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Bioenergetic Effect of Pioglitazone in CLD-PH

Study Purpose

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).

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

 No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

 Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Provision of 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; Diagnosis must be confirmed by right heart catheterization.
Right heart catheterization must be within 1 year of screening.
  • - 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 prior to arrival for the study visit.

Exclusion Criteria:

  • - 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.
  • - New York Heart Association Class III or IV symptoms due to heart failure at enrollment.
  • - 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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

 NCT06336798
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

 Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

 Emory University
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

 Aaron Trammell
Principal Investigator Affiliation Emory University
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

 Other, NIH
Overall Status Not yet recruiting
Countries
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

 Pulmonary Hypertension, Pulmonary Hypertension Due to Lung Diseases
Additional Details

Pulmonary hypertension (PH) is a state of chronic elevated pressure in the pulmonary circulation. PH has multiple possible causes, clinically classified into 5 separate groups according to the World Symposium on PH classification scheme. PH is common in adults, with increasing prevalence with age, and is associated with significant symptom burden and mortality. In the U.S., approximately 1.5 million U.S. adults have PH, including 5-10% of people >65. Metabolic abnormalities have been highlighted recently as contributing to PH pathogenesis, disease severity, and outcome. In pre-clinical studies, reduced mitochondrial metabolism (oxidative phosphorylation) and reliance on alternative metabolic pathways (glycolysis) have been shown to promote pulmonary vascular remodeling and PH. Mechanistic investigation has shown that reduced PPARγ activity in lung vascular cells is necessary and sufficient to cause cellular proliferation and dysfunction followed by PH, all of which can be reversed by available pharmacotherapies designed to activate PPARγ. Metabolic changes have been demonstrated in 1) lung vessels from multiple PH animal models and 2) humans with PAH 3) right ventricle from humans with PAH, 4) skeletal muscle from humans with PAH, 5) circulating platelets from humans with PAH and PH due to left heart disease. Clinical trials of therapies that activate PPARγ have not been previously conducted in patients with PH but are believed by experts in the field to be a highly promising therapeutic approach. In this trial, the investigators will study the mitochondrial metabolic effects ("bioenergetics") of pioglitazone, an available medication from the class of thiazolidinedione (TZD) drugs that activate PPARγ. This medication is FDA-approved for the treatment of Type II diabetes mellitus (DM). Pioglitazone has been studied in non-diabetics with diverse other conditions demonstrating safety. The study team will assess cellular energy metabolism through a sophisticated assay of bioenergetics. The investigators and others have shown that bioenergetics can be measured in isolated platelets obtained from a peripheral blood draw in patients with PH and other diseases. Furthermore, others have shown that in PAH, platelet bioenergetics correlate with known disease-relevant metabolic changes in lung blood vessels. In this study, the team will assess the effect of pioglitazone on bioenergetic parameters in platelets isolated from whole blood samples.

Arms & Interventions

Arms

Experimental: Pioglitazone, Then Placebo

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.

Experimental: Placebo, Then Pioglitazone

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.

Interventions

Drug: - Pioglitazone 30mg

Study participants will take Pioglitazone 30 mg PO daily

Drug: - Placebo

Study participants will take a placebo PO daily

Diagnostic Test: - Labs

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

Contact Information

This trial has no sites locations listed at this time. If you are interested in learning more, you can contact the trial's primary contact:

Aaron Trammell, MD, MSc

awtramm@emory.edu

404-712-8204

For additional contact information, you can also visit the trial on clinicaltrials.gov.

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