Ignite Creation Date:
2024-05-06 @ 8:19 PM
Last Modification Date:
2024-10-26 @ 3:25 PM
Study NCT ID:
NCT06336798
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-06-26
First Post:
2024-03-22
Brief Title:
Bioenergetic Effect of Pioglitazone in CLD-PH
Sponsor:
Emory University
Organization:
Emory University
Study Overview
Official Title:
Effect of Pioglitazone on Mitochondrial Metabolism in Pulmonary Hypertension Due to Chronic Lung Disease
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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
Detailed Description:
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 US approximately 15 million US 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
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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| K23HL166775 | NIH | None | httpsreporternihgovquickSearchK23HL166775 |