Biomarkers in Pulmonary Arterial Hypertension Treated With Nilotinib

NCT01320865 | Withdrawn

• 1 other identifier: Novartis AMN-107
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 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.

Conditions

PAH

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Evaluate effect of Nilotinib on the activation of mast cells.

  within one year of the end of the study

Study Arms (1)

Subjects with PAH treated with nilotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• 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?

You may not qualify if:

• 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

Sponsors & Collaborators

• The Cleveland Clinic: lead

Study Sites (1)

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Related Publications (5)

• 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.

  PMID: 16847299 BACKGROUND

• 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.

  PMID: 16200212 BACKGROUND

• 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.

  PMID: 17289809 BACKGROUND

• 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.

  PMID: 1791199 BACKGROUND

• 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.

  PMID: 10508822 BACKGROUND

Related Links

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

Study Officials

• Kewal Asosingh, Ph.D

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Staff

Study Record Dates

• First Submitted: March 18, 2011
• First Posted: March 23, 2011
• Study Start: August 1, 2010
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: February 4, 2014

Record last verified: 2014-02

Locations

US (1)