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Systemic SclerodermaPhase 2NCT00318175

Effect of Bosentan on Skin Fibrosis in Patients With Systemic Sclerosis

A Phase 2 study testing Bosentan (Tracleer) in people with Systemic Scleroderma and Skin Fibrosis, run by Heinrich-Heine University, Duesseldorf at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Bosentan (Tracleer)
How many people
10 participants
Where
1 siteGermany
Study dates
Jun 2006to May 2007
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 16Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Heinrich-Heine-University of Duesseldorf, Department of Dermatology

    Düsseldorf, North Rhine-Westphalia, 40225

Other trials in Germany

About this study

Official title: Study to Assess the Effect of Bosentan on the Treatment of Skin Fibrosis in Patients With Systemic Sclerosis (BTSF)

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.

Read the detailed description

Systemic sclerosis (SSc) is a polymorphic disorder with an unknown cause characterized by fibrosis of the skin, blood vessels, and visceral organs. The degree of skin involvement is a very important outcome measure in patients with this disease. The pathogenesis of SSc involves immunologic mechanisms, vascular damage, and excessive accumulation of extracellular matrix component in the skin. One reason for these changes is meant to be an increased release of endothelin-1, a peptide which has vasoconstrictor effects and possesses mitogenic activity on cultured vascular smooth muscle cells and fibroblasts, cell types that are involved in SSc pathogenesis. Interestingly, endothelin-1 levels are raised in patients with SSc and Raynaud´s disease, particularly, in the subset of patients with diffuse cutaneous SSc who have widespread dermal sclerosis. However, skin fibrosis in SSc is a poorly studied, rare condition for which there are no approved therapies. Bosentan is a dual endothelin receptor antagonist, that competes with the binding of endothelin-1 to both receptors (ET-A and AT-B). It was recently shown to be effective in the treatment of idiopathic as well as pulmonary arterial hypertension (PAH) in SSc, but it has also been proved in two multicenter randomized prospective placebo-controlled double-blind studies in Europe and the US (RAPIDS-1 and RAPIDS-2) that there is a beneficial effect of bosentan in preventing digital ulcers in these patients. Furthermore,it has been suggested that bosentan has also a positive effect on skin fibrosis. In this study, skin fibrosis will be measured using 20-MHz-ultrasound, the Rodnan Skin Score, and investigation of the fist closure of each patient during treatment with bosentan over 24 weeks.

Being tested
Bosentan (Tracleer)
Keywords
Systemic Scleroderma, Dermal Sclerosis, Bosentan, Endothelin Receptor Antagonist, Rodnan Skin Score
Medical subject headings
Scleroderma, Systemic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Bosentan (Tracleer)Drug

What is being measured

The primary outcome is the main question the study is designed to answer.

  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)

  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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Apr 2006 (estimated)
  2. Study startJun 2006
  3. Study completionMay 2007

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00318175
Sponsor's protocol ID
AMG 002
Other IDs
2005-000798-23, 2005
Status last verified
Sep 2007
First submitted
24 Apr 2006
Last updated
10 Sep 2007
Results posted
No

Publications

  • 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.

    PubMed 15593188

  • 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.

    PubMed 15308510

  • 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.

    PubMed 15867420

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bosentan (Tracleer) in people with Systemic Scleroderma and Skin Fibrosis, run by Heinrich-Heine University, Duesseldorf at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Sep 2007. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00318175, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2007.

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