miRNA and Myokines in Patients With PAH

NCT ID: NCT03905083

Last Updated: 2022-03-03

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: NA
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-31
• Study Completion Date: 2023-06-15

Brief 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 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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Exercise rehab

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

Group Type: EXPERIMENTAL

Exercise Rehab

Intervention Type: OTHER

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.

No exercsie rehab

Some participants will not be assigned to do exercise rehab so we would be using them as a control arm to intervention group

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Exercise Rehab

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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• Pregnant women
• people under 18
• Who are unable to read and understand the informed consent.
• Subjects prescribed anticoagulant therapy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pittsburgh

OTHER

Sponsor Role: lead

Responsible Party

Michael Risbano

Head, Clinical Operations for Pulmonary Hypertension

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael Risbano, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

Division of Pulmonary, Allergy and Critical Care Medicine

Pittsburgh, Pennsylvania, United States

Countries

United States

Other Identifiers

STUDY19120032

Identifier Type: -

Identifier Source: org_study_id