Pulmonary Arterial HypertensionNCT03905083
miRNA and Myokines in Patients With PAH
A study testing Exercise Rehab in people with Pulmonary Arterial Hypertension, run by University of Pittsburgh at 1 site in United States.
Trial summary
The overall objective of this study is to fulfill the Pilot study (miRNA and Myokines Acutely-expressed During Exercise) goal to Investigate the excretion of skeletal muscle-derived miRNA and myokines in patients with pulmonary arterial hypertension during acute exercise that are biologically active and modulate… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- Exercise Rehab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2021to 15 Jun 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- Patients undergoing a RHC/iCPET procedure at the UPMC Presbyterian Hospital Catheterization Lab.
- 18 years of age or older
- Able to read and understand the informed consent.
- Subjects who have signed the iCPET registry consent.
Who cannot join
- Pregnant women
- people under 18
- Who are unable to read and understand the informed consent.
- Subjects prescribed anticoagulant therapy
Trial locations and contacts
1 site in 1 country.
United States1 site
Division of Pulmonary, Allergy and Critical Care Medicine
Pittsburgh, Pennsylvania, 15213
About this study
Official title: miRNA and Myokines Acutely-expressed During Exercise in Patients With Pulmonary Arterial Hypertension
The overall objective of this study is to fulfill the Pilot study (miRNA and Myokines Acutely-expressed During Exercise) goal to Investigate the excretion of skeletal muscle-derived miRNA and myokines in patients with pulmonary arterial hypertension during acute exercise that are biologically active and modulate skeletal muscle function during exercise.
Pulmonary arterial hypertension (PAH), is characterized by the proliferation of endothelial and smooth muscle cells within the precapillary pulmonary vasculature, if untreated results in increased pulmonary vascular resistance and death. The hallmark perivascular infiltrates in PAH contain inflammatory macrophages and lymphocytes resulting in endothelial dysfunction and involves the dysregulation of distinct inflammatory mechanisms. Idiopathic PAH (iPAH) and scleroderma-associated PAH (SSc-PAH), are related by similar clinical and pathophysiologic features. Patients with PAH experience a central cardiovascular limitation to exercise. Despite effective treatment with pulmonary vasodilators, many resting PAH (rPAH) patients continue to experience exercise intolerance. PAH is increasingly acknowledged as a systemic disease, beyond abnormalities of the pulmonary vasculature. Although other contributions to exercise intolerance in PAH exist, skeletal muscle dysfunction significantly impacts exercise tolerance. The molecular mechanisms behind skeletal muscle dysfunction in PAH remain unclear. Provocative testing with invasive cardiopulmonary exercise testing challenges the cardio-pulmonary-vascular and skeletal muscle systems and elicits a cascade of physiologic events not measurable at rest. Myokines are circulating mediators released from skeletal muscle in an endocrine-like fashion in disease and health influencing many factors but not limited to systemic inflammation, immunity and endothelial function. Myokines have not been well described in PAH. Preliminary data indicate that myokines play important, yet still undescribed, roles in this disease. MicroRNAs (miRNAs) are small non-coding RNA molecules, which negatively regulate gene expression via repressing translation and degrading messenger RNAs through sequence-specific binding. There is a growing literature regarding the biological activity of extracellular miRNAs in PAH and in aerobic exercise. miR-126 has been implicated in skeletal muscle dysfunction in PAH, while miR-133 is skeletal muscle-specific but unlike miR-126 it is not yet implicated in skeletal muscle dysfunction in PAH.
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- Exercise Rehab
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exercise RehabOther
Participants who do the Exercise Rehab will engage in up to four center-based exercise rehab sessions each week for approximately 12 weeks; each session lasting roughly 1-hour with a stimulus (exercise) phase and a mix of warm up and cool down. Cycle ergometer and treadmill exercise may be used.
| Study group | Role | What they receive |
|---|---|---|
| Exercise rehab | Experimental | Investigators aim to evaluate how exercise training may provide beneficial effects on the skeletal muscle and/or pulmonary vasculature in select subjects with pulmonary arterial hypertension, scleroderma or mixed connective tissue disease or patients with exercise pulmonary arterial hypertension Receives: Other: Exercise Rehab |
| No exercsie rehab | No intervention | Some participants will not be assigned to do exercise rehab so we would be using them as a control arm to intervention group |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the impact of released miRNA/myokines on the skeletal muscle in PAH patients.
We will be able to measure the levels of miRNA by doing RNA sequencing and then To evaluate the impact of released miRNA/myokines on the skeletal muscle in PAH patients.Protein and transcript levels will be confirmed using Western blots and real-time PCR
Measured: At the time of the procedure
To evaluate the impact of formal exercise training on the skeletal muscle
Muscle biopsy for miRNA and myokine assessment will be performed for this outcome. Total RNA and protein extracted from quadriceps muscle biopsies will be used to measure RNA and protein expression. We will perform a secretome analysis utilizing the Mass Spectrometry Lab at the University of Pittsburgh for an unbiased assessment of muscle-secreted myokines in our subjects.
RNA sequencing and then Protein and transcript levels will be confirmed using Western blots and real-time PCR
Measured: At the time of the procedure
To evaluate the impact of formal exercise training on the pulmonary vasculature system
This will be done by measuring hemodynamics during invasive cardiopulmonary exercise test. We will correlate miRNA and myokines released from the skeletal muscle with measures of oxygen delivery and extraction in the muscle and oxygen consumption - calculated from arterial and pulmonary artery blood gasses and invasive hemodynamics. Oxygen delivery to peripheral tissues is determined by (Q ) ̇x CaO2. Oxygen extraction is Ca-vO2. Oxygen consumption is continuously measured by iCPET as( V) ̇O2. Systemic oxygen extraction ratio is determined by (Ca-vO2)/ CaO2
Measured: At the time of the procedure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2019
- Study startDec 2021 (estimated)
- Primary completion15 Mar 2023 (estimated)
- Study completion15 Jun 2023 (estimated)
Why it stopped: Logistics related to research activity
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe 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 N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael Risbano, University of Pittsburgh
- Investigators
- Michael Risbano, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03905083
- Sponsor's protocol ID
- STUDY19120032
- Status last verified
- Feb 2021
- First submitted
- 25 Feb 2019
- Last updated
- 3 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Our IPD plan would include: 1. The use of a controlled access approach, using a transparent and robust system to review requests and provide secure data access through asking data requester to fill up formal application that would give details on how this data would be used. 2. Seeking consent for sharing IPD from the clinical trial participants with adequate assurance that patient privacy and confidentiality can be maintained. 3. Establishing an approach to resource the sharing of IPD which would include support from trial funders, sponsor organizations and users of IPD.
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- miRNA and Myokines Acutely-expressed During Exercise in Patients With Pulmonary Arterial Hypertension
- ClinicalTrials.gov ID
- NCT03905083
- Acronym / sponsor ID
- STUDY19120032
- Conditions
- Pulmonary Arterial Hypertension
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Logistics related to research activity
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Study start
- Dec 2021 (estimated)
- Primary completion
- 15 Mar 2023 (estimated)
- Study completion
- 15 Jun 2023 (estimated)
- First posted
- 5 Apr 2019 (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 overall objective of this study is to fulfill the Pilot study (miRNA and Myokines Acutely-expressed During Exercise) goal to Investigate the excretion of skeletal muscle-derived miRNA and myokines in patients with pulmonary arterial hypertension during acute exercise that are biologically active and modulate skeletal muscle function during exercise.
Pulmonary arterial hypertension (PAH), is characterized by the proliferation of endothelial and smooth muscle cells within the precapillary pulmonary vasculature, if untreated results in increased pulmonary vascular resistance and death. The hallmark perivascular infiltrates in PAH contain inflammatory macrophages and lymphocytes resulting in endothelial dysfunction and involves the dysregulation of distinct inflammatory mechanisms. Idiopathic PAH (iPAH) and scleroderma-associated PAH (SSc-PAH), are related by similar clinical and pathophysiologic features. Patients with PAH experience a central cardiovascular limitation to exercise. Despite effective treatment with pulmonary vasodilators, many resting PAH (rPAH) patients continue to experience exercise intolerance. PAH is increasingly acknowledged as a systemic disease, beyond abnormalities of the pulmonary vasculature. Although other contributions to exercise intolerance in PAH exist, skeletal muscle dysfunction significantly impacts exercise tolerance. The molecular mechanisms behind skeletal muscle dysfunction in PAH remain unclear. Provocative testing with invasive cardiopulmonary exercise testing challenges the cardio-pulmonary-vascular and skeletal muscle systems and elicits a cascade of physiologic events not measurable at rest. Myokines are circulating mediators released from skeletal muscle in an endocrine-like fashion in disease and health influencing many factors but not limited to systemic inflammation, immunity and endothelial function. Myokines have not been well described in PAH. Preliminary data indicate that myokines play important, yet still undescribed, roles in this disease. MicroRNAs (miRNAs) are small non-coding RNA molecules, which negatively regulate gene expression via repressing translation and degrading messenger RNAs through sequence-specific binding. There is a growing literature regarding the biological activity of extracellular miRNAs in PAH and in aerobic exercise. miR-126 has been implicated in skeletal muscle dysfunction in PAH, while miR-133 is skeletal muscle-specific but unlike miR-126 it is not yet implicated in skeletal muscle dysfunction in PAH.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Exercise rehab | Experimental | Other: Exercise RehabInvestigators aim to evaluate how exercise training may provide beneficial effects on the skeletal muscle and/or pulmonary vasculature in select subjects with pulmonary arterial hypertension, scleroderma or mixed connective tissue disease or patients with exercise pulmonary arterial hypertension |
| No exercsie rehab | No intervention | –Some participants will not be assigned to do exercise rehab so we would be using them as a control arm to intervention group |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients undergoing a RHC/iCPET procedure at the UPMC Presbyterian Hospital Catheterization Lab.
- 18 years of age or older
- Able to read and understand the informed consent.
- Subjects who have signed the iCPET registry consent.
Key exclusion criteria (4 listed)
- Pregnant women
- people under 18
- Who are unable to read and understand the informed consent.
- Subjects prescribed anticoagulant therapy
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 |
|---|---|---|
| Exercise RehabParticipants who do the Exercise Rehab will engage in up to four center-based exercise rehab sessions each week for approximately 12 weeks; each session lasting roughly 1-hour with a stimulus (exercise) phase and a mix of warm up and cool down. Cycle ergometer and treadmill exercise may be used. | Other | Exercise rehab |
Primary outcome
To evaluate the impact of released miRNA/myokines on the skeletal muscle in PAH patients.
Time frame: At the time of the procedure
We will be able to measure the levels of miRNA by doing RNA sequencing and then To evaluate the impact of released miRNA/myokines on the skeletal muscle in PAH patients.Protein and transcript levels will be confirmed using Western blots and real-time PCR
To evaluate the impact of formal exercise training on the skeletal muscle
Time frame: At the time of the procedure
Muscle biopsy for miRNA and myokine assessment will be performed for this outcome. Total RNA and protein extracted from quadriceps muscle biopsies will be used to measure RNA and protein expression. We will perform a secretome analysis utilizing the Mass Spectrometry Lab at the University of Pittsburgh for an unbiased assessment of muscle-secreted myokines in our subjects. RNA sequencing and then Protein and transcript levels will be confirmed using Western blots and real-time PCR
To evaluate the impact of formal exercise training on the pulmonary vasculature system
Time frame: At the time of the procedure
This will be done by measuring hemodynamics during invasive cardiopulmonary exercise test. We will correlate miRNA and myokines released from the skeletal muscle with measures of oxygen delivery and extraction in the muscle and oxygen consumption - calculated from arterial and pulmonary artery blood gasses and invasive hemodynamics. Oxygen delivery to peripheral tissues is determined by (Q ) ̇x CaO2. Oxygen extraction is Ca-vO2. Oxygen consumption is continuously measured by iCPET as( V) ̇O2. Systemic oxygen extraction ratio is determined by (Ca-vO2)/ CaO2
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2022.
- Individual participant dataSharing planned: No. Our IPD plan would include: 1. The use of a controlled access approach, using a transparent and robust system to review requests and provide secure data access through asking data requester to fill up formal application that would give details on how this data would be used. 2. Seeking consent for sharing IPD from the clinical trial participants with adequate assurance that patient privacy and confidentiality can be maintained. 3. Establishing an approach to resource the sharing of IPD which would include support from trial funders, sponsor organizations and users of IPD.
Related trials for Pulmonary Arterial Hypertension
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A Pilot Study of Microbiota Transplant With Antibiotic Preconditioning and Fiber Supplementation in Pulmonary Arterial Hypertension (GUT RESTORE-PAH)
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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. This study is not recruiting at the moment.
Michael Risbano, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Exercise Rehab in people with Pulmonary Arterial Hypertension, run by University of Pittsburgh 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 4 inclusion and 4 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: withdrawn, as of the sponsor's last update on 3 Mar 2022. 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.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate the impact of released miRNA/myokines on the skeletal muscle in PAH patients. (time frame: At the time of the procedure). 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 3 Mar 2022.