese type 2 diabetic (T2D) individuals.
2. 2.To demonstrate that pioglitazone, improves diastolic (as well as systolic) function by improving myocardial insulin sensitivity and by reducing both myocardial and epicardial fat content.

Conditions

Type 2 Diabetes Mellitus in Obese; Heart Failure With Preserved Ejection Fraction

Outcome Measures

Primary Outcomes (2)

• Change in Systolic function

  Measurement of change in systolic function of the heart using cardiac MRI

  Baseline and 6-months post treatment (approximately 24 weeks)

• Change in Diastolic function

  Measurement of change in diastolic function of the heart using cardiac MRI

  Baseline and 6-months post treatment (approximately 24 weeks)

Secondary Outcomes (3)

• Myocardial insulin sensitivity

  Baseline and 6-months post treatment (approximately 24 weeks)

• Myocardial fat content

  Baseline and 6-months post treatment (approximately 24 weeks)

• PCr:ATP ratio

  Baseline and 6-months post treatment (approximately 24 weeks)

Study Arms (2)

Pioglitazone Administration Group

ACTIVE COMPARATOR

Pioglitazone 15mg/day titrated to 30 mg/day at week 2 and to 45 mg/day at week 4

Drug: Pioglitazone

Placebo/Control Group

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Pioglitazone DRUG

Participants will be taking Pioglitazone tablets 1/day for 24 weeks.

Also known as: Actos

Pioglitazone Administration Group

Placebo DRUG

Placebo for Pioglitazone

Also known as: Placebo tablet

Placebo/Control Group

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged 30-70 years
• Body Mass Index (BMI) of 27.5-40kg/m²
• HbA1c of 6.5 to 10%
• Blood pressure of less than or equal to 145/65mmHg
• eGFR greater than 45 ml/min/1.73m²
• Subject must have HFpEF (EF \> 50% by ECHO screening)
• NYHA class II-III heart failure
• Only T2D patients treated with diet/exercise, metformin, sulfonylurea, metformin/SU, DPP4i or insulin will be studied.
• For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional \[4 weeks\] after the end of study participation.
• For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner.

You may not qualify if:

• Subjects with history of osteoporosis or proliferative diabetic retinopathy
• Subjects with Heart failure due to restrictive or infiltrative cardiomyopathy, active myocarditis, constrictive pericarditis, severe valvular heart disease, etc. will be excluded
• Patients with symptomatic coronary artery disease.
• Subjects with significant change in diuretic management during the month prior to screening (defined by doubling of diuretic dose, or addition of another HF medication).
• Subjects treated with a GLP-1 RA or thiazolidinedione.
• Subjects treated with a SGLT2i
• Pregnancy or lactation
• Known allergic reactions to components of the study interventions.
• Any metal plates, parts, screws, shrapnel, pins in body, or cardiac (heart) pacemaker

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead

Study Sites (1)

Texas Diabetes Institute/UH

San Antonio, Texas, 78229-3900, United States

RECRUITING

MeSH Terms

Interventions

Pioglitazone

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Ralph A DeFronzo, MD

  University of Texas

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sivaram Neppala, MD

CONTACT

210-358-7200; neppalas@uthscsa.edu

Andrea Hansis-Diarte, MPH

CONTACT

210-567-3208; Hansisdiarte@uthscsa.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Neither the participant nor the investigator knows what treatment is given
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: double-blind placebo controlled, randomized clinical trial

Study Record Dates

• First Submitted: April 10, 2023
• First Posted: May 1, 2023
• Study Start: July 10, 2023
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): January 1, 2030
• Last Updated: August 27, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)