Efficacy of Ambrisentan in Limited Scleroderma Patients in Improving Blood Flow to Hands or Feet (ambrisentan)

Evaluation of the Effect of Ambrisentan on Digital Microvascular Flow in Patients With Systemic Sclerosis Using Laser Doppler Perfusion Imaging

The purpose of this study is to investigate the effectiveness of a drug called ambrisentan, approved by the FDA for use in pulmonary hypertension (a condition where there is increased pressure in the right side of the heart) in scleroderma patients, to see if this medicine may be beneficial in relieving and/or preventing Raynaud's flares in you and other patients like you. This medicine may have some short-term and long-term benefits in persons with scleroderma

Study Overview

• Status: Completed
• Conditions: Ischemia
• Intervention / Treatment: Drug: ambrisentan

Detailed Description

Baseline screening-we will screen you with a baseline review of your history, medications and lab values and you will need to get blood drawn for hemoglobin level, liver function panel and blood pregnancy test for females in child bearing age group. Women are advised strongly to use 2 reliable forms of contraception while in this study unless you have had tubal ligation or intrauterine device placement.

You are advised to stop taking medications like nitrates (like nitroglycerin), calcium channel blockers (like nifedipine or amlodipine), angiotensin converting enzyme inhibitors (like lisinopril or enalapril or captopril), angiotensin receptor blockers (like valsartan or candesartan) or phosphodiesterase inhibitors (like Viagra or Revatio) at least 1 week prior to you coming for the first visit for the study and abstain from them during study period unless absolutely necessary.

Please avoid caffeine, smoking and over the counter cold remedies at least 2 days prior to the first visit and during the study period.

You will be asked to go to the Clinical Research Unit( CRU) located on M 51 in Cleveland Clinic main campus to partake in the study and will go back there for subsequent visits at 1 week and then at 12 weeks after having started the study.

This is a placebo-controlled randomized trial where 15 patients will get the active medication and the other 5 will get a placebo (pill with no active ingredient but not harmful to you in any way). This means you have a 3 in 4 (75%) chance of getting the active medication (ambrisentan) versus the placebo- both pills will look exactly the same. This process is called "randomization" and is similar to flipping a coin. The patients getting the active medication versus placebo will be randomly selected by the computer; the medications will be distributed by the central pharmacy and sent to the nurses on CRU and given to you on your first visit to the CRU. No one will know who received the active medication versus the placebo till the study ends and the data is analyzed.

Those getting the active medicine ambrisentan will initially get a dose of 5mg by mouth daily and then the dose will be increased to 10mg by mouth daily after 4 weeks if the medicine is well tolerated. This will be done by the computer for randomization/selection and the pharmacist for drug dispensing. If you experience any side effects, please contact us for further advice. You will be evaluated each visit by the nurses at weeks 0, 1 and 12 for any drug related problems. We will be monitoring the routine scheduled blood work results to make sure you do not develop any drug related problems which can be detected on blood work.

A machine called the 'Laser Doppler Perfusion Imaging' machine will be used at each of your visits to the CRU at weeks 0, 1 and 12. This machine uses simple laser beams and will scan the top part of your non-dominant hand (the left hand for most people) to measure the blood flow through the blood vessels there when your hand is at room temperature (around 77'F) and when it has been cooled to 50'F for 2 minutes with the help of a cold flask. This is a safe and simple technique and does not involve any radiation exposure.

You will also be asked to fill out 3 questionnaires at each of visits (week 0, 1 and 12) to the CRU-these have some simple questions regarding your degree of pain, severity of Raynaud's symptoms and the effect of scleroderma in your day-to-day functioning.

Please budget at least 1-2 hours for your initial visit (week 0) to the CRU and then 1 hour for your visits at 1 week and 12 weeks to the CRU.

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

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Nilanjana Bose, Md

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects should have limited scleroderma with disease duration <7 years and should satisfy American College of Rheumatology criteria for diagnosis.9;

• 10 Raynaud's phenomenon would be defined as episodic, bilateral, digital color changes (at least 2 out of 3 possible phases:

  • pallor, cyanosis, rubor),
  • provoked by cold or emotional stress.
• Subjects should be between 18 and 70 years of age and be able to give informed consent.

Exclusion Criteria:

• (a) current tobacco users,
• (b) advanced cardiopulmonary disease,
• (c) clinically unstable patient,
• (d) presence of active digital ulcers or prior history of digital ulcers which led to scarring or significant pitting of digits in the area of interest(presence of ulcers or pits would interfere with measurement of blood flow by LDPI),
• (e) pregnancy (class X in pregnancy) or unable to use two reliable forms of contraception during the study if patient is of child bearing age,
• (f) patients with moderate or severe hepatic impairment
• (g) hemoglobin values less than 10% of the lower limit of normal per laboratory standards
• (h) inability to discontinue vasodilator treatment including calcium channel blockers, nitrates, alpha blockers, PDE-5 inhibitors, ACE inhibitors and angiotensin receptor blockers at least one week prior to the study,
• (i) echocardiographic evidence of pulmonary arterial hypertension [estimated right ventricular systolic pressure <35 mm Hg],
• (j) based on section 7.3 of the full prescribing information booklet- patients on cyclosporine, rifampin or ritonavir should be excluded,
• (k) patients with diffuse disease,
• (l) disease duration > 7 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ambrisentan; drug arm use of ambrisentan in limited scleroderma patients with raynaud's to evaluate digital microvascular flow	Drug: ambrisentan; Subjects will receive ambrisentan 5 mg orally once daily or identical placebo pills for the first 4 weeks and then increased to ambrisentan 10mg once daily[if the lower dose is tolerated] or identical placebo pills for the rest of the study. They will be instructed to take the 5mg/pink pills for 4 weeks and then switch to 10mg /red pills unless they are having any drug related side effects or concerns. There will be no routine visit planned at 4 weeks to assess drug tolerance unless a complication arises. Adherence to treatment will be assessed by pill counting at each follow up visit. Follow up digital blood flow measurements will be obtained with LDPI at 1 week and at 3 months, where the same protocol (as that in the initial visit) will be followed.; Other Names: Letairis
Placebo Comparator: sugar pill; those getting sugar pill to evaluate if the active drug improves digital microvascular flow in limited scleroderma patients	Drug: ambrisentan; Subjects will receive ambrisentan 5 mg orally once daily or identical placebo pills for the first 4 weeks and then increased to ambrisentan 10mg once daily[if the lower dose is tolerated] or identical placebo pills for the rest of the study. They will be instructed to take the 5mg/pink pills for 4 weeks and then switch to 10mg /red pills unless they are having any drug related side effects or concerns. There will be no routine visit planned at 4 weeks to assess drug tolerance unless a complication arises. Adherence to treatment will be assessed by pill counting at each follow up visit. Follow up digital blood flow measurements will be obtained with LDPI at 1 week and at 3 months, where the same protocol (as that in the initial visit) will be followed.; Other Names: Letairis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Digital Micro-vascular Flow	Change in digital micro-vascular flow measured by LDPI in patients with Raynaud's phenomenon (RP) and digital ischemia secondary to SSc at 1 week and 12 weeks	Baseline and 12 weeks

Collaborators and Investigators

• Sponsor: Soumya Chatterjee
• Collaborators: Gilead Sciences
• Investigators: Principal Investigator: NILANJANA BOSE, MD, The Cleveland Clinic

Publications and helpful links

General Publications

• Bose N, Bena J, Chatterjee S. Evaluation of the effect of ambrisentan on digital microvascular flow in patients with systemic sclerosis using laser Doppler perfusion imaging: a 12-week randomized double-blind placebo controlled trial. Arthritis Res Ther. 2015 Mar 5;17(1):44. doi: 10.1186/s13075-015-0558-9.

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: February 19, 2010
• First Submitted That Met QC Criteria: February 19, 2010
• First Posted (Estimate): February 22, 2010

Study Record Updates

• Last Update Posted (Estimate): May 3, 2013
• Last Update Submitted That Met QC Criteria: March 22, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: Ambrisentan increases digital micro-vascular flow (measured by LDPI) in patients with Raynaud's phenomenon (RP) and digital ischemia secondary to SSc.
• Additional Relevant MeSH Terms: Pathologic Processes; Ischemia; Antihypertensive Agents; Ambrisentan
• Other Study ID Numbers: nbose2010