Clinical trial NCT01072669
Conditions: Ischemia
Keywords: Ambrisentan increases digital micro-vascular flow (measured by LDPI) in patients with Raynaud's phenomenon (RP) and digital ischemia secondary to SSc.
Sponsor: Soumya Chatterjee
Start date: 2010-02-01; Completion date: 2010-12-01
Enrollment: 20 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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

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.

Arms: arm 1: drug arm

use of ambrisentan in limited scleroderma patients with raynaud's to evaluate digital microvascular flow arm 2: those getting sugar pill to evaluate if the active drug improves digital microvascular flow in limited scleroderma patients
Interventions: intervention 1: ambrisentan
Intervention descriptions: intervention 1: 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.

Protocol documents: