Ignite Creation Date:
2024-05-05 @ 7:13 PM
Last Modification Date:
2024-10-26 @ 9:45 AM
Study NCT ID:
NCT00626665
Status:
COMPLETED
Last Update Posted:
2013-03-22
First Post:
2008-02-21
Brief Title:
Randomised Control Trial to Assess the Efficacy of Tadalafil in Raynauds Phenomenon in Scleroderma
Sponsor:
Sanjay Gandhi Postgraduate Institute of Medical Sciences
Organization:
Sanjay Gandhi Postgraduate Institute of Medical Sciences
Study Overview
Official Title:
Randomised Control Trial to Assess the Efficacy of Tadalafil in Raynauds Phenomenon in Scleroderma
Status:
COMPLETED
Status Verified Date:
2013-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
In this double-blinded placebo-controlled fixed-dose study patients will be randomly assigned to take placebo or 20 mg tadalafil thrice weekly for 6 weeks After 6 weeks a wash out period of 2 week will be observed and then the two groups will be switched over to receive the other drug We planned a priori to include 20 patients The concomitant medication for treatment of rheumatic disease remained unchanged during the whole study Patient will undergo clinical and lab evaluation for organ damage for kidney and lungs ECHO heart will be done at base line to assess the PAH and LV function and repeated at the end of the study Blood pressure will be recorded at each visit A physician unaware of the treatment group will record skin score and appearance of new cutaneous ulcers The primary outcome variables will be frequency and duration of Raynauds attacks evolution of trophic digital lesions and change in flow mediated dilatation of the brachial artery Flow mediated dilatation of the brachial artery will be done at baseline 6 and 12 weeks
Detailed Description:
Introduction Raynauds syndrome which was first described by Maurice Raynaud in 1862 is defined as episodic cold or emotional stress-triggered ischemic vasospasms of the digital arteries and precapillary arterioles This phenomenon affects 95 of the systemic sclerosis SScl patients and may lead to superficial ulcerations and in severe cases can even result in deep tissue necrosis with gangrene Raynauds phenomenon RP is symptom of a generalised vasculopathy in SScl which eventually leads to a fibroproliferative arteriopathy Pulmonary artery hypertension is one of many serious sequelae of this process Nonpharmacological therapy includes avoidance of cold temperatures emotional stress and smoking Pharmacological therapy with vasodilators such as calcium channel blockers alpha adrenergic receptor blockers or angiotensin II receptor antagonists and other agents has been used Effects of treatments however are often inadequate1 Sildenafil is a selective inhibitor of cGMP specific phosphodiesterase type 5 Besides its established effect in erectile dysfunction sildenafil provides cGMP-dependent microvascular and macrovascular dilation and furthermore were recently shown to exhibit antiproliferative effects2 There are a few studies in the literature on the efficacy of sildenafil in Raynauds disease3-5 It has been shown by these studies and a few case reports that sildenafil may be useful in RP The limitation of sildenafil is its short t12 4 hours Tadalafil is more selective and longer acting 17 hours analogue of sildenafil6 These PDE 5 inhibitors have been shown to improve endothelial function in diabetic subjects and cold induced vasospasm7 It is a well known fact that endothelial dysfunction is one of the major pathogenetic mechanisms in scleroderma8 There has been no randomised control trial on the efficacy of tadalafil in RP There is one study that had shown beneficial effect of Tadalafil in cold induced vasoconstriction in pateints with Raynauds phenomenon9 So we designed this study to assess the effect of tadalafil on Raynauds phenomenon and endothelial dysfunction in scleroderma We hypothesise that the tadalafil improves the Raynauds phenomenon and endothelial dysfunction in scleroderma patients and can act as a disease-modifying agent
Patients with systemic scleroderma will be enrolled
Study Protocol In this double-blinded placebo-controlled fixed-dose study patients will be randomly assigned to take placebo or 20 mg tadalafil thrice weekly for 6 weeks After 6 weeks a wash out period of 2 week will be observed and then the two groups will be switched over to receive the other drug We planned a priori to include 30 patients The concomitant medication for treatment of rheumatic disease remained unchanged during the whole study Patient will undergo clinical and lab evaluation for organ damage for kidney and lungs ECHO heart will be done at base line to assess the PAH and LV function and repeated at the end of the study Blood pressure will be recorded at each visit A physician unaware of the treatment group will record skin score and appearance of new cutaneous ulcers The primary outcome variables will be frequency and duration of Raynauds attacks evolution of trophic digital lesions and change in flow mediated dilatation of the brachial artery Flow mediated dilatation of the brachial artery will be done at baseline 6 and 12 weeks
Clinical Evaluation Symptoms of Raynauds phenomenon will be assessed by diary cards When an attack occurred patients immediately recorded the event and its duration in the diary At the end of each day patients gave an overall estimation of the last 24 hours using a 10-point Raynauds Condition Score 0 points - subject felt not handicapped by Raynauds attacks 10 points - subject felt extremely handicapped validated as described elsewhere Local Temperature will be recorded in a separate column in the diary daily
Assessment of cutaneous digital tip ulcers infarcts
The number and position of cutaneous digital tip ulcers or infarcts on any finger will be recorded Data on both ulcers and infarcts will be collected
Health Assessment Questionnaire HAQ
The HAQ is a self-administered instrument that measures physical disability in 8 domains of function dressinggrooming arising eating walking hygiene reach grip and activity A visual analog scale VAS for pain is also part of the HAQ The results for the 8 subscales the composite disability score and the pain measurement are each reported on a 0-3 scale The HAQ has been used extensively in studies of rheumatoid arthritis and has also been validated in patients with scleroderma Levels of circulating soluble markers of endothelial cell function including soluble isoforms of endothelin 1 ET-1 von Willebrand factor vWF and procollagen type I N-terminal propeptide PINP will be measured at 0 and 12 weeks Statistics Students T test will be applied to the continuous variables whereas chi square test will be applied to categorical variables
From an analysis of the daily record sheets the Following will be calculated i the total average daily duration of the attacks TADDA obtained by dividing the total duration in min of attacks during a given three -week interval observation period by the number of diary days ii the average duration of a single attack ADSA by dividing the overall duration by the number of attacks during the observation period iii the average daily frequency of the attacks ADFA by dividing the total number of attacks during the interval considered 3 weeks by the number of diary days and iv the severity of the attacks measured on a visual analogical scale this will be designated the Raynauds condition score RCS and will be calculated as the arithmetic average of the daily scores during the interval considered 3weeks
Patients with systemic scleroderma will be enrolled
Study Protocol In this double-blinded placebo-controlled fixed-dose study patients will be randomly assigned to take placebo or 20 mg tadalafil thrice weekly for 6 weeks After 6 weeks a wash out period of 2 week will be observed and then the two groups will be switched over to receive the other drug We planned a priori to include 30 patients The concomitant medication for treatment of rheumatic disease remained unchanged during the whole study Patient will undergo clinical and lab evaluation for organ damage for kidney and lungs ECHO heart will be done at base line to assess the PAH and LV function and repeated at the end of the study Blood pressure will be recorded at each visit A physician unaware of the treatment group will record skin score and appearance of new cutaneous ulcers The primary outcome variables will be frequency and duration of Raynauds attacks evolution of trophic digital lesions and change in flow mediated dilatation of the brachial artery Flow mediated dilatation of the brachial artery will be done at baseline 6 and 12 weeks
Clinical Evaluation Symptoms of Raynauds phenomenon will be assessed by diary cards When an attack occurred patients immediately recorded the event and its duration in the diary At the end of each day patients gave an overall estimation of the last 24 hours using a 10-point Raynauds Condition Score 0 points - subject felt not handicapped by Raynauds attacks 10 points - subject felt extremely handicapped validated as described elsewhere Local Temperature will be recorded in a separate column in the diary daily
Assessment of cutaneous digital tip ulcers infarcts
The number and position of cutaneous digital tip ulcers or infarcts on any finger will be recorded Data on both ulcers and infarcts will be collected
Health Assessment Questionnaire HAQ
The HAQ is a self-administered instrument that measures physical disability in 8 domains of function dressinggrooming arising eating walking hygiene reach grip and activity A visual analog scale VAS for pain is also part of the HAQ The results for the 8 subscales the composite disability score and the pain measurement are each reported on a 0-3 scale The HAQ has been used extensively in studies of rheumatoid arthritis and has also been validated in patients with scleroderma Levels of circulating soluble markers of endothelial cell function including soluble isoforms of endothelin 1 ET-1 von Willebrand factor vWF and procollagen type I N-terminal propeptide PINP will be measured at 0 and 12 weeks Statistics Students T test will be applied to the continuous variables whereas chi square test will be applied to categorical variables
From an analysis of the daily record sheets the Following will be calculated i the total average daily duration of the attacks TADDA obtained by dividing the total duration in min of attacks during a given three -week interval observation period by the number of diary days ii the average duration of a single attack ADSA by dividing the overall duration by the number of attacks during the observation period iii the average daily frequency of the attacks ADFA by dividing the total number of attacks during the interval considered 3 weeks by the number of diary days and iv the severity of the attacks measured on a visual analogical scale this will be designated the Raynauds condition score RCS and will be calculated as the arithmetic average of the daily scores during the interval considered 3weeks
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None