Pilot Study of Imatinib Mesylate to Treat Nephrogenic Systemic Fibrosis

NCT00677092 | Completed Phase 2 Results

• 1 other identifier: 2007-P-001945
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the efficacy of imatinib mesylate in reducing cutaneous thickening and tethering in patients with nephrogenic systemic fibrosis (NSF). The study will also work to assess the safety and tolerability of imatinib mesylate in patients with chronic kidney disease and NSF.

Conditions

Nephrogenic Systemic Fibrosis

Keywords

Treatment; Chronic kidney disease; Fibrosing disorders; Imatinib mesylate

Outcome Measures

Primary Outcomes (1)

• Percentage Change From Baseline in the Modified Rodnan Skin Score (mRSS) to Assess Skin Tethering

  The modified Rodnan Skin Score is the accepted clinical measure of scleroderma skin activity. The investigator assessed the thickening of the skin using the modified Rodnan Skin Score through simple palpation on 17 different skin sites in the fingers, hands, forearms, arms, feet, legs, and thighs (bilaterally) and face, chest, and abdomen (singly). Skin thickness was assessed on a scale of 0 to 3; 0 representing normal skin and 3 being severe thickening. The sum of the individual scores can range from 0 (normal) to 51 (severe thickening in all 17 areas). Percentage change is calculated as the Month 4 Score - Baseline Score/Baseline Score \* 100. A negative percentage change indicates improvement.

  Baseline and Month 4

Secondary Outcomes (5)

• Change From Baseline in Maximal Extension of Elbows and Knees

  Baseline and Month 4

• Change From Baseline in Histologic Appearance of Skin Biopsy

  Baseline and Month 4

• Change From Baseline in Visual Analog Scale (VAS) for Pain

  Baseline and Month 4

• Change From Baseline in Health Assessment Questionnaire (HAQ) Score

  Baseline and Month 4

• Change From Baseline in Short Form 36 (SF-36) Score

  Baseline and Month 4

Study Arms (1)

Imatinib Mesylate (IM) Treatment

EXPERIMENTAL

Imatinib mesylate 400 milligrams (mg) orally once daily for 4 months. Dosage was reduced to 200 mg if the participant developed gastrointestinal intolerance or alopecia.

Drug: Imatinib mesylate

Interventions

Imatinib mesylate DRUG

400 mg p.o. daily for 4 months. Dosage was reduced to 200 mg if participants develop gastrointestinal intolerance or alopecia.

Also known as: Gleevec

Imatinib Mesylate (IM) Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years
• Biopsy-proven NSF
• Ability to give consent

You may not qualify if:

• Known sensitivity to imatinib mesylate or to any of its components
• Pregnant or lactating woman
• Bullous dermatologic disease
• Aspartate aminotransferase / alanine aminotransferase (AST/ALT) \>3 x upper limit of normal
• Severe congestive heart failure \[New York Heart Association (NYHA) Class III or IV\]
• Patients who have received Gleevec in the past 12 months

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (5)

• 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. doi: 10.1002/art.22925.

  PMID: 17907148 BACKGROUND

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

  PMID: 18668587 BACKGROUND

• Kay J, Czirjak L. Gadolinium and systemic fibrosis: guilt by association. Ann Rheum Dis. 2010 Nov;69(11):1895-7. doi: 10.1136/ard.2010.134791. No abstract available.

  PMID: 20959325 BACKGROUND

• Schmidt-Lauber C, Bossaller L, Abujudeh HH, Vladimer GI, Christ A, Fitzgerald KA, Latz E, Gravallese EM, Marshak-Rothstein A, Kay J. Gadolinium-based compounds induce NLRP3-dependent IL-1beta production and peritoneal inflammation. Ann Rheum Dis. 2015 Nov;74(11):2062-9. doi: 10.1136/annrheumdis-2013-204900. Epub 2014 Jun 9.

  PMID: 24914072 BACKGROUND

• Todd DJ, Kay J. Gadolinium-Induced Fibrosis. Annu Rev Med. 2016;67:273-91. doi: 10.1146/annurev-med-063014-124936.

  PMID: 26768242 BACKGROUND

MeSH Terms

Conditions

Nephrogenic Fibrosing Dermopathy; Renal Insufficiency, Chronic

Interventions

Imatinib Mesylate

Condition Hierarchy (Ancestors)

Skin Diseases; Skin and Connective Tissue Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Limitations and Caveats

PI left institution in 2009; Data collected cannot be associated with specific participants and analyzed for secondary outcome measure or adverse event data entry.

Results Point of Contact

• Title: Jonathan Kay, MD
• Organization: University of Massachusetts Medical School

jonathan.kay@umassmemorial.org

508-793-6936

Study Officials

• Jonathan Kay, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 8, 2008
• First Posted: May 13, 2008
• Study Start: December 1, 2007
• Primary Completion: July 1, 2009
• Study Completion: July 1, 2009
• Last Updated: May 19, 2017
• Results First Posted: May 19, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)