Clinical Trial: A Trial of Tadalafil in Interstitial Lung Disease of Scleroderma

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Double Blind Randomized Control Trial of Tadalafil in Interstitial Lung Disease of Scleroderma

Brief Summary:

Systemic sclerosis (SSc, scleroderma) is a multisystem autoimmune rheumatic disease that causes inflammation, vascular damage and fibrosis. Besides involvement of skin, fibrosis also affects lung and heart. Although advances in understanding in pathophysiology and use of immunosuppressive therapy has brought significant improvement in outcome of other autoimmune diseases, scleroderma still remains as a disease with high mortality and 10 yr survival rate has improved only from 54% to 66% during last 25 years1. The frequency of deaths due to renal crisis significantly decreased (mainly due to effectiveness of ACE Inhibitors), from 42% to 6% of scleroderma-related deaths (p 0.001), whereas the proportion of patients with scleroderma who died of pulmonary fibrosis increased (due to lack of significant treatment) from 6% to 33% (p 0.001). However, presently, trials with immunosuppressive drugs including cyclophosphamide and other targeted molecules like Bosentan and Imatinib mesylate have shown very modest results at the best and given the risk of toxicity. The investigators have conducted three clinical trials with PDE5 inhibitor Tadalafil in the refractory Raynaud's phenomenon (RP) in SSc over last 3 years and had found good response in RP, healing of digital ulcers, prevention of new digital ulcers and also observed improvement in skin tightening, endothelial dysfunction and improvement of quality of life. The investigators therefore hypothesize that tadalafil may have an efficacy in improving the ILD of SSc.

The investigators therefore design this double-blind, randomized, placebo-controlled trial of oral Tadalafil (20 mg alternate day) in patients with SSc having ILD. Patients will be randomly assigned in a 1:1 ratio to receive either Tadalafil or matched placebo and will be followed up for 6 months. Prednisolone (if required for indications other than ILD) wi

Detailed Summary:

Systemic sclerosis (SSc, scleroderma) is a multisystem autoimmune rheumatic disease that causes inflammation, vascular damage and fibrosis. Besides involvement of skin, fibrosis also affects many internal organ involving blood vessel, lungs, heart, kidney etc. Although advances in understanding in pathophysiology and use of immunosuppressive therapy has brought significant improvement in outcome of other autoimmune diseases, scleroderma still remains as a disease with high mortality and 10 yr survival rate has improved only from 54% to 66% during last 25 years1. But there is a significant change in pattern of cause of mortality over these years. The frequency of deaths due to renal crisis significantly decreased (mainly due to effectiveness of ACE Inhibitors), from 42% to 6% of scleroderma-related deaths (p 0.001), whereas the proportion of patients with scleroderma who died of pulmonary fibrosis increased (due to lack of significant treatment) from 6% to 33% (p 0.001). The frequency of pulmonary hypertension, independent of PF, also significantly increased during this time period (p<0.05)1. Presently PAH and interstitial lung disease accounts for majority of scleroderma related deaths. This emphasizes the need of novel therapies for interstitial lung disease in scleroderma, in order to improve the mortality and morbidity outcome of these patients.

The fibrosis of the skin and internal organs in SSc is believed to be caused by the transition of quiescent fibroblasts to activated myofibroblasts, which characteristically overproduce dermal fibrillar collagen (type I, III, V), collagen-modifying enzymes and other extracellular matrix (ECM) components2. One of the major cytokines involved in this process is transforming growth factor TGF β1 3. TGF-β is normally secreted as a latent complex, which is required to be activated in extrac
Sponsor: Sanjay Gandhi Postgraduate Institute of Medical Sciences

Current Primary Outcome: Change in FVC (expressed as a percentage of the predicted value) [ Time Frame: 6 months ]

Original Primary Outcome: To assess the change in FVC (expressed as a percentage of the predicted value) [ Time Frame: 6 months ]

Current Secondary Outcome:

• Improvement in dyspnoea (as measured by Mehler dyspnoea index) [ Time Frame: 6 months ]
  To assess the improvement in dyspnoea (as measured by Mehler dyspnoea index) at the end of 6 month
• Improvement in 6 min walk test [ Time Frame: 6 months ]
  To assess improvement in 6 min walk test at the end of 6 months
• change in DLCO [ Time Frame: 6 months ]
  To assess the change in DLCO from baseline values at the end of 6 months
• change in total lung capacity [ Time Frame: 6 months ]
  To assess the change in total lung capacity from baseline values at the end of 6 months
• change in the disability index of the Health Assessment Questionnaire (S HAQ) [ Time Frame: 6 months ]
  To assess the change in the disability index of the Health Assessment Questionnaire (S HAQ) at 6 months from baseline
• change in the Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36)scores [ Time Frame: 6 months ]
  To assess the change in the Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36) from baseline to end of 6 months

Original Secondary Outcome:

• To assess the improvement in dyspnoea (as measured by Mehler dyspnoea index) [ Time Frame: 6 months ]
  To assess the improvement in dyspnoea (as measured by Mehler dyspnoea index) at the end of 6 month
• To assess improvement in 6 min walk test [ Time Frame: 6 months ]
  To assess improvement in 6 min walk test at the end of 6 months
• change in DLCO [ Time Frame: 6 months ]
  To assess the change in DLCO from baseline values at the end of 6 months
• change in total lung capacity [ Time Frame: 6 months ]
  To assess the change in total lung capacity from baseline values at the end of 6 months
• change in the disability index of the Health Assessment Questionnaire (S HAQ) [ Time Frame: 6 months ]
  To assess the change in the disability index of the Health Assessment Questionnaire (S HAQ) at 6 months from baseline
• change in the Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36)scores [ Time Frame: 6 months ]
  To assess the change in the Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36) from baseline to end of 6 months

Information By: Sanjay Gandhi Postgraduate Institute of Medical Sciences

Dates:
Date Received: March 11, 2012
Date Started: March 2012
Date Completion:
Last Updated: April 20, 2015
Last Verified: April 2015