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Pilot Study of Imatinib Mesylate to Treat Nephrogenic Systemic Fibrosis (GENESYF)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2009 by Massachusetts General Hospital.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by:
Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00677092
First received: May 8, 2008
Last updated: March 25, 2009
Last verified: March 2009
History of Changes
  Purpose
  • 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.

Condition Intervention Phase
Nephrogenic Systemic Fibrosis
 Drug: Imatinib mesylate
 Phase 2

Study Type: Interventional
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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Change in modified Rodnan skin score (mRSS) to assess skin tethering [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 12
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)
Arms Assigned Interventions
Experimental: Treatment Drug: Imatinib mesylate
400 mg p.o. daily for four months
Other Name: Gleevec

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00677092

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Novartis Pharmaceuticals
Investigators
Principal Investigator: Jonathan Kay, MD Massachusetts General Hospital
  More Information

Publications:

Responsible Party: Jonathan Kay, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00677092     History of Changes
Other Study ID Numbers: 2007-P-001945
Study First Received: May 8, 2008
Last Updated: March 25, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:
Treatment
Chronic kidney disease
Fibrosing disorders
Imatinib mesylate

Additional relevant MeSH terms:
Fibrosis
Nephrogenic Fibrosing Dermopathy
Pathologic Processes
Skin Diseases
Imatinib
Antineoplastic Agents
 Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 19, 2013