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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT00677092
Other study ID # 2007-P-001945
Secondary ID
Status Active, not recruiting
Phase Phase 2
First received May 8, 2008
Last updated March 25, 2009
Start date May 2008
Est. completion date July 2009

Study information

Verified date March 2009
Source Massachusetts General Hospital
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 12
Est. completion date July 2009
Est. primary completion date July 2009
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility 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)

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Intervention

Drug:
Imatinib mesylate
400 mg p.o. daily for four months

Locations

Country Name City State
United States Massachusetts General Hospital Boston Massachusetts

Sponsors (2)

Lead Sponsor Collaborator
Massachusetts General Hospital Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (5)

Kay J, Bazari H, Avery LL, Koreishi AF. Case records of the Massachusetts General Hospital. Case 6-2008. A 46-year-old woman with renal failure and stiffness of the joints and skin. N Engl J Med. 2008 Feb 21;358(8):827-38. doi: 10.1056/NEJMcpc0708697. — View Citation

Kay J, High WA. Imatinib mesylate treatment of nephrogenic systemic fibrosis. Arthritis Rheum. 2008 Aug;58(8):2543-8. doi: 10.1002/art.23696. — View Citation

Kay J. Gadolinium and nephrogenic systemic fibrosis: the evidence of things not seen. Cleve Clin J Med. 2008 Feb;75(2):112, 114, 117. Review. — View Citation

Kay J. Nephrogenic systemic fibrosis: a gadolinium-associated fibrosing disorder in patients with renal dysfunction. Ann Rheum Dis. 2008 Dec;67 Suppl 3:iii66-9. doi: 10.1136/ard.2008.102475. Review. — View Citation

Todd DJ, Kagan A, Chibnik LB, Kay J. Cutaneous changes of nephrogenic systemic fibrosis: predictor of early mortality and association with gadolinium exposure. Arthritis Rheum. 2007 Oct;56(10):3433-41. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Change in modified Rodnan skin score (mRSS) to assess skin tethering 4 months No
Secondary Change in maximal extension of elbows and knees 4 months No
Secondary Change in histologic appearance of skin biopsy 4 months No
Secondary Change in visual analog scale (VAS) for pain 4 months No
Secondary Change in health assessment questionnaire (HAQ) score 4 months No
Secondary Change in SF-36 score 4 months No
See also
  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