Scleroderma Lung Disease (SLS)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Maureen Mayes, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier:
NCT00004563
First received: February 9, 2000
Last updated: March 5, 2015
Last verified: March 2015
  Purpose

To evaluate the efficacy and safety of cyclophosphamide versus placebo for the prevention and progression of symptomatic pulmonary disease in patients with systemic sclerosis.


Condition Intervention Phase
Lung Diseases
Pulmonary Fibrosis
Systemic Scleroderma
Scleroderma, Systemic
Drug: Cyclophosphamide
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Cyclophosphamide Versus Placebo in Scleroderma Lung Study

Resource links provided by NLM:


Further study details as provided by The University of Texas Health Science Center, Houston:

Primary Outcome Measures:
  • Forced Vital Capacity [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    The primary end point was the forced vital capacity (FVC, expressed as a percentage of the predicted value) at 12 months, after adjustment for the baseline FVC.


Secondary Outcome Measures:
  • Total Lung Capacity [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    expressed as a percentage of the predicted value

  • DLCO [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    diffusing capacity of the lungs for carbon monoxide


Enrollment: 158
Study Start Date: August 1999
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cylophosphamide
Cyclophosphamide (Cytoxan, Bristol-Myers Squibb) was initiated with a dose of 1 mg per kilogram of body weight per day (to the nearest 25 mg). The doses were increased monthly by one capsule up to 2 mg per kilogram.
Drug: Cyclophosphamide
Cyclophosphamide (Cytoxan, Bristol-Myers Squibb) was initiated with a dose of 1 mg per kilogram of body weight per day (to the nearest 25 mg). The doses were increased monthly by one capsule up to 2 mg per kilogram.
Other Name: Cytoxan (Bristol Myers Squibb)
Placebo Comparator: Placebo
Matching gel caps at a dose of 25 mg
Drug: Placebo
Matching gelcaps 25 mgs
Other Name: Placebo

Detailed Description:

BACKGROUND:

Systemic sclerosis is a connective tissue disease of unknown etiology characterized by microvascular injury and excessive fibrosis of the skin and viscera. In the United States, 5,000 to 10,000 new cases are diagnosed annually. Approximately 80 percent of these persons will eventually develop some degree of lung involvement, and restrictive lung disease (interstitial fibrosis) is now the leading cause of morbidity and mortality in systemic sclerosis. An inflammatory alveolitis is thought to be the precursor of interstitial pulmonary fibrosis in systemic sclerosis. An effective treatment for SSc interstitial lung disease has yet to be identified. Cyclophosphamide (CYC) is already being widely used by rheumatologists desperate to do something to halt rapidly declining lung function in SSC patients. Thus, the time is ripe to perform a placebo-controlled trial of CYC in this disease.

Pulmonary scleroderma strikes all races and is most prevalent among women during their child-bearing, child-rearing, and working years. A positive outcome from this trial, demonstrating that oral cyclophosphamide has a beneficial effect on pulmonary fibrosis, would be of great importance by offering a scientific basis for treatment. Similarly, a negative result, demonstrating no benefit from cyclophosphamide therapy, would also be important in avoiding hazardous and expensive therapy that is now being used widely.

DESIGN NARRATIVE:

Multicenter, placebo-controlled, randomized, double-blind. Subjects are recruited at 12 clinical centers and randomized to 2 mg/kg/day of cyclophosphamide or placebo. Follow-up visits for pulmonary assessments occur every three months for two years after treatment. If patients fail the cyclophosphamide treatment, they will be offered azathioprine for the remainder of the 24 month trial. The primary endpoint of the study is change in forced vital capacity at the end of 12 months of treatment. Secondary endpoints include quality of life, activity, and dyspnea indices, and carbon monoxide diffusing capacity. Recruitment ends in December, 2003.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with limited or diffuse systemic scleroderma if they had evidence of active alveolitis on examination of bronchoalveolar-lavage (BAL) fluid (defined as neutrophilia of ≥3 percent, eosinophilia of ≥2 percent, or both)on thoracic high-resolution computed tomography (CT), any ground-glass opacity,
  2. Onset of the first symptom of scleroderma other than Raynaud's phenomenon within the previous seven years,
  3. An FVC between 45 and 85 percent of the predicted value
  4. Grade 2 exertional dyspnea according to the baseline instrument of the Mahler Dyspnea Index (as measured with the use of the magnitude-of-task component).

Exclusion Criteria:

  1. A single-breath carbon monoxide diffusing capacity (DlCO) that was less than 30 percent of the predicted value,
  2. A history of smoking within the preceding six months, other clinically significant pulmonary abnormalities,
  3. Clinically significant pulmonary hypertension requiring drug therapy.
  4. Patients taking prednisone at a dose of more than 10 mg per day, those who had previously been treated for more than four weeks with oral cyclophosphamide or had received two or more intravenous doses,
  5. Patients who recently received other potentially disease-modifying medications.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00004563

Sponsors and Collaborators
The University of Texas Health Science Center, Houston
Investigators
Principal Investigator: Maureen Mayes The University of Texas Health Science Center, Houston
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Maureen Mayes, Professor and Elizabeth Bidgood Chair in Rheumatology, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier: NCT00004563     History of Changes
Other Study ID Numbers: 220, U01HL060839
Study First Received: February 9, 2000
Results First Received: February 19, 2015
Last Updated: March 5, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by The University of Texas Health Science Center, Houston:
Lung Diseases
Pulmonary Fibrosis
Systemic Scleroderma
Scleroderma, systemic

Additional relevant MeSH terms:
Scleroderma, Diffuse
Scleroderma, Localized
Scleroderma, Systemic
Lung Diseases
Pulmonary Fibrosis
Connective Tissue Diseases
Respiratory Tract Diseases
Skin Diseases
Cyclophosphamide
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on April 23, 2015