Effect of Bosentan on Skin Fibrosis in Patients With Systemic Sclerosis

NCT00318175 | Completed Phase 2

• 2 other identifiers: AMG 0022005-000798-23
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Systemic Scleroderma; Skin Fibrosis; Hand Functionality

Keywords

Systemic Scleroderma; Dermal Sclerosis; Bosentan; Endothelin Receptor Antagonist; Rodnan Skin Score

Outcome Measures

Primary Outcomes (1)

• Measurable reduction of skin thickening using 20 MHz-ultrasound and the Rodnan Skin Score after treatment with study medication over 24 weeks in patients with systemic sclerosis.

Secondary Outcomes (1)

• Effect of bosentan on hand functionality measured by SHAQ, UK-functional score, and fist closure as well as on nitrosylated serum protein levels in the plasma of patients with systemic scleroderma.

Interventions

Bosentan (Tracleer) DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Heinrich-Heine University, Duesseldorf: lead

Study Sites (1)

Heinrich-Heine-University of Duesseldorf, Department of Dermatology

Düsseldorf, North Rhine-Westphalia, 40225, Germany

Location

Related Publications (3)

• Korn JH, Mayes M, Matucci Cerinic M, Rainisio M, Pope J, Hachulla E, Rich E, Carpentier P, Molitor J, Seibold JR, Hsu V, Guillevin L, Chatterjee S, Peter HH, Coppock J, Herrick A, Merkel PA, Simms R, Denton CP, Furst D, Nguyen N, Gaitonde M, Black C. Digital ulcers in systemic sclerosis: prevention by treatment with bosentan, an oral endothelin receptor antagonist. Arthritis Rheum. 2004 Dec;50(12):3985-93. doi: 10.1002/art.20676.

  PMID: 15593188 BACKGROUND

• Hachulla E, Coghlan JG. A new era in the management of pulmonary arterial hypertension related to scleroderma: endothelin receptor antagonism. Ann Rheum Dis. 2004 Sep;63(9):1009-14. doi: 10.1136/ard.2003.017673.

  PMID: 15308510 BACKGROUND

• Snyder MJ, Jacobs MR, Grau RG, Wilkes DS, Knox KS. Resolution of severe digital ulceration during a course of Bosentan therapy. Ann Intern Med. 2005 May 3;142(9):802-3. doi: 10.7326/0003-4819-142-9-200505030-00029. No abstract available.

  PMID: 15867420 BACKGROUND

MeSH Terms

Conditions

Scleroderma, Systemic

Interventions

Bosentan

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Annegret Kuhn, MD

  Heinrich-Heine-University of Duesseldorf, Department of Dermatology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: April 24, 2006
• First Posted: April 26, 2006
• Study Start: June 1, 2006
• Study Completion: May 1, 2007
• Last Updated: September 10, 2007

Record last verified: 2007-09

Locations

DE (1)