Scleroderma Lung Disease:
Scleroderma is associated with two kinds of lung disease – interstitial lung disease (also called pulmonary fibrosis) and pulmonary hypertension. The Scleroderma Lung Study is focused on the treatment of pulmonary fibrosis. Pulmonary fibrosis occurs when scleroderma produces inflammation and scarring of the air sacs that make up lung tissue. When scar tissue forms in the lung, the tissue becomes thicker and stiffer, making it difficult for patients to take a normal breath and for the lungs to take up oxygen. Pulmonary fibrosis occurs in about 70-80% of people with both limited and diffuse scleroderma. Patients may not have symptoms with early disease but develop symptoms like increasing shortness of breath with exercise, cough, and dizziness as lung involvment progresses. Tests such as chest x-ray, CT scan the chest, and lung function studies are used to look at the degree of lung involvement. About 15% of patients with lung fibrosis progress to “severe” levels of lung disease. This decline typically happens during the first 4-6 years after onset of scleroderma.
Scleroderma Lung Study II ( “SLS II”):
SLS II is a clinical research study focused on treating scleroderma-related pulmonary fibrosis. It is funded by a grant from the National Heart, Lung and Blood Institute of the National Institutes of Health. This study compares 2 different medications—daily oral cyclophosphamide (CYC, also called CytoxanTM) with daily oral mycophenolate mofetil (MMF, also called CellceptTM). Both medications have shown promise in stabilizing lung function in patients with pulmonary fibrosis. CYC was tested in a prior research study (SLS I) for scleroderma-related lung fibrosis and was associated with significant improvements that lasted for up to one year after the drug was stopped (see: “Results from SLS I Study”). In SLS II, MMF is being examined to see if it is as effective as CYC and to determine whether its effects might last longer. However, at this time, we don’t have enough information to know whether one medication works better or is safer than the other.
If you give your consent to participate in the SLS II research study and are found to be eligible to be enrolled as a study patient, you will be randomized to receive either daily cyclophosphamide (CYC, also called CytoxanTM) or mycophenolate mofetil (MMF, also called CellceptTM) as an experimental treatment for your lung disease. You can learn more about randomization and what it means to be involved in a research study in the section on “What is a clinical trial”. Both of these study drugs are prepared as identical appearing capsules that are taken by mouth. This is a randomized double-blinded study, which means that neither the enrolled patients or their treating physicians will know which of the study drugs they are receiving. The study capsules will be taken twice daily for two years, although those patients enrolled into the group receiving CYC will only receive active drug for the first year and then an identical appearing placebo (sugar pill that contains no active medication) for the second year. Those patients that are assigned to the MMF group will receive active study drug for the entire two years.
The SLS II study is being conducted at 12 different centers throughout United States (see section on “The 12 Study Centers”) and we plan to recruit a total of 150 patients to participate. Before you can participate in the study, you will have to provide past medical records about your disease and then undergo a series of tests to find out if you are eligible to be in the study. These tests include a complete history and physical examination, blood tests, lung function tests (also called pulmonary function tests), and a CT scan of your chest.
To be eligible to participate in SLS II, patients must meet the following criteria:
- Be between 18 and 75 years old
- Have either limited or diffuse scleroderma for no more than 5 years
- Have shortness of breath
- Have decreased lung function
- Not have other serious illnesses
Meet other eligibility criteria that you study doctor will explain to you as part of the evaluation process. If you are eligible, you will be randomized to receive treatment with either CYC or MMF as described above.
The premise for this study is that 2 years of daily MMF will be more effective and safer than one year of daily CYC. However, there is currently not enough evidence to know if this premise is true, which is why it is being tested in this research study.
Study-related visits:
Once you start the study drug, you will be checked at least monthly for study medication side effects. This will be monitored using urine and blood tests. You may or may not have to come to the study site for these tests. You will see the study doctor every 3 months to check the effectiveness and safety of the study drug. During these visits, you will have a physical examination, complete several questionnaires to see how well you are doing, and have a lung function study. At the end of the study you will also have another CT scan of the chest.
What happens if I don’t do well or have side effects:
Being a voluntary study, you can drop out at anytime during the study. In addition, we have developed guidelines to ensure your safety. In case of certain types of adverse events or worsening of your scleroderma (including your lung disease), we may decide to decrease the dose of the study drug or completely take you off the study drug and work with your own doctor to start another therapy. In all cases you will be closely followed and your safety and treatment will be our first consideration.
Cost to you or your Health Insurance:
The costs of the study drugs and laboratory testing (blood and urine) for monitoring potential study drug toxicity, and the costs of attending the study center for each of the study visits, will be paid for by the study. However, the lung function tests and chest CT scans are considered standard of care for your condition and will be billed to your health insurance. If you have a co-payment, no insurance or your insurance does not cover the entire costs of these tests, then the study will cover these amounts for you. Other medical expenses that you may incur as part of the regular management of your scleroderma, which are not related to this specific study, will not be paid for by the study. You should discuss this with your study physician before you decide to participate in SLS II.