Scleroderma Lung Disease (SLS)
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| ClinicalTrials.gov Identifier: NCT00004563 |
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Recruitment Status :
Completed
First Posted : February 10, 2000
Results First Posted : March 6, 2015
Last Update Posted : March 27, 2015
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Lung Diseases Pulmonary Fibrosis Systemic Scleroderma Scleroderma, Systemic | Drug: Cyclophosphamide Drug: Placebo | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 158 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Prevention |
| Official Title: | Cyclophosphamide Versus Placebo in Scleroderma Lung Study |
| Study Start Date : | August 1999 |
| Actual Primary Completion Date : | May 2013 |
| Actual Study Completion Date : | May 2013 |
| Arm | Intervention/treatment |
|---|---|
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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.
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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) |
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Placebo Comparator: Placebo
Matching gel caps at a dose of 25 mg
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Drug: Placebo
Matching gelcaps 25 mgs |
- Forced Vital Capacity [ Time Frame: 12 months ]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.
- Total Lung Capacity [ Time Frame: 12 months ]expressed as a percentage of the predicted value
- DLCO [ Time Frame: 12 months ]diffusing capacity of the lungs for carbon monoxide
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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,
- Onset of the first symptom of scleroderma other than Raynaud's phenomenon within the previous seven years,
- An FVC between 45 and 85 percent of the predicted value
- 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:
- A single-breath carbon monoxide diffusing capacity (DlCO) that was less than 30 percent of the predicted value,
- A history of smoking within the preceding six months, other clinically significant pulmonary abnormalities,
- Clinically significant pulmonary hypertension requiring drug therapy.
- 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,
- Patients who recently received other potentially disease-modifying medications.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00004563
| Principal Investigator: | Maureen Mayes | The University of Texas Health Science Center, Houston |
Additional Information:
Publications of Results:
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 ( U.S. NIH Grant/Contract ) |
| First Posted: | February 10, 2000 Key Record Dates |
| Results First Posted: | March 6, 2015 |
| Last Update Posted: | March 27, 2015 |
| Last Verified: | March 2015 |
Keywords provided by Maureen Mayes, The University of Texas Health Science Center, Houston:
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Lung Diseases Pulmonary Fibrosis Systemic Scleroderma Scleroderma, systemic |
Additional relevant MeSH terms:
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Fibrosis Lung Diseases Pulmonary Fibrosis Scleroderma, Systemic Scleroderma, Diffuse Scleroderma, Localized Pathologic Processes Respiratory Tract Diseases Connective Tissue Diseases Skin Diseases |
Cyclophosphamide Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists |