Biomarkers in Pulmonary Arterial Hypertension Treated With Nilotinib

This study is ongoing, but not recruiting participants.

Sponsor:

Information provided by (Responsible Party):

Kewal Asosingh, Ph.D, The Cleveland Clinic

ClinicalTrials.gov Identifier:

NCT01320865

First received: March 18, 2011

Last updated: June 8, 2012

Last verified: June 2012

History of Changes

Purpose

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.

Condition
PAH

Study Type:	Observational
Study Design:	Observational Model: Cohort Time Perspective: Prospective

Resource links provided by NLM:

Genetics Home Reference related topics: pulmonary arterial hypertension

MedlinePlus related topics: High Blood Pressure

Drug Information available for: Nilotinib

U.S. FDA Resources

Further study details as provided by The Cleveland Clinic:

Primary Outcome Measures:

Measuring circulating markers of Nilotinib affect [ Time Frame: within one year of the end of the study ] [ Designated as safety issue: No ]
We will measure markers of mast cell activation in blood and urine before and during treatment with nilotinib.

Secondary Outcome Measures:

Evaluate effect of Nilotinib on the activation of mast cells. [ Time Frame: within one year of the end of the study ] [ Designated as safety issue: No ]
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.

Estimated Enrollment:	66
Study Start Date:	August 2010
Estimated Study Completion Date:	January 2013
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Groups/Cohorts
Subjects with PAH treated with nilotinib

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01320865

Locations

United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195

Sponsors and Collaborators

The Cleveland Clinic

Investigators

Principal Investigator:

Kewal Asosingh, Ph.D

The Cleveland Clinic

More Information

Additional Information:

See Study: Efficacy, Safety, Tolerabilitiy and PK of AMN 107 in PAH This link exits the ClinicalTrials.gov site

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. No abstract available.

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.

Responsible Party:	Kewal Asosingh, Ph.D, Associate Staff, The Cleveland Clinic
ClinicalTrials.gov Identifier:	NCT01320865 History of Changes
Other Study ID Numbers:	Novartis AMN-107
Study First Received:	March 18, 2011
Last Updated:	June 8, 2012
Health Authority:	United States: Institutional Review Board

ClinicalTrials.gov processed this record on May 19, 2013

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