Trial Co-ordinating Centre
Department of Rheumatology
Room 3.55 Weston Education Centre
King's College Hospital
Denmark Hill
London SE5 9PJ
Telephone: 020 7848 5791
Fax: 020 7848 5754
PATIENT INFORMATION SHEET
The SELAM Study
Full Title of the Study: Second Line Agents in Myositis
Study Sponsor: Arthritis Research Campaign
We would like to invite you to take part in a research study because you have an inflammatory myositis. Before you decide whether to take part, it is important for you to understand why the research is being done and what it will involve. Please take time to read the following information carefully. Feel free to discuss it with friends, relatives and your GP if you wish. Ask us if there is anything that is not clear or if you would like more information. In addition Consumers for Ethics in Research (CERES) publish a leaflet entitled ‘Medical Research and You’. This gives information about medical research and deals with some questions you may want to ask. Copies of this leaflet are available from CERES, PO Box 1365, London N16 0BW.
Background and purpose of the study
Inflammatory myositis is the name given to a group of diseases that cause inflammation in the muscles of the body. Dermatomyositis and polymyositis are the main types of inflammatory myositis. Muscle inflammation causes pain and weakness. Many patients become disabled because of damage to the muscles. In severe cases, especially when muscles of the lung and heart are affected, the disease may have very serious consequences.
Steroids have been used as the main treatment for inflammatory myositis for a long time. But in many patients they do not suppress inflammation completely. Long term treatment with steroids also often leads to side effects such as high blood pressure, diabetes and thinning of the bones.
The inflammation in myositis is mediated by the immune system of the body. Suppressing the immune system with drugs such as methotrexate and ciclosporin is often used to treat chronic inflammatory diseases. Preliminary studies suggest these drugs may be effective in inflammatory myositis. This includes reducing pain, improving function and allowing reductions in the doses of steroids.
What is the purpose of the study?
This study will determine whether methotrexate, ciclosporin or both together are effective treatments for inflammatory myositis.
Why have I been chosen?
You have been asked to take part because you suffer from myositis and are taking steroids as treatment. In this study we plan to look at the effect of methotrexate and ciclosporin in 92 patients with myositis.
Do I have to take part?
It is up to you to decide whether to take part. If you do decide to take part, you will be given this information sheet to keep and asked to sign a consent form. You will always be free to withdraw at any time without giving a reason. This will not affect the standard of medical care you receive.
What will happen to me if I take part?
If you agree to take part in this study, a research nurse or physiotherapist will contact you arrange a meeting with you at the local trial hospital. At this screening visit, he/she will make sure that all your questions are answered and will assess your myositis to ensure your disease meets the various entry criteria for the study. If so, you will be asked to sign a consent form. He/she may then arrange for you to have a muscle biopsy. This is important because we want to accurately assess your myositis. We will carry out some newer tests on these samples to make sure you do not have other muscle diseases that can cause the same symptoms and signs as inflammatory myositis. These new tests only became available recently. Unfortunately, these tests may not be able to be carried out in the old muscle biopsy samples you may have had done previously when your disease was diagnosed.
If a muscle biopsy is required, you will be given a local anaesthetic and a small cut will be made over the weak muscles. A small piece of the muscle will be cut away for the test. The wound will be stitched up with a few stitches. The biopsy area may be bruised and sore for 1 week. Very rarely, infection can occur where the muscle biopsy was done. If the site becomes very sore, red and painful, please contact your general practitioner or hospital consultant. This can be treated simply by a course of antibiotics.
If the muscle biopsy confirms that you have inflammatory myositis, you will be randomly allocated to one of the four following treatment groups. This is similar to tossing a coin. This is essential since only this type of study can tell us whether methotrexate, ciclosporin or both together are effective in inflammatory myositis.
Group 1: steroids alone.
Group 2: steroids plus methotrexate.
Group 3: steroids plus ciclosporin.
Group 4: steroids plus methotrexate plus ciclosporin.
The treatment will be continued for up to 1 year. To make it a fair comparison neither you nor your doctors (general practitioner and consultant) will know what trial medicine you are getting. To ensure this we will use inactive tablets called "placebos" in some cases instead of methotrexate or ciclosporin. If your consultant needs to find out the drug you are taking it is possible for him/her to do so.
Regularly blood test monitoring is standard clinical practice for all patients receiving methotrexate and ciclosporin. Therefore, you will have blood tests (approximately 3 teaspoons/15ml) each month. In addition to these blood tests, we would like to take a further 2 teaspoons of blood (ie 10ml) at subsequent 6 monthly visits. We will measure erythrocyte sedimentation rate and creatine phosphokinase from these samples. They measure the degree of inflammation and damage in your muscles.
Every 6 months a research nurse or physiotherapist will examine your muscles. At each visit, you will be asked to fill in questionnaires so that we can assess the effect of these treatments.
During this study you will need to make approximately 19 visits to the hospital.
What do I have to do?
Alcohol and diet
You should stop drinking alcohol while you are taking part in the study, i.e. for one year, because methotrexate and alcohol together can cause inflammation of the liver leading to cirrhosis. Grapefruit juice can affect ciclosporin so you should also avoid it during this trial.
What medicine will I be taking?
Throughout the study, you can take non-steroidal anti-inflammatory aspirin-like drugs and painkillers such as paracetamol. If you were prescribed other medicines, please remind the prescribing doctor or pharmacist that you are taking part in this trial so that he/she can make sure they can be taken with the trial medicines. Similarly, if you want to take any over the counter medicines, please discuss it with your general practitioner, hospital consultant or contact us.
Steroids
At the moment you are taking steroids for your disease. Your supervising consultant may change the dose of steroids during the study depending on the degree of inflammation in your muscles. You need to keep a diary card in your wallet/purse all the time and use it to record the dose of steroid that you are taking. This will also let other doctors know that you are taking steroids in case of emergency. It is important that you do not stop steroid treatment abruptly, this can be very dangerous. If you would like to stop or change the dose of steroid, please discuss it with your hospital consultant.
Methotrexate and Ciclosporin
Methotrexate and ciclosporin are licensed treatments for many inflammatory diseases. Their side effects are well known. They have been used safely for other diseases such as rheumatoid arthritis although regular blood tests are required. Both methotrexate and ciclosporin have been tried in a small number of patients with inflammatory myositis in preliminary studies. They have reported promising results. This study aims to test the effect of methotrexate and ciclosporin more definitively.
Methotrexate
Low dose methotrexate has been used for the treatment of chronic inflammatory diseases such as rheumatoid arthritis for many years. Low dose methotrexate reduces inflammation in rheumatoid arthritis and it is currently one of the most common anti-rheumatic drugs worldwide. Methotrexate is taken by mouth once every week. You will be starting on a low dose initially (3 tablets per week) and the dose is increased gradually. Your consultant will adjust the dose to control the myositis. The maximum dose of methotrexate will be 10 tablets per week.
Ciclosporin
Ciclosporin is another drug that is used for the treatment of rheumatoid arthritis. It is taken twice a day by mouth. Similar to methotrexate, you will be started on a low dose and if you do not have any side effects, the dose will be increased gradually. The final dose of ciclosporin will depend on your weight. Your hospital consultant will adjust the dose of the ciclosporin.
If you take part in this study, you will be given a card (similar to a credit card) to carry with you at all times. It gives information about the trial and emergency contact numbers.
What alternative treatments might I be given?
Because inflammatory myositis is an uncommon disease, the ideal treatment regimen is unknown. Steroids are the main treatment. If you decide not to take part in this study, your consultant may decide to increase the dose of steroids to reduce the inflammation in your muscles. Alternatively, he/she may add treatments similar to methotrexate and ciclosporin that suppress the body's immune system although there is no definitive evidence on how effective or toxic these treatments are in inflammatory myositis. If you have severe dermatomyositis, your consultant may also consider giving you other treatments that suppress the immune system.
What are the risks involved in the study?
Methotrexate
In some patients, methotrexate can cause sickness (nausea), diarrhoea, mouth ulcers and skin rashes. In rare cases, it can depress the blood count and makes you more prone to infection. Low blood count occurs in 1 in 70 patients started on methotrexate. If you develop a sore throat or other infection, or if you have a fever, or if you develop unexplained bruising or bleeding, or become breathless, or if you develop any new symptoms at any time after starting methotrexate, you should tell your research nurse and your consultant if it does not resolve after 1 week. However, if these symptoms are severe or you are concerned, please contact your research nurse and your consultant immediately.
Ciclosporin
In some patients, ciclosporin can cause sickness (nausea), headache, diarrhoea, gum overgrowth, mild tremor and excess hair growth. It can also cause a rise in blood pressure and damage the kidneys. We will be monitoring your blood pressure and kidney function by blood tests each month. In some cases, we may need to adjust the dose of ciclosporin.
Monitoring of treatments
As you are taking an anti-rheumatic drug, you will be seen monthly by a nurse or a hospital doctor who will measure your blood pressure and take blood tests to make sure you have not developed any side effects from the treatments. This is routine practice and will not be different in the study. There is a theoretical risk that combining the drugs may increase the chance of a side effect, especially infection, although previous studies did not find any increase risk of infection but we will check carefully for this.
Pregnancy
We do not want you to take these drugs if there is any chance of you being or becoming pregnant because they can damage any developing baby in the womb. Therefore, it is essential that you use effective contraception such as oral contraceptive pill, intrauterine devices, sterilisation, diaphragm or condom. Alternatively, you may choose, with the agreement of your partner, to abstain from sex. Women who might be pregnant may be asked to have a pregnancy test before taking part to exclude the possibility of pregnancy. If you want to become pregnant, please inform us and your consultant. We will withdraw you from the study and your consultant will discuss with you how your disease can be controlled during pregnancy. Methotrexate can affect fertility. You should not start a pregnancy until 6 months after stopping treatment with either methotrexate or ciclosporin.
For men, methotrexate can cause damage to sperm. These damaged sperm may form an abnormal baby. Therefore, you should not father a child until 6 months after stopping methotrexate treatment.
Private medical insurance
If you have private medical insurance, you should check with the company to make sure taking part in the trial will not affect your medical insurance.
What are the possible benefits of taking part?
We hope that both methotrexate and ciclosporin will help you and improve your myositis. However, this cannot be guaranteed. The information we get from this study may help us to treat future patients with inflammatory myositis better.
What if new information becomes available?
Sometimes during the course of a research project, new information becomes available about the treatment/drug that is being studied. If this happens, your consultant will tell you about it and discuss with you whether you want to continue in the study. If you decide to withdraw, your consultant will make arrangements for your care to continue. If you decide to continue in the study you will be asked to sign an updated consent form. Also, on receiving new information your consultant might consider it to be in your best interests to withdraw you from the study. He/she will explain the reasons and arrange for your care to continue.
What happens when the research study stops?
The results of the study will not be available immediately when you have completed the study. However, if you are interested in the results of the study, we can send them to you when the whole study has been completed. At the end of the trial, you will continue treatment with steroids only. If your disease worsens, either methotrexate or ciclosporin can be added if you and your consultant agree that it is appropriate.
What if something goes wrong?
If your health is adversely affected as a result of your involvement in the study, indemnity will be provided by the sponsor of the study, Arthritis Research Campaign and Guy’s, King’s College and St Thomas Hospitals School of Medicine and Dentistry, King's College London. Broadly speaking both these bodies without legal commitment should compensate you without you having to prove that they are at fault. This applies in cases where it is likely that such injury results from giving any new drug or any other procedure carried out in accordance with the protocol for the study. 'The sponsor' will not compensate you where such injury results from any procedure carried out which is not in accordance with the protocol for the study. Your right at law to claim compensation for injury where you can prove negligence is not affected. Copies of these guidelines are available on request.
Will my taking part in this study be kept confidential?
If you consent to take part in the research, any of your medical records may be inspected by the researcher for purposes of analysing the results. They may also be looked at by people from regulatory authorities to check that the study is being carried out correctly. Your name, however, will not be disclosed outside the hospital. All information that is collected about you during the course of the research will be kept strictly confidential. Any information about you which leaves the hospital will have your name and address removed so that you cannot be recognised from it. Your regular doctor (general practitioner) and other doctors who are treating you will be notified of your participation in the trial.
What will happen to the results of the research study?
The study will take at least 3 years to complete. The results of the study will be published in a medical journal. Annual reports on the progress of the study and the final results will be available through press releases and newsletters from the Arthritis Research Campaign. However, your name will not appear in any report or publication.
Expenses
This study is sponsored by the charity Arthritis Research Campaign. No payment will be made for participating in the study but reasonable travel expenses will be reimbursed.
Who has reviewed the study?
This study has been reviewed by the South Thames Multi-centre Research Ethics Committee.
What if you choose not to take part or want to stop treatment during the study?
Participation in the study is completely voluntary and a decision not to participate will in no way influence your future treatment. You may withdraw from the study at any time without necessarily giving a reason.
Thank you for taking part in this study. You should keep this Patient Information Sheet and a copy of the signed consent form.
FURTHER INFORMATION PLEASE CONTACT:
Barbara Mason (Principal Trial Co-ordinator) on 0207 848 5791
or
Dr Ernest Choy (Principal Investigator) on 0207 848 5201
For a list of participating hospitals, please click here.