Effect of Bosentan on Skin Fibrosis in Patients With Systemic Sclerosis

• Status: Completed
• Trial end date: 2007-05-01
• Target enrollment: 0
• Participant gender: All

Summary

Endothelin-1 is a potent vasoconstrictor and binds to two receptors, ET-A and ET-B, which are variable expressed on endothelial cells, smooth muscle cells, and fibroblasts. Furthermore, endothelin-1 has been found to be released in vitro by scleroderma fibroblasts and could contribute to the development of dermal fibrosis in systemic sclerosis. Bosentan is a dual receptor antagonist, that competes with the binding of endothelin-1 to both receptors and has already been approved for the treatment of pulmonary arterial hypertension in Europe, the US, and some other countries. The purpose of this study is to evaluate the effect of bosentan treatment on skin fibrosis and functionality in patients with systemic sclerosis.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Heinrich-Heine University, Duesseldorf
• Treatments: Bosentan; Endothelin Receptor Antagonists

Criteria

Inclusion Criteria:

• Patients with systemic sclerosis (diffuse SSc, limited SSc)

• ACR criteria fulfilled

• Current areas of skin fibrosis due to SSc

• Women postmenopausal or negative pre-treatment pregnancy test as well as a reliable method of contraception during study treatment and for at least 3 months after study treatment termination

• Signed informed consent

Exclusion Criteria:

• Severe PAH or interstitial lung disease (WHO class III and IV)

• Skin fibrosis and digital ulcers (DUs) due to conditions other than SSc

• Systolic BP < 85 mmHg

• Hemoglobin concentration < 75% of the lower limit of the normal range

• AST and/or ALT values greater than 3 times the upper limit of normal

• Moderate to severe hepatic impairment

• Severe malabsorption, severe organ failure or any life threatening condition

• Breast feeding

• Treatment with any of the following drugs: glibenclamide (glyburide), cyclosporine A, and tacrolimus 1 week prior to study participation

• Treatment with parenteral prostanoids 3 months prior to study participation

• Treatment with inhaled, subcutaneous or oral prostanoids 1 month prior to registration

• Systemic antibiotics to treat infection of DUs 2 weeks prior to study participation

• Current treatment with phosphodiesterase inhibitors such as sildenafil, except for intermittent treatment of male erectile dysfunction

• Patient with conditions that prevent compliance with the protocol or adhering to therapy

• Patient who received an investigational product within 1 month preceding screening

• Known hypersensitivity to bosentan or any of the excipients