Skip to main content
OpenTrials
Completed

NCT Number: NCT00677092

Pilot Study of Imatinib Mesylate to Treat Nephrogenic Systemic Fibrosis

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

About this study

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 cluster of differentiation 34 (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 transforming growth factor (TGF)-beta1 messenger ribonucleic acid (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 milligrams (mg) orally (p.o.) daily for 1 year in two participants 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 participants had a 20 degree reduction of his knee flexion contractures.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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
  • 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

Treatment and study plan

imatinib mesylate

Drug

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

Other names: Gleevec

Primary outcomes

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

    Time frame: Baseline and Month 4

    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.

Secondary outcomes

  1. Change From Baseline in Maximal Extension of Elbows and Knees

    Time frame: Baseline and Month 4

  2. Change From Baseline in Histologic Appearance of Skin Biopsy

    Time frame: Baseline and Month 4

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

    Time frame: Baseline and Month 4

  4. Change From Baseline in Health Assessment Questionnaire (HAQ) Score

    Time frame: Baseline and Month 4

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

    Time frame: Baseline and Month 4

Sponsors and collaborators

Lead sponsor

Massachusetts General Hospital

Other

Collaborators

  • Novartis Pharmaceuticals

Registry information

Official study 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

Acronym: GENESYF

Important dates

Study start
2007
Primary completion
2009
Study completion
2009
First posted
May 13, 2008
Registry last updated
May 19, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.