Overview

This trial is active, not recruiting.

Condition nephrogenic systemic fibrosis
Treatment imatinib mesylate
Phase phase 2
Sponsor Massachusetts General Hospital
Collaborator Novartis Pharmaceuticals
Start date May 2008
End date July 2009
Trial size 12 participants
Trial identifier NCT00677092, 2007-P-001945

Summary

- To determine the efficacy of imatinib mesylate in reducing cutaneous thickening and tethering in patients with nephrogenic systemic fibrosis (NSF).

- To assess the safety and tolerability of imatinib mesylate in patients with chronic kidney disease and NSF.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
imatinib mesylate Gleevec
400 mg p.o. daily for four months

Primary Outcomes

Measure
Change in modified Rodnan skin score (mRSS) to assess skin tethering
time frame: 4 months

Secondary Outcomes

Measure
Change in maximal extension of elbows and knees
time frame: 4 months
Change in histologic appearance of skin biopsy
time frame: 4 months
Change in visual analog scale (VAS) for pain
time frame: 4 months
Change in health assessment questionnaire (HAQ) score
time frame: 4 months
Change in SF-36 score
time frame: 4 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Age > 18 years - Biopsy-proven NSF - Ability to give consent Exclusion Criteria: - Known sensitivity to imatinib mesylate or to any of its components - Pregnant or lactating woman - Bullous dermatologic disease - AST/ALT >3 x upper limit of normal - Severe congestive heart failure (NYHA Class III or IV)

Additional Information

Official title An Open Label Phase 2 Pilot Study to Determine the Safety, Efficacy and Tolerability of Gleevec (Imatinib Mesylate) in the Treatment of Nephrogenic Systemic Fibrosis
Principal investigator Jonathan Kay, MD
Description Nephrogenic systemic fibrosis (NSF) is a recently described, extremely debilitating and painful condition that affects individuals with renal failure. Recent reports suggest an association between gadolinium exposure during magnetic resonance (MR) studies and the subsequent development of NSF in patients with chronic renal failure. NSF is characterized by rapidly progressive skin hardening, tethering and hyperpigmentation, predominantly on the extremities. Visceral involvement is rare. Skin biopsies of early NSF lesions demonstrate thickened collagen bundles, mucin deposition, angiogenesis and numerous dermal spindle cells that stain with antibodies to CD34 and procollagen. Cutaneous changes of NSF are present in up to 13% of individuals receiving hemodialysis. Among those patients with clinical evidence of NSF, the principle investigator of this protocol has recently reported that NSF is associated with increased early mortality at 24-months. There is no proven therapy for this devastating disorder. Anecdotal reports have shown modest improvement in joint mobility and decreased skin thickening with extracorporeal photopheresis and pentoxyphylline. Increased TGF-beta1 mRNA on immunostaining has been observed in skin, fascia and striated muscle. Imatinib mesylate, a tyrosine kinase inhibitor, prevents TGF-beta-induced stimulation of collagen and extracellular matrix protein synthesis as well as mRNA expression by normal fibroblasts. This observation led the principal investigator to evaluate imatinib mesylate 400 mg p.o. daily for 1 year in two patients with NSF. The result was significant softening of previously hardened skin with increased mobility of skin that previously had been tethered to the underlying fascia. After one month of imatinib mesylate, one of the two patients had a 20 degree reduction of his knee flexion contractures.
Trial information was received from ClinicalTrials.gov and was last updated in March 2009.
Information provided to ClinicalTrials.gov by Massachusetts General Hospital.