Nephrogenic Systemic Fibrosis Clinical Trial
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
- 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.
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.
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Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT00981942 -
Treatment of Patients With Nephrogenic Systemic Fibrosis With Glivec
|
Phase 3 | |
Completed |
NCT01135316 -
Prospective Evaluation of the Incidence of NSF in Patients With Kidney Disease Undergoing MR
|
N/A | |
Completed |
NCT00869479 -
Validation of a Questionnaire to Identify Signs and Symptoms of Nephrogenic Systemic Fibrosis
|
N/A | |
Enrolling by invitation |
NCT01359345 -
Nephrogenic Systemic Fibrosis With Gadollinum
|
Phase 2/Phase 3 | |
Withdrawn |
NCT00811863 -
Evaluation of Nephrogenic Systemic Fibrosis (NSF) in Patients With Chronic Kidney Disease Following OptiMARK Injection
|
N/A | |
Terminated |
NCT01078987 -
Plasmapheresis for Nephrogenic Fibrosing Dermopathy (NFD)/Nephrogenic Systemic Fibrosis (NSF)
|
Phase 4 | |
Completed |
NCT01014754 -
Nephrogenic Systemic Fibrosis (NSF): Analysis of Tissue Gadolinium Levels
|
N/A |