Clinical trial NCT01320865: Biomarkers in Pulmonary Arterial Hypertension Treated With Nilotinib
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: PAH
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
First posted: 2011-03-23
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients diagnosed with PAH that are enrolled in the Nilotinib clinical trial. http://clinicaltrials.gov/ct2/show/NCT01179737?term=tasigna+and+pulmonary+hypertension\&rank=1

Brief summary: The investigators 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, the investigators hypothesize that anti cKit tyrosine kinase inhibitor (TKI), nilotinib, provides clinical benefit to patients through inhibition of mast cell progenitor proliferation, mobilization and differentiation. To test this, the investigators will determine if mast cell progenitors and mast cell biomarkers are related to nilotinib clinical response. This will be an ancillary study, part of a placebo-controlled, double-blind multi center clinical trial of nilotinib in pulmonary arterial hypertension.


Eligibility criteria: Inclusion Criteria:

This study is a substudy and subjects must be enrolled in the main trial:

See Study Efficacy, Safety, Tolerability and Pharmacokinetics (PK) of Nilotinib (AMN107) in Pulmonary Arterial Hypertension (PAH) In clinical trials. (clinical Trial ID NCT01179737)

http://clinicaltrials.gov/ct2/show/NCT01179737?

Exclusion Criteria:

Subjects are not enrolled in the main study:

See Study Efficacy, Safety, Tolerability and Pharmacokinetics (PK) of Nilotinib (AMN107) in Pulmonary Arterial Hypertension (PAH) In clinical trials. (clinical Trial ID NCT01179737)

http://clinicaltrials.gov/ct2/show/NCT01179737?term=tasigna+and+pulmonary+hypertension\&rank=1

Primary outcomes:
measure: Measuring circulating markers of Nilotinib affect
timeFrame: within one year of the end of the study
Secondary outcomes:
measure: Evaluate effect of Nilotinib on the activation of mast cells.
timeFrame: within one year of the end of the study
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Kewal Asosingh, Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Patterson KC, Weissmann A, Ahmadi T, Farber HW. Imatinib mesylate in the treatment of refractory idiopathic pulmonary arterial hypertension. Ann Intern Med. 2006 Jul 18;145(2):152-3. doi: 10.7326/0003-4819-145-2-200607180-00020. No abstract available.
citation: Schermuly RT, Dony E, Ghofrani HA, Pullamsetti S, Savai R, Roth M, Sydykov A, Lai YJ, Weissmann N, Seeger W, Grimminger F. Reversal of experimental pulmonary hypertension by PDGF inhibition. J Clin Invest. 2005 Oct;115(10):2811-21. doi: 10.1172/JCI24838.
citation: Dentelli P, Rosso A, Balsamo A, Colmenares Benedetto S, Zeoli A, Pegoraro M, Camussi G, Pegoraro L, Brizzi MF. C-KIT, by interacting with the membrane-bound ligand, recruits endothelial progenitor cells to inflamed endothelium. Blood. 2007 May 15;109(10):4264-71. doi: 10.1182/blood-2006-06-029603. Epub 2007 Feb 8.
citation: Heath D, Yacoub M. Lung mast cells in plexogenic pulmonary arteriopathy. J Clin Pathol. 1991 Dec;44(12):1003-6. doi: 10.1136/jcp.44.12.1003.
citation: Hamada H, Terai M, Kimura H, Hirano K, Oana S, Niimi H. Increased expression of mast cell chymase in the lungs of patients with congenital heart disease associated with early pulmonary vascular disease. Am J Respir Crit Care Med. 1999 Oct;160(4):1303-8. doi: 10.1164/ajrccm.160.4.9810058.