Scleroderma Lung Disease (SLS)

March 5, 2015 updated by: Maureen Mayes, The University of Texas Health Science Center, Houston

Cyclophosphamide Versus Placebo in Scleroderma Lung Study

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

158

Phase

  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • Cytoxan (Bristol Myers Squibb)
Placebo Comparator: Placebo
Matching gel caps at a dose of 25 mg
Drug: Placebo
Matching gelcaps 25 mgs

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total Lung Capacity
Time Frame: 12 months
expressed as a percentage of the predicted value
12 months
DLCO
Time Frame: 12 months
diffusing capacity of the lungs for carbon monoxide
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Texas Health Science Center, Houston

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

  • Principal Investigator: Maureen Mayes, The University of Texas Health Science Center, Houston

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 1999

Primary Completion (Actual)

May 1, 2013

Study Completion (Actual)

May 1, 2013

Study Registration Dates

First Submitted

February 9, 2000

First Submitted That Met QC Criteria

February 9, 2000

First Posted (Estimate)

February 10, 2000

Study Record Updates

Last Update Posted (Estimate)

March 27, 2015

Last Update Submitted That Met QC Criteria

March 5, 2015

Last Verified

March 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 220 (Other Identifier: Greater Manchester Mental Health NHS Foundation Trust)
  • U01HL060839 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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