A Study to Evaluate the Efficacy of an Oral Medication in the Treatment and Prevention of Digital Ulcers in Patients With Systemic Sclerosis (Scleroderma).

A Pilot Study to Evaluate the Efficacy of Ambrisentan in the Treatment and Prevention of Digital Ulcers in Patients With Systemic Sclerosis.

This is a research study of an investigational drug called ambrisentan (Letairis) in the treatment and prevention of digital ulcers in patients with systemic sclerosis.

Study Overview

• Status: Completed
• Conditions: Scleroderma, Systemic; n Ulcer
• Intervention / Treatment: Drug: Ambrisentan

Detailed Description

Ambrisentan is an endothelin blocker approved for the treatment of pulmonary arterial hypertension. Patients with systemic sclerosis can have damage to their blood vessels, resulting in increased levels of endothelin in their bloodstream that then causes decreased blood flow to the digits. This can result in very painful digital ulcers. We hope to learn whether blocking the action of endothelin with ambrisentan will be helpful in the treatment and prevention of digital ulcers in patients with systemic sclerosis. This therapy is not approved for the treatment of systemic sclerosis, but this study will help us learn whether ambrisentan is safe and effective in the treatment and prevention of digital ulcers in patients with systemic sclerosis.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of limited or diffuse systemic sclerosis (SSc) according to American College of Rheumatology or LeRoy criteria
• Age greater than 18 years of age
• At least one digital ulcer located on the volar or lateral surface at or distal to the proximal interphalangeal joints
• At least one new DU that developed within 12 weeks prior to screening
• Vasodilator therapies, including calcium channel blockers, alpha-1-antagonists, ACE-inhibitors, nitroglycerin, and angiotensin receptor blockers, are permitted as long as the doses are stable for 2 weeks prior to screening and throughout the study
• Treatment with omeprazole or other proton pump inhibitors must be stable for 2 weeks prior to screening and throughout the study

Exclusion Criteria:

• Patients with pulmonary arterial hypertension, NYHA Class III or IV
• Patients who are hemodynamically unstable, or have acute renal, cardiac or pulmonary failure
• Concurrent malignancy except non-melanoma skin cancers
• Patients who have required systemic antibiotics for infected digital ulcers within 2 weeks of screening
• Patients receiving phosphodiesterase-5 inhibitors, endothelin receptor antagonists, or prostanoids within 4 weeks of screening
• Patients receiving cyclosporine within 6 weeks of screening
• Patients who have participated in any investigational study within 30 days of screening
• Pregnant or nursing women
• Patients with a history of drug or alcohol abuse within 6 months of screening
• History of hepatitis B, hepatitis C, or HIV infection
• Any medical condition that, in the opinion of the investigator, might interfere with the subject's participation in the study or poses an added risk for the subject
• Inability to comply with study and follow-up procedures
• Transaminase elevation > 3X the upper limit of normal at screening
• Hemoglobin less than 8.5 g/dL
• Platelet count less than 100 X 109/L
• White blood cell count less than 3.0 X 109/L
• Serum creatinine less than 2.0 mg/dL

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active; Ambrisentan	Drug: Ambrisentan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
New Digital Ulcers (DU) 4 Weeks Prior to Week 24	The number of new digital ulcers (DU) that have developed in the preceding 4 weeks assessed at week 24 from baseline.	4 weeks prior to week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
New DU 4 Weeks Prior to Week 12	The number of new DU that have developed in the preceding 4 weeks assessed at week 12 from baseline.	4 weeks prior to week 12
Subjects Experiencing Complete (Total Reepithelialization) Healing of All Baseline DU at Week 12.		12 weeks
Subjects Experiencing Complete Healing of > 50% of the Number of Baseline DU at Week 12.		12 weeks
Change in the Scleroderma Health Assessment Questionnaire (SHAQ) at Week 24 Compared With Baseline.	Range is 0-3 with 0 meaning the least amount of disability and 3 the greatest of disability.	24 weeks

Collaborators and Investigators

• Sponsor: Stanford University

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: July 28, 2008
• First Submitted That Met QC Criteria: July 28, 2008
• First Posted (Estimate): July 30, 2008

Study Record Updates

• Last Update Posted (Actual): March 31, 2017
• Last Update Submitted That Met QC Criteria: March 1, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Connective Tissue Diseases; Ulcer; Scleroderma, Systemic; Scleroderma, Diffuse; Antihypertensive Agents; Ambrisentan
• Other Study ID Numbers: SU-07222008-1265; IRB Protocol # 14409