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Pioglitazone on Heart Failure in Type-2 Diabetes Mellitus Participants (PIOHF)

Primary Purpose

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

Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Pioglitazone
Placebo
Sponsored by
The University of Texas Health Science Center at San Antonio
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 2 Diabetes Mellitus in Obese

Eligibility Criteria

30 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: 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. Exclusion Criteria: 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

Sites / Locations

  • Texas Diabetes Institute/UHRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Pioglitazone Administration Group

Placebo/Control Group

Arm Description

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

Placebo

Outcomes

Primary Outcome Measures

Change in Systolic function
Measurement of change in systolic function of the heart using cardiac MRI
Change in Diastolic function
Measurement of change in diastolic function of the heart using cardiac MRI

Secondary Outcome Measures

Myocardial insulin sensitivity
Measurement of change in Free Plasma Glucose (FPG) in blood plasma
Myocardial fat content
Measurement of change in myocardial fat content
PCr:ATP ratio
Measurement of change in PCr:ATP ratio

Full Information

First Posted
April 10, 2023
Last Updated
July 13, 2023
Sponsor
The University of Texas Health Science Center at San Antonio
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1. Study Identification

Unique Protocol Identification Number
NCT05838287
Brief Title
Pioglitazone on Heart Failure in Type-2 Diabetes Mellitus Participants
Acronym
PIOHF
Official Title
Pioglitazone, Lipotoxicity, and Heart Failure With Preserved Ejection Fraction (HFpEF)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 10, 2023 (Actual)
Primary Completion Date
April 2028 (Anticipated)
Study Completion Date
January 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The University of Texas Health Science Center at San Antonio

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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: 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. 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.
Detailed Description
Either Pioglitazone or Placebo Pioglitazone will be administered during this study in this Type 2 Diabetic population with Heart Failure to examine if there are any beneficial effects on diastolic and systolic function. Myocardial blood flow (MBF) is measured using a PET scan, then participants will be randomized to pioglitazone or a placebo to examine the effects of the study drug on the effects on the systolic and diastolic function of the heart. In addition, myocardial insulin sensitivity change will be measured as well as myocardial fat content. The ratio of ATP: PCr will also be measured.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes Mellitus in Obese, Heart Failure With Preserved Ejection Fraction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
double-blind placebo controlled, randomized clinical trial
Masking
ParticipantCare ProviderInvestigator
Masking Description
Neither the participant nor the investigator knows what treatment is given
Allocation
Randomized
Enrollment
78 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Pioglitazone Administration Group
Arm Type
Active Comparator
Arm Description
Pioglitazone 15mg/day titrated to 30 mg/day at week 2 and to 45 mg/day at week 4
Arm Title
Placebo/Control Group
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
Pioglitazone
Other Intervention Name(s)
Actos
Intervention Description
Participants will be taking Pioglitazone tablets 1/day for 24 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo tablet
Intervention Description
Placebo for Pioglitazone
Primary Outcome Measure Information:
Title
Change in Systolic function
Description
Measurement of change in systolic function of the heart using cardiac MRI
Time Frame
Baseline and 6-months post treatment (approximately 24 weeks)
Title
Change in Diastolic function
Description
Measurement of change in diastolic function of the heart using cardiac MRI
Time Frame
Baseline and 6-months post treatment (approximately 24 weeks)
Secondary Outcome Measure Information:
Title
Myocardial insulin sensitivity
Description
Measurement of change in Free Plasma Glucose (FPG) in blood plasma
Time Frame
Baseline and 6-months post treatment (approximately 24 weeks)
Title
Myocardial fat content
Description
Measurement of change in myocardial fat content
Time Frame
Baseline and 6-months post treatment (approximately 24 weeks)
Title
PCr:ATP ratio
Description
Measurement of change in PCr:ATP ratio
Time Frame
Baseline and 6-months post treatment (approximately 24 weeks)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sivaram Neppala, MD
Phone
210-358-7200
Email
neppalas@uthscsa.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Andrea Hansis-Diarte, MPH
Phone
210-567-3208
Email
Hansisdiarte@uthscsa.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ralph A DeFronzo, MD
Organizational Affiliation
University of Texas
Official's Role
Principal Investigator
Facility Information:
Facility Name
Texas Diabetes Institute/UH
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229-3900
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ralph DeFronzo, MD
Phone
210-358-7200
Email
defronzo@uthscsa.edu
First Name & Middle Initial & Last Name & Degree
Sivaram Neppala, MD
Phone
210-358-7200
Email
neppalas@uthscsa.edu
First Name & Middle Initial & Last Name & Degree
Ralph DeFronzo, MD
First Name & Middle Initial & Last Name & Degree
Sivaram Neppala, MD

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
IPD data will not be available to other researchers.

Learn more about this trial

Pioglitazone on Heart Failure in Type-2 Diabetes Mellitus Participants

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