Bioenergetic Effect of Pioglitazone in CLD-PH

NCT06336798 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: STUDY00005871K23HL166775
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn about the safety and efficacy of Pioglitazone in people with Pulmonary Hypertension (PH) due to Chronic Lung Disease (CLD). The main question it aims to answer is: • Whether pioglitazone affects mitochondrial oxygen utilization in patients with PH due to CLD. Participants will be asked to take pioglitazone or placebo once daily for 28 days followed by a washout period of 2 weeks followed by 28 days of the other study drug (participants randomized to placebo followed by pioglitazone or pioglitazone followed by placebo).

Conditions

Pulmonary Hypertension; Pulmonary Hypertension Due to Lung Diseases

Keywords

Pulmonary Hypertension; Chronic Lung Disease; Pioglitazone

Outcome Measures

Primary Outcomes (3)

• Change in Mitochondrial metabolism parameters: Spare respiratory capacity

  Mitochondrial metabolism is measured using a research protocol employing the Agilent Seahorse extracellular flux bioanalyzer. Standard Seahorse assay protocols have been adapted for use with human platelets . Spare respiratory capacity (SRC) is calculated by (maximal respiration) - (basal respiration) during the mitochondrial stress test. The value is reported in pmol/min.

  Day 1, Day 28, Day 70

• Change in Mitochondrial metabolism parameters: Maximal respiration

  Maximal Respiration is calculated by: (post-carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone(FCCP) - (nonmitochondrial respiration) during the mitochondrial stress test. The value is reported in pmol/min.

  Day 1, Day 28, Day 70

• Change in Mitochondrial metabolism parameters: Basal respiration

  Basal respiration is calculated by (Baseline) - (nonmitochondrial respiration) ) during the mitochondrial stress test. The value is reported in pmol/min.

  Day 1, Day 28, Day 70

Secondary Outcomes (8)

• Number of hypoglycemia incidences

  Day 1, Day 28, Day 70

• Number of participants with leg edema

  Day 1, Day 28, Day 70

• Change in BNP levels

  Day 1, Day 28, Day 70

• Change in Six minute walk distance (6MWT)

  Day 1, Day 28, Day 70

• Change in Borg dyspnea score

  Day 1, Day 28, Day 70

Study Arms (2)

Pioglitazone, Then Placebo

EXPERIMENTAL

Participants will first receive a 30 mg tablet of Pioglitazone once daily for 28 days. After a washout period of 14 days, they will then receive a Placebo tablet (matching Pioglitazone 30 mg tablet) once daily for 28 days.

Drug: Pioglitazone 30mg; Drug: Placebo; Diagnostic Test: Labs

Placebo, Then Pioglitazone

EXPERIMENTAL

Participants will first receive a Placebo for 28 days. After a washout period of 14 days, they will then receive a 30 mg Pioglitazone tablet once daily for 28 days.

Drug: Pioglitazone 30mg; Drug: Placebo; Diagnostic Test: Labs

Interventions

Pioglitazone 30mg DRUG

Study participants will take Pioglitazone 30 mg PO daily

Also known as: Actos

Pioglitazone, Then Placebo; Placebo, Then Pioglitazone

Placebo DRUG

Study participants will take a placebo PO daily

Pioglitazone, Then Placebo; Placebo, Then Pioglitazone

Labs DIAGNOSTIC_TEST

Labs will be performed for Urine HCG, Complete Blood count (CBC), Chemistry Panel, Fasting lipids, insulin, glucose, and Bioenergetic analysis (platelets).

Also known as: Diagnostic labs

Pioglitazone, Then Placebo; Placebo, Then Pioglitazone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of a signed and dated informed consent form
• Stated willingness to comply with all study procedures for the duration of the study
• Confirmed to have pulmonary hypertension (PH) due to chronic lung disease at screening
• Pulmonary hypertension is defined based on meeting all three of the following measured at rest during the RHC:
• Mean pulmonary artery pressure \>20 mmHg
• Pulmonary artery wedge pressure ≤15 mmHg
• Pulmonary vascular resistance \> 2 Wood units
• Pulmonary hypertension is classified in Group 3: PH associated with lung diseases and/or hypoxia
• Medications approved for the treatment of pulmonary hypertension must be at a stable dose for at least 30 days
• Ability to take oral medication and be willing to adhere to the study intervention regimen
• For females of reproductive potential: agreement to use highly effective contraception 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 a partner
• Agreement to adhere to Lifestyle Considerations (below) throughout the study duration o During this study, participants are asked to arrive in the clinic for study visits in the fasting state. Specifically, participants should abstain from any caloric intake for 6 hours before arrival for the study visit.

You may not qualify if:

• Diabetes mellitus (type 1 or type 2), present within the preceding 1 year
• Personal history of symptomatic hypoglycemia within 90 days preceding enrollment
• Personal outpatient use of pioglitazone, rosiglitazone, metformin, insulin, or other medications for the indication of diabetes within 90 days preceding enrollment
• History of left ventricular failure (systolic or diastolic)
• Pulmonary hypertension due to Group 2 PH (PH due to left heart disease)
• History of prior or active bladder cancer
• Thrombocytopenia (diagnosis or known platelet count ≤120) within 90 days preceding enrollment
• Platelet count ≤120 during screening or on the day of enrollment hypertension due to chronic lung disease
• Cystic fibrosis
• Pregnancy or lactation
• Current tobacco use
• Known allergic reaction to components of the study medication (pioglitazone)
• Treatment with another investigational drug within 30 days

Sponsors & Collaborators

• Emory University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Emory Healthcare System

Atlanta, Georgia, 30322, United States

RECRUITING

MeSH Terms

Conditions

Hypertension, Pulmonary

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Aaron Trammell

  Emory University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aaron Trammell, MD, MSc

CONTACT

404-712-8204; awtramm@emory.edu

Jane Gillespie, RN

CONTACT

404-712-8204; jegille@emory.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 22, 2024
• First Posted: March 29, 2024
• Study Start: December 17, 2024
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028
• Last Updated: July 3, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)