A Randomized Control Trial to Assess the Efficacy of Tadalafil in Raynaud's Phenomenon in Scleroderma

Study Overview
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Brief Summary
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Raynaud's phenomenon (RP) associated with scleroderma is a difficult problem to treat. Many patients develop ischemic digital ulcers due to severe RP that causes considerable morbidity and adversely affects the quality of life. In an earlier study, we have observed marked improvement in RP attacks and rapid healing of digital ulcers following therapy with phosphodiesterase V inhibitor, Tadalafil. In the present multicentric study we aim to study the efficacy of Tadalafil in patients continuing to have RP attacks despite using at least one or more vasodilators.

Official Title
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A Randomized Control Trial to Assess the Efficacy of Tadalafil in Raynaud's Phenomenon in Scleroderma: A Double Blind, Parallel Group, Multicentric Study

Conditions
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Raynaud's Phenomenon, Digital Ulcers, Scleroderma

Intervention / Treatment
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* Drug: Tadalafil
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects between the ages of 18 years and 65 years will be selected for the study if they have a clinical diagnosis of Raynaud's phenomenon secondary to systemic sclerosis (scleroderma) despite being on vasodilator therapy. Raynaud's phenomenon is defined as a history of cold sensitivity associated with colour changes of cyanosis or pallor. Patients with a history of at least 4 attacks per week during two-week pre-trial period even with treatment with other vasodilators will be recruited. Patients fulfilling the diagnostic criteria of scleroderma (as per American College of Rheumatology criteria) or having presence of at least 3 of the 5 features of the CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias)will be invited to participate in the study. Exclusion Criteria: Patients with: Symptomatic orthostatic hypotension, Evidence of current malignancy, History of sympathectomy, Upper extremity deep vein thrombosis or lymphedema within 3 months, Recent surgical procedure requiring general anesthesia, Acute Myocardial Infarction, unstable angina, strokes and transient ischemic attacks within the past three months, Smoking, Use of any investigational drug within 30 days of the study sessions, Use of medications that might interfere with tadalafil like nitrates and alpha adrenergic blockers that have vasoactive effects, and patients taking potent inhibitors of CYP3A4 such as ritonavir, ketoconazole, and itraconazole, erythromycin, itraconazole, and grapefruit juice, Patients taking alcohol, Patients with bleeding disorders Significant active peptic ulceration, Current pregnancy, Current breast-feeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tadalafil<br> | Drug: Tadalafil<br>* Tab Tadalafil, 20 mg alternate day for 8 weeks<br>* Other names: Tadalis;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Tab Placebo every alternate day for 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily frequency, duration and severity of Raynaud's phenomenon |  | Baseline and 8 weeks | 
| Appearance or healing of digital ulcers |  | Baseline and 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in health assessment questionnaire |  | Baseline and 8 weeks | 
| Improvement in scleroderma specific health assessment questionnaire |  | Baseline and 8 weeks | 
| Improvement in quality of life |  | Baseline and 8 weeks | 
| Improvement in biomarkers of endothelial dysfunction |  | Baseline and 8 weeks | 
| Improvement in flow mediated dilatation |  | Baseline and 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Raynaud's phenomenon, ischemic ulcers, digital ulcers, digital infarcts, gangrene, vasodilators, endothelial dysfunction, scleroderma