Pilot Study of Imatinib Mesylate to Treat Nephrogenic Systemic Fibrosis (GENESYF)
- 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.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|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|
- Change in modified Rodnan skin score (mRSS) to assess skin tethering [ Time Frame: 4 months ] [ Designated as safety issue: No ]
- Change in maximal extension of elbows and knees [ Time Frame: 4 months ] [ Designated as safety issue: No ]
- Change in histologic appearance of skin biopsy [ Time Frame: 4 months ] [ Designated as safety issue: No ]
- Change in visual analog scale (VAS) for pain [ Time Frame: 4 months ] [ Designated as safety issue: No ]
- Change in health assessment questionnaire (HAQ) score [ Time Frame: 4 months ] [ Designated as safety issue: No ]
- Change in SF-36 score [ Time Frame: 4 months ] [ Designated as safety issue: No ]
|Study Start Date:||May 2008|
|Estimated Study Completion Date:||July 2009|
|Estimated Primary Completion Date:||July 2009 (Final data collection date for primary outcome measure)|
Drug: Imatinib mesylate
400 mg p.o. daily for four months
Other Name: Gleevec
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00677092
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Principal Investigator:||Jonathan Kay, MD||Massachusetts General Hospital|