Biomarkers in Pulmonary Arterial Hypertension Treated With Nilotinib

Tracking Information
First Submitted Date	March 18, 2011
First Posted Date	March 23, 2011
Last Update Posted Date	February 4, 2014
Study Start Date	August 2010
Actual Primary Completion Date	December 2012 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures; (submitted: March 21, 2011)	Measuring circulating markers of Nilotinib affect [ Time Frame: within one year of the end of the study ]; We will measure markers of mast cell activation in blood and urine before and during treatment with nilotinib.
Original Primary Outcome Measures	Same as current
Change History	Complete list of historical versions of study NCT01320865 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures; (submitted: March 21, 2011)	Evaluate effect of Nilotinib on the activation of mast cells. [ Time Frame: within one year of the end of the study ]; We will measure markers of mast cell activation in blood and urine before and during treatment with nilotinib. We will also look at the proliferation of mast cell progenitors and correlate this to clinical markers used to monitor this disease.
Original Secondary Outcome Measures	Same as current
Current Other Outcome Measures	Not Provided
Original Other Outcome Measures	Not Provided
Descriptive Information
Brief Title	Biomarkers in Pulmonary Arterial Hypertension Treated With Nilotinib
Official Title	Not Provided
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.
Detailed Description	Not Provided
Study Type	Observational
Study Design	Observational Model: Cohort; Time Perspective: Prospective
Target Follow-Up Duration	Not Provided
Biospecimen	Not Provided
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
Condition	PAH
Intervention	Not Provided
Study Groups/Cohorts	Subjects with PAH treated with nilotinib
Publications *	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.; 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.; 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. Epub 2007 Feb 8.; Heath D, Yacoub M. Lung mast cells in plexogenic pulmonary arteriopathy. J Clin Pathol. 1991 Dec;44(12):1003-6.; 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.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status	Withdrawn
Actual Enrollment; (submitted: February 3, 2014)	0
Original Estimated Enrollment; (submitted: March 21, 2011)	66
Actual Study Completion Date	December 2012
Actual Primary Completion Date	December 2012 (Final data collection date for primary outcome measure)
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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries	United States
Removed Location Countries
Administrative Information
NCT Number	NCT01320865
Other Study ID Numbers	Novartis AMN-107
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Kewal Asosingh, Ph.D, The Cleveland Clinic
Study Sponsor	The Cleveland Clinic
Collaborators	Not Provided
Investigators	Principal Investigator: Kewal Asosingh, Ph.D The Cleveland Clinic
PRS Account	The Cleveland Clinic
Verification Date	February 2014