Clinical trial NCT03905083: miRNA and Myokines in Patients With PAH
Official title: miRNA and Myokines Acutely-expressed During Exercise in Patients With Pulmonary Arterial Hypertension
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Pulmonary Arterial Hypertension
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
First posted: 2019-04-05
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.


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

Primary outcomes:
measure: To evaluate the impact of released miRNA/myokines on the skeletal muscle in PAH patients.
timeFrame: At the time of the procedure
measure: To evaluate the impact of formal exercise training on the skeletal muscle
timeFrame: At the time of the procedure
measure: To evaluate the impact of formal exercise training on the pulmonary vasculature system
timeFrame: At the time of the procedure
Secondary outcomes:
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Division of Pulmonary, Allergy and Critical Care Medicine
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Michael Risbano, MD
role: PRINCIPAL_INVESTIGATOR
References: