A Trial of Tadalafil in Interstitial Lung Disease of Scleroderma

This study is currently recruiting participants.
Verified December 2012 by Sanjay Gandhi Postgraduate Institute of Medical Sciences
Sponsor:
Information provided by (Responsible Party):
Vikas Agarwal, Sanjay Gandhi Postgraduate Institute of Medical Sciences
ClinicalTrials.gov Identifier:
NCT01553981
First received: March 11, 2012
Last updated: December 11, 2012
Last verified: December 2012
  Purpose

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) will be allowed up to 10 mg/d in all patients. Patient/s requiring more than 10 mg/d of prednisolone or equivalent dose of steroid will be excluded from the study. Patients who will fail on therapy during the study will be excluded from the study and will be asked to choose any therapeutic option from the rescue protocol.

Patients with FVC ≤ 70% predicted or DLCO ≤ 70 % of predicted, Evidence of ILD on HRCT will be enrolled. The primary objective of the study will be the change in FVC (expressed as a percentage of the predicted value) from baseline values at the end of 6-months of treatment. The secondary objectives will be improvement in dyspnea, improvement in 6 min walk distance, change in DLCO, change in total lung capacity, change in the disability index of the Health Assessment Questionnaire (S HAQ), and change quality of life (SF-36), levels of NT pro-BNP and fibrosis markers.


Condition Intervention Phase
Lung Diseases, Interstitial
Drug: Tadalafil
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double Blind Randomized Control Trial of Tadalafil in Interstitial Lung Disease of Scleroderma

Resource links provided by NLM:


Further study details as provided by Sanjay Gandhi Postgraduate Institute of Medical Sciences:

Primary Outcome Measures:
  • Change in FVC (expressed as a percentage of the predicted value) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To assess the change in FVC (expressed as a percentage of the predicted value) from baseline values at the end of 6 months


Secondary Outcome Measures:
  • Improvement in dyspnoea (as measured by Mehler dyspnoea index) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    To assess improvement in 6 min walk test at the end of 6 months

  • change in DLCO [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To assess the change in DLCO from baseline values at the end of 6 months

  • change in total lung capacity [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 36
Study Start Date: March 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Tadalafil
Tablet Tadalafil 20 mg every alternate day
Drug: Tadalafil
Tab. Tadalafil 20 mg every other day for 6 months
Placebo Comparator: Placebo
Tablet Placebo every alternate day
Drug: Placebo
Shape , size, color and odor matched Tab. of inert material every other day for 6 months

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Fulfillment of the criteria for systemic sclerosis (SSc) by American College or Rheumatology (ACR) criteria (Subcommittee for Scleroderma Criteria, 1980)
  2. Forced vital capacity (FVC) ≤ 70% predicted.
  3. DLCO ≤ 70 % of predicted

3. Presence of dyspnea on exertion (grade 2 on the Magnitude of Task component of the Mahler Modified Dyspnea Index) 4. Evidence of ILD on HRCT

Exclusion Criteria:

  1. Those that cannot perform PFT or 6 min walk test
  2. High dose prednisolone (1 mg/kg) or cyclophosphamide (> 500 mg) or MMF (> 500mg/d) or (azathioprine > 1 mg/kg) for more than 4 weeks anytime within previous 6 months
  3. SBP < 90 mmHg or history of orthostatic hypotension
  4. Current smokers
  5. Women who are pregnant or lactating
  6. Those receiving nitrates, alpha blockers, or both, other phosphodiesterase inhibitors
  7. Current use of captopril (because of sulfhydryl group). If ACE- inhibitors are indicated, an ACE-inhibitor other than captopril should be used.
  8. Serum creatinine ≥ 2.0 mg/dl.
  9. Obstructive lung disease (FEV1/FVC ratio < 0.6)
  10. Prostacyclins or endothelin antagonists or who had received any investigational drug within the prior month
  11. Acute coronary or cerebrovascular event within 3 months
  12. Evidence of malignancy
  13. Peptic ulcer
  14. Hepatic dysfunction.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01553981

Contacts
Contact: Vikas Agarwal, MD, DM 915222494318 vikasagr@sgpgi.ac.in
Contact: Jyoti R Parida, MD 918004904399 drjyoti@sgpgi.ac.in

Locations
India
SGPGIMS Recruiting
Lucknow, UP, India, 226014
Contact: Vikas Agarwal, MD, DM    915222494318    vikasagr@sgpgi.ac.in   
Contact: Jyoti R Parida, MD    918004904399    drjyoti@sgpgi.ac.in   
Principal Investigator: Vikas Agarwal, MD, DM         
Sponsors and Collaborators
Sanjay Gandhi Postgraduate Institute of Medical Sciences
Investigators
Principal Investigator: Vikas Agarwal, MD, DM SGPGIMS
  More Information

No publications provided

Responsible Party: Vikas Agarwal, Additional Professor, Sanjay Gandhi Postgraduate Institute of Medical Sciences
ClinicalTrials.gov Identifier: NCT01553981     History of Changes
Other Study ID Numbers: PGI/BE/06/2012
Study First Received: March 11, 2012
Last Updated: December 11, 2012
Health Authority: India: Institutional Review Board

Keywords provided by Sanjay Gandhi Postgraduate Institute of Medical Sciences:
Interstitial lung disease
Scleroderma

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Interstitial
Scleroderma, Systemic
Scleroderma, Diffuse
Connective Tissue Diseases
Skin Diseases
Respiratory Tract Diseases
Tadalafil
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014