Clinical Trial: Imatinib in Systemic Sclerosis

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Pilot Study of Imatinib in the Treatment of Refractory Systemic Sclerosis

Brief Summary:

Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs and widespread vasculopathy. Patients with SSc are classified according to the extent of cutaneous sclerosis: patients with limited SSc have skin thickening of the face, neck, and distal extremities, while those with diffuse SSc have involvement of the trunk, abdomen, and proximal extremities as well. The disease course varies depending on the subtype of SSc. However, common features that result in significant morbidity and mortality, in addition to cutaneous fibrosis, include Raynaud's phenomenon and digital ulcerations, interstitial lung disease (ILD), and pulmonary arterial hypertension (PAH). Current therapeutic options for patients with SSc and these clinical manifestations have shown limited efficacy.

Imatinib antagonizes specific tyrosine kinases that mediate fibrotic pathways involved in the pathogenesis of SSc, including c-Abl, a downstream mediator of transforming growth factor (TGF)-beta, and platelet derived growth factor (PDGF) receptors. The efficacy of imatinib has also been reported in the treatment of patients with refractory idiopathic PAH through its effects on vascular remodeling. Based on the mechanism of action and preliminary patient data, we hypothesize that imatinib may be effective in the treatment of the fibrotic and vasculopathic features of patients with SSc. This is an open label pilot study to evaluate the safety and efficacy of imatinib in patients with progressive SSc refractory to other treatment(s). Validated measures of skin thickness and disease activity will be determined over 6-months of therapy and compared with baseline measures.


Detailed Summary:
Sponsor: Stanford University

Current Primary Outcome: Percent Change in Modified Rodnan Skin Score at 6 Months Compared to Baseline [ Time Frame: 6 months compared to baseline ]

Modified Rodnan skin score (mRSS) on scale of 0 (no skin disease) to 51 severe skin disease. %change in mRSS=(score at 6 months - baseline score)/baseline score. Negative values indicate improvement in skin disease. Clinical important improvement defined as > 25% improvement.


Original Primary Outcome: Change in modified Rodnan skin score [ Time Frame: 6 months compared with baseline ]

Current Secondary Outcome:

  • Change in Pulmonary Function Tests at 6 Months Compared to Baseline [ Time Frame: 6 months compared to baseline ]
  • Change in Digital Ulcerations at 6 Months Compared to Baseline [ Time Frame: 6 months compared to baseline ]
  • Change in Scleroderma Health Assessment Questionnaire at 6 Months Compared to Baseline [ Time Frame: 6 months compared to baseline ]
  • Change in Dermal Thickness and Collagen Separation on Cutaneous Histopathology at 6 Months Compared to Baseline [ Time Frame: 6 months compared to baseline ]
  • Change in Serum Cytokine Profile at 6 Months Compared to Baseline [ Time Frame: 6 months compared to baseline ]
  • Change in High Throughput Gene Expression Analysis at 6 Months Compared to Baseline [ Time Frame: 6 months compared to baseline ]
  • Change in Serum Autoantibody Profile at 6 Months Compared to Baseline [ Time Frame: 6 months compared to baseline ]


Original Secondary Outcome:

  • Change in Pulmonary Function Tests [ Time Frame: 6 months compared with baseline ]
  • Change in digital ulcerations [ Time Frame: 6 months compared with baseline ]
  • Change in Scleroderma Health Assessment Questionnaire [ Time Frame: 6 months compared with baseline ]
  • Change in dermal thickness and collagen separation on cutaneous histopathology [ Time Frame: 6 months compared with baseline ]
  • Change in serum cytokine profile [ Time Frame: 6 months compared with baseline ]
  • Change in high throughput gene expression analysis [ Time Frame: 6 months compared with baseline ]
  • Change in serum autoantibody profile [ Time Frame: 6 months compared with baseline ]


Information By: Stanford University

Dates:
Date Received: July 24, 2007
Date Started: July 2007
Date Completion:
Last Updated: July 10, 2012
Last Verified: July 2012