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Treatment of Patients With Nephrogenic Systemic Fibrosis With Glivec (NSF)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Aarhus
ClinicalTrials.gov Identifier:
NCT00981942
First received: September 21, 2009
Last updated: June 4, 2012
Last verified: June 2012
History of Changes
  Purpose

The investigators will study the effect of imatinib mesylate (Glivec) in treatment of moderate to severe nephrogenic systemic fibrosis (NSF).

So far there is no evidence of adequately effective treatment options of NSF. Various treatments have been tried to stop the progressing disease. Corticosteroids, which suppress the early inflammatory stage of the disease, fail to halt disease progression.

Other immunosuppressive agents, photopheresis, and kidney transplantations are reported to be partly beneficial to the patients.

It has not been possible to confirm these findings in further studies because in photopheresis, and kidney transplantation, such effects are generally unreproducible.


Condition Intervention Phase
Nephrogenic Systemic Fibrosis
 Drug: Imatinib mesylate (Glivec)
 Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Clinical Trial of Imatinib Mesylate(Glivec)in Patients With Moderate to Severe Nephrogenic Systemic Fibrosis

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Aarhus:

Primary Outcome Measures:
  • The primary endpoints are skin fibrosis and joint mobility. [ Time Frame: 16 weeks or 28 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The secondary endpoint is and joint mobility. [ Time Frame: 16 weeks or 28 weeks ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: September 2009
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Imatinib mesylate (Glivec)
    400 mg, one tablet daily for 12 or 24 weeks
    Other Names:
    • Glivec
    • Gleevec
Detailed Description:

NSF is a relatively newly defined fibrosing disease not described before 1997 where the Gadolinium-based contrast agents (GBCAs) were introduced in patients with kidney disease. The association between NSF and GBCA has in many studies shown to be very strong. Until recently, radiologists believed that commercially available GBCAs were safe to use whether the renal function was normal or not. Since the 1980s, >200 million patients have been given these agents. Lately, the occurrence of NSF, a relatively new chronic disorder, has given serious speculations about the safety of these drugs and has questioned their future use. First identified in 1997, but not described until 2000, NSF has been reported only in patients with acute or chronic severe renal insufficiency (with a glomerular filtration rate <30 ml/min/1.73 m2).

Fibrosis in the subcutis means that the skin hardens and loses flexibility. Hard dermal plaque changes often appear on legs, arms and abdomen together with dyspigmentation. As the lesions involve the deep part of the subcutis the muscles are often affected. Involvement of the joints leads to contractures and narrowing of movement. Patients with massive affection of the joints often end up with a zimmer frame or in a wheelchair. The connecting tissue in the inner vital organs may also be affected and NSF can accelerate the death of the patient. The retained gadolinium in lesions of NSF can be found years after administration.

Interestingly, a case report suggests beneficial effects of imatinib mesylate in two patients. Two other independent case reports also show promising results.

Imatinib mesylate inhibits several tyrosine kinases involved in the fibrotic reaction, which is one of the main pathogenetic components of NSF.

  Eligibility

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

Inclusion criteria:

  1. Age > 18 years
  2. Diagnosed with NSF
  3. mRodnan skin score => 20 or
  4. Rapid progression of the disease defined as a 50% increase in mRodnan skin score in less than 7 weeks or
  5. Progression of the fibrosis in the inner organs ex. the heart or the lungs, AND
  6. No absolute contraindications to the treatment

Exclusion Criteria:

  1. Known sensitivity to Imatinib mesylate or to any of its components
  2. Pregnant or lactating woman
  3. ALAT > 3 x upper limit of normal
  4. Severe congestive heart failure (NYHA Class III or IV)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00981942

Locations
Denmark
Department of Dermatology
Aarhus, Denmark, 8000
Sponsors and Collaborators
University of Aarhus
Investigators
Principal Investigator: Anne B Olesen, MD,PhD Anne Braae Olesen
  More Information

Publications:

Responsible Party: University of Aarhus
ClinicalTrials.gov Identifier: NCT00981942     History of Changes
Other Study ID Numbers: 22505 TRE
Study First Received: September 21, 2009
Last Updated: June 4, 2012
Health Authority: Denmark: Danish Dataprotection Agency
Denmark: Danish Medicines Agency
Denmark: Ethics Committee

Keywords provided by University of Aarhus:
Nephrogenic systemic fibrosis
Imatinib mesylate
Glivec
Gleevec

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