Pulmonary HypertensionPhase 2NCT06336798
Bioenergetic Effect of Pioglitazone in CLD-PH
A Phase 2 study testing Pioglitazone 30mg and Labs in people with Pulmonary Hypertension and Pulmonary Hypertension Due to Lung Diseases, run by Emory University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Hypertension, Pulmonary Hypertension Due to Lung Diseases
- What is being tested?
- Pioglitazone 30mg and Labs
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Dec 2024to Feb 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
Show all 13Show fewer
- 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 locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Emory Healthcare System
Atlanta, Georgia, 30322
Jane Gillespie, RN, 404-712-8204, jegille@emory.edu
Aaron W Trammell, MD, MSc
About this study
Official title: Effect of Pioglitazone on Mitochondrial Metabolism in Pulmonary Hypertension Due to Chronic Lung Disease
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).
Read the 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 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.
- Being tested
- Pioglitazone 30mg, Placebo, Labs
- Keywords
- Pulmonary Hypertension, Chronic Lung Disease, Pioglitazone
- Medical subject headings
- Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pioglitazone 30mgDrug
Also called Actos
Study participants will take Pioglitazone 30 mg PO daily
PlaceboDrug
Study participants will take a placebo PO daily
LabsDiagnostic test
Also called Diagnostic labs
Labs will be performed for Urine HCG, Complete Blood count (CBC), Chemistry Panel, Fasting lipids, insulin, glucose, and Bioenergetic analysis (platelets).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Pioglitazone 30mg; Drug: Placebo; Diagnostic Test: Labs |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Day 1, Day 28, Day 70
Secondary outcomes (8)
Number of hypoglycemia incidences
Participants experiencing symptoms of hypoglycemia will be identified and reported.
Measured: Day 1, Day 28, Day 70
Number of participants with leg edema
Participants reporting edema (>2) will be captured.
Measured: Day 1, Day 28, Day 70
Change in BNP levels
Change in Brain Natriuretic Peptide from the baseline will be calculated. Unit is pg/ml
Measured: Day 1, Day 28, Day 70
Change in Six minute walk distance (6MWT)
The six-minute walk test (6MWT) is a standardized test of exercise capacity commonly used in patients with heart failure, lung disease, PH, and in pre-lung transplant evaluation. Results will be recorded as the distance walked in meters.
Measured: Day 1, Day 28, Day 70
Change in Borg dyspnea score
Borg dyspnea score assessed before and after 6MWT. The Borg dyspnea score is a rating of dyspnea that is scored between 0 and 10. Higher scores indicate worse dyspnea.
Measured: Day 1, Day 28, Day 70
Change in NYHA/WHO Functional Classification
The New York Heart Association / World Health Organization Functional Classification (NYHA/WHO FC) is a symptom-based score graded on a scale from I-IV. It is used to objectively assess severity of symptoms for patients with heart failure, PH, and other cardiopulmonary conditions. In this study, NYHA/WHO FC will be recorded at each study visit. Higher scores indicate a higher degree of functional limitation.
Measured: Day 1, Day 28, Day 70
Change in University of California San Diego Shortness of Breath Questionnaire score
The University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ) is a 24-item measure that assesses self-reported shortness of breath while performing a variety of activities of daily living. It is self-completed by participants and is validated in multiple languages (including US English) and in diseases including COPD, ILD, and general states of dyspnea. Each of the 24 items is scored on a six-point scale (0-5). Total scores range from 0 to 120 with higher scores indicating worse dyspnea.
Measured: Day 1, Day 28, Day 70
Change in emPHasis-10 Questionnaire score
The emPHasis-10 questionnaire consists of 10 items that address breathlessness, fatigue, control, and confidence and is designed to assess the impacts that PH has on a person's quality of life. Each of the items is scored on a six-point scale (0-5). emPHasis-10 scores range from 0 to 50 with higher scores indicating worse quality of life.
Measured: Day 1, Day 28, Day 70
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2024
- Study start17 Dec 2024
- Primary completionFeb 2028 (estimated)
- Study completionFeb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary HypertensionStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Aaron W Trammell, Emory University
- Investigators
- Aaron Trammell, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06336798
- Sponsor's protocol ID
- STUDY00005871
- Other IDs
- K23HL166775, 2025P010116
- Status last verified
- Jul 2026
- First submitted
- 22 Mar 2024
- Last updated
- 22 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Pioglitazone on Mitochondrial Metabolism in Pulmonary Hypertension Due to Chronic Lung Disease
- ClinicalTrials.gov ID
- NCT06336798
- Acronym / sponsor ID
- STUDY00005871
- Keywords
- Pulmonary Hypertension, Chronic Lung Disease, Pioglitazone
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 17 Dec 2024 (actual)
- Primary completion
- Feb 2028 (estimated)
- Study completion
- Feb 2028 (estimated)
- First posted
- 29 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pioglitazone, Then Placebo | Experimental | Drug: Pioglitazone 30mg, Drug: Placebo, Diagnostic Test: LabsParticipants 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. |
| Placebo, Then Pioglitazone | Experimental | Drug: Pioglitazone 30mg, Drug: Placebo, Diagnostic Test: LabsParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
- 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
Key exclusion criteria (13 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pioglitazone 30mgAlso: ActosStudy participants will take Pioglitazone 30 mg PO daily | Drug | Pioglitazone, Then Placebo, Placebo, Then Pioglitazone |
| PlaceboStudy participants will take a placebo PO daily | Drug | Pioglitazone, Then Placebo, Placebo, Then Pioglitazone |
| LabsAlso: Diagnostic labsLabs will be performed for Urine HCG, Complete Blood count (CBC), Chemistry Panel, Fasting lipids, insulin, glucose, and Bioenergetic analysis (platelets). | Diagnostic test | Pioglitazone, Then Placebo, Placebo, Then Pioglitazone |
Primary outcome
Change in Mitochondrial metabolism parameters: Spare respiratory capacity
Time frame: Day 1, Day 28, Day 70
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.
Change in Mitochondrial metabolism parameters: Maximal respiration
Time frame: Day 1, Day 28, Day 70
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.
Change in Mitochondrial metabolism parameters: Basal respiration
Time frame: Day 1, Day 28, Day 70
Basal respiration is calculated by (Baseline) - (nonmitochondrial respiration) ) during the mitochondrial stress test. The value is reported in pmol/min.
8 secondary outcomes
Number of hypoglycemia incidences
Time frame: Day 1, Day 28, Day 70
Number of participants with leg edema
Time frame: Day 1, Day 28, Day 70
Change in BNP levels
Time frame: Day 1, Day 28, Day 70
Change in Six minute walk distance (6MWT)
Time frame: Day 1, Day 28, Day 70
Change in Borg dyspnea score
Time frame: Day 1, Day 28, Day 70
Change in NYHA/WHO Functional Classification
Time frame: Day 1, Day 28, Day 70
Change in University of California San Diego Shortness of Breath Questionnaire score
Time frame: Day 1, Day 28, Day 70
Change in emPHasis-10 Questionnaire score
Time frame: Day 1, Day 28, Day 70
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Aaron Trammell principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pioglitazone 30mg and Labs in people with Pulmonary Hypertension and Pulmonary Hypertension Due to Lung Diseases, run by Emory University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Aaron Trammell, MD, MSc (404-712-8204, awtramm@emory.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Mitochondrial metabolism parameters: Spare respiratory capacity (time frame: Day 1, Day 28, Day 70). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2026.