Ignite Creation Date:
2024-05-06 @ 1:00 PM
Last Modification Date:
2024-10-26 @ 1:07 PM
Study NCT ID:
NCT03905083
Status:
WITHDRAWN
Last Update Posted:
2022-03-03
First Post:
2019-02-25
Brief Title:
miRNA and Myokines in Patients With PAH
Sponsor:
University of Pittsburgh
Organization:
University of Pittsburgh
Study Overview
Official Title:
miRNA and Myokines Acutely-expressed During Exercise in Patients With Pulmonary Arterial Hypertension
Status:
WITHDRAWN
Status Verified Date:
2021-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Logistics related to research activity
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None