Imatinib in Systemic Sclerosis
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.
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot Study of Imatinib in the Treatment of Refractory Systemic Sclerosis|
- 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.
- 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 ]
|Study Start Date:||July 2007|
|Primary Completion Date:||September 2010 (Final data collection date for primary outcome measure)|
Experimental: Imatinib mesylate
100 mg daily and increase by 100mg daily every 2 weeks to a maximum of 400 mg daily as tolerated
Drug: Imatinib mesylate
100 mg orally daily increased by 100 mg/day every 2 weeks to maximum of 400 mg daily as tolerated. Treatment for 6 months total.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00506831
|United States, California|
|Stanford University School of Medicine|
|Stanford, California, United States, 94305|
|Principal Investigator:||Lorinda S Chung||Stanford University|