Biomarkers in Pulmonary Arterial Hypertension Treated With Imatinib

The Cleveland Clinic8 sites in 1 country130 target enrollmentMarch 2010

ConditionsPAH

Overview

Phase: Not Applicable
Intervention: Not specified
Conditions: PAH
Sponsor: The Cleveland Clinic
Enrollment: 130
Locations: 8
Primary Endpoint: Measuring circulating biomarkers of imatinib affect
Status: Completed
Last Updated: 12 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of the study is to determine whether circulating molecular and cellular biomarkers are predictive of imatinib effect on pulmonary artery hypertension.

Detailed Description

We hypothesize that bone marrow progenitor cells are mobilized into the circulation in PAH, home to the lungs and differentiate into mast cells, which promote vascular remodeling and vasoconstriction through release of renin and chymase. As a corollary to this, we hypothesize that anti cKit tyrosine kinase inhibitor (TKI), imatinib, provides clinical benefit to patients through inhibition of mast cell progenitor proliferation, mobilization and differentiation. To test this, we will determine if mast cell progenitors and mast cell biomarkers are related to imatinib clinical response. This will be an ancillary study, part of a placebo-controlled, double-blind multi center clinical trial of imatinib in pulmonary arterial hypertension.

Registry

clinicaltrials.gov

Start Date

March 2010

End Date

December 2012

Last Updated

12 years ago

Study Type

Observational

Sex

All

Investigators

Sponsor

The Cleveland Clinic

Responsible Party

Principal Investigator

Kewal Asosingh, Ph.D

Associate Staff

The Cleveland Clinic

Eligibility Criteria

Inclusion Criteria

•from Imatinib Trial
•Male or Female 18 years or older
•A current diagnosis or Pulmonary Arterial Hypertension according to the Dana Point 2008 Meeting: WHO Diagnostic Group I, idiopathic or heritable (familial or sporadic) PAH, PAH associated with collagen vascular disease including systemic sclerosis, rheumatoid arthritis, mixed connective tissue diseases, and overlap syndrome. PAH following one year repair of congenital heart defect (ASD, VSD, or PDA), or PAH associated with diet therapies or other drugs
•A PVR\>1000dynes.sec.cm-5(as assess by RHC at screening or in the 2 months preceding the screening visit despite treatment with two or more specific PAH therapies, including endothelin receptor antagonists (ERA), phosphodiesterase 5 inhibitors (PDE5), or inhaled, intravenous or oral prostacyclin analogues for ≥3 months. On stable background therapy doses for ≥ 30 days except for warfarin (≥30 days but doses can vary even within the mouth before enrollment)
•WHO Functional Class II-IV. For WHO Functional Class IV, one of the 2 or more specific PAH therapies must be an inhaled, intravenous or oral prostacyclin analogue, unless the subject has been shown to be intolerant of prostacyclin analogues.
•6MWD≥150meters and ≥450meters at screening. Distances of two consecutive 6MWTs should be within 15% of one another.
•Ability to provide written informed consent

Exclusion Criteria

•from Imatinib Trial
•Women of childbearing potential who are not practicing birth control methods.
•Pregnant or nursing (lactating) women, where pregnancy is defined as the state of positive hCG laboratory test (\> 5 mIU/MI)
•Have previously received treatment with imatinib
•In treatment with chronic nitric oxide therapy
•Pre-existing lung disease including parasitic diseases affecting lungs, congenital abnormalities of the lungs, thorax or diaphragm or bronchial asthma associated with chronic hypoxia that may contribute to severity of PAH
•With a pulmonary capillary wedge pressure \>15 mm Hg to rule out PAH secondary to left ventricular dysfunction
•With a diagnosis of pulmonary artery or vein stenosis
•With other diagnosis of PAH in WHO Diagnostic Group 1 re excluded including congenital systemic to pulmonary shunts (large, small that not surgically repaired, portal hypertension, HIV infection, glycogen storage disease, Gaucher's disease, hereditary hemorrhagic telangiectasia, hemoglobinopthaies, myeloproliferative disorders)
•With a diagnosis of PAH associated with: venous hypertension (WHO Diagnostic Group II), hypoxia (WHO Diagnostic Group III), chronic pulmonary thromboembolic disease (WHO Diagnostic Group IV) or other miscellaneous causes (WHO Diagnostic Class V, which includes sarcoidosis, histiocytosis X, lympangiomatosis, compression of pulmonary vessels).