Clinical trial NCT01117298: A Randomized Control Trial to Assess the Efficacy of Tadalafil in Raynaud's Phenomenon in Scleroderma
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Raynaud's Phenomenon
Digital Ulcers
Scleroderma
Keywords: Raynaud's phenomenon
ischemic ulcers
digital ulcers
digital infarcts
gangrene
vasodilators
endothelial dysfunction
scleroderma
Lead sponsor: Sanjay Gandhi Postgraduate Institute of Medical Sciences
Sponsor class: OTHER_GOV
Collaborators: name: Institute of Postgraduate Medical Education and Research
name: Post Graduate Institute of Medical Education and Research, Chandigarh
name: Army Hospital Research And Referral, India
First posted: 2010-05-05
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Daily frequency, duration and severity of Raynaud's phenomenon
timeFrame: Baseline and 8 weeks
measure: Appearance or healing of digital ulcers
timeFrame: Baseline and 8 weeks
Secondary outcomes:
measure: Improvement in health assessment questionnaire
timeFrame: Baseline and 8 weeks
measure: Improvement in scleroderma specific health assessment questionnaire
timeFrame: Baseline and 8 weeks
measure: Improvement in quality of life
timeFrame: Baseline and 8 weeks
measure: Improvement in biomarkers of endothelial dysfunction
timeFrame: Baseline and 8 weeks
measure: Improvement in flow mediated dilatation
timeFrame: Baseline and 8 weeks
Other outcomes:
Locations:
city: New Delhi
country: India
facility: Department of Clinical Immunology, Army R&R hospital
state: ND
city: Chandigarh
country: India
facility: Medicine Unit II, PGIMER
state: Punjab
city: Lucknow
country: India
facility: Department of Immunology, SGPGIMS
state: UP
city: Kolkatta
country: India
facility: Immunology Rheumatology Unit, IPGMER
state: WB
Study officials:
affiliation: IPGMER, Kolkatta
name: Parasar Ghosh, MD, DM
role: PRINCIPAL_INVESTIGATOR
affiliation: PGIMER, Chandigarh
name: Aman Sharma, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Army R&R Hospital, New Delhi
name: Darshan S Bhakuni, MD
role: PRINCIPAL_INVESTIGATOR
References: