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

Sponsor

Sanjay Gandhi Postgraduate Institute of Medical Sciences (Other)

Overall Status

Completed

CT.gov ID

NCT01117298

Collaborator

Institute of Postgraduate Medical Education and Research (Other), Postgraduate Institute of Medical Education and Research (Other), Army Research and Referral hospital (Other)

Enrollment

Locations

Arms

5.9

Duration (Months)

16.5

Patients Per Site

2.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Raynaud's Phenomenon Digital Ulcers Scleroderma	Drug: Tadalafil Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

66 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Nov 1, 2009

Actual Primary Completion Date :

Apr 1, 2010

Actual Study Completion Date :

May 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tadalafil	Drug: Tadalafil Tab Tadalafil, 20 mg alternate day for 8 weeks Other Names: Tadalis
Placebo Comparator: Placebo	Drug: Placebo Tab Placebo every alternate day for 8 weeks

Arm

Intervention/Treatment

Experimental: Tadalafil

Drug: Tadalafil

Tab Tadalafil, 20 mg alternate day for 8 weeks

Other Names:

Tadalis

Placebo Comparator: Placebo

Drug: Placebo

Tab Placebo every alternate day for 8 weeks

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Clinical Immunology, Army R&R hospital	New Delhi	ND	India
2	Medicine Unit II, PGIMER	Chandigarh	Punjab	India
3	Department of Immunology, SGPGIMS	Lucknow	UP	India	226014
4	Immunology Rheumatology Unit, IPGMER	Kolkatta	WB	India