Biomarkers in Pulmonary Arterial Hypertension Treated With Nilotinib

PAH Clinical Trial

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01320865
• Other study ID #: Novartis AMN-107
• Status: Withdrawn
• Phase: N/A
• First received: March 18, 2011
• Last updated: February 3, 2014
• Start date: August 2010
• Est. completion date: December 2012

Study information

• Verified date: February 2014
• Source: The Cleveland Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• PAH

Locations

Country	Name	City	State
United States	Cleveland Clinic	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
The Cleveland Clinic

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View 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. — View Citation

Heath D, Yacoub M. Lung mast cells in plexogenic pulmonary arteriopathy. J Clin Pathol. 1991 Dec;44(12):1003-6. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measuring circulating markers of Nilotinib affect	We will measure markers of mast cell activation in blood and urine before and during treatment with nilotinib.	within one year of the end of the study	No
Secondary	Evaluate effect of Nilotinib on the activation of mast cells.	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.	within one year of the end of the study	No

External Links

•   See Study: Efficacy, Safety, Tolerabilitiy and PK of AMN 107 in PAH