William Robinson
Imatinib in Systemic Sclerosis
Contact Information
Stanford University School of Medicine 300 Pasteur Drive Stanford, CA 94305Brief
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.
Recruiting Status:
RecruitingStanford Recruiting Status:
RecruitingCondition(s):
Intervention(s):
- Drug: Imatinib mesylate
Phase:
Phase 1/Phase 2Eligibility
Ages Eligible for Study:
18 years to 80 yearsGenders Eligible for Study:
Male and FemaleHealth of Volunteers:
People with the conditions listed in this trial can participate as controls.Key Inclusion Criteria:
Adults with refractory diffuse or limited SSc and any or all of the following: Progressive cutaneous fibrosis, Interstitial lung disease, Pulmonary arterial hypertension, Digital ulcerations.
Key Exclusion Criteria:
Uncontrolled congestive heart failure, hypertension, or coronary artery disease.
HIV, hepatitis B, and/or hepatitis C infection.
Serious infection within the past month.
Significant hematologic, renal, or hepatic abnormalities.
Concurrent use of intravenous immunoglobulin or cyclophosphamide within 4 weeks of the first treatment dose.
Concurrent use of a biologic agent (ie. etanercept, infliximab, adalimumab, abatacept) within 8 weeks of the first treatment dose (6 months for rituximab).
Women who are pregnant or breastfeeding.
Additional Study Details
Official Title:
A Pilot Study of Imatinib in the Treatment of Refractory Systemic SclerosisAnticipated start date:
7/24/2007Lead Sponsor:
Stanford UniversityInvestigator(s):
Study Type:
InterventionalPurpose:
TreatmentAllocation:
Non-randomizedMasking:
OpenControl:
noneAssignment:
Single GroupEndpoints:
Safety/EfficacyPrimary Outcomes:
- Change in modified Rodnan skin score at 6 months compared to baseline
Secondary Outcomes:
- Change in Pulmonary Function Tests at 6 months compared to baseline
- Change in digital ulcerations at 6 months compared to baseline
- Change in Scleroderma Health Assessment Questionnaire at 6 months compared to baseline
- Change in dermal thickness and collagen separation on cutaneous histopathology at 6 months compared to baseline
- Change in serum cytokine profile at 6 months compared to baseline
- Change in high throughput gene expression analysis at 6 months compared to baseline
- Change in serum autoantibody profile at 6 months compared to baseline
Total Number to be Enrolled:
15Total Number to be Enrolled at Stanford:
15More Information
Secondary ID(s):
- 9598
Locations & Contacts
Stanford Locations & Contacts:
Stanford University School of Medicine 300 Pasteur Drive Stanford, CA 94305Non-Stanford Locations:
The Stanford website does not have any locations outside of Stanford listed for this trial. You may want to check clinicaltrials.gov for posible additional locations.
This listing was last updated:
1/18/2008PLEASE NOTE:
Study Coordinators and Research Nurses cannot give medical advice over the phone. Telephone numbers are provided for obtaining additional information on specific clinical research trials only. If you have specific questions which require clinical expertise, please call your primary care physician. If you do not have a primary care physician please feel free to call the SHC Physician Referral Service at (800) 756-9000 or send an email.
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