Cannabinoids in Multiple Sclerosis Trial
Patient Information Sheet
Voluntary Participation in CAMS Study
You are being invited to take part in a research study. Before you decide 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. Take time to decide whether or not you wish to take part. You are welcome to discuss your possible participation in the study and alternative treatments with your family and your own doctor and other sources of advice such as the Multiple Sclerosis Society, whose Helpline can be contacted on 0808-800-8000.
Consumers for Ethics in Research (CERES) publish a leaflet entitled "Medical Research and You". This leaflet gives more information about medical research and looks at some questions you may want to ask. A copy may be obtained from CERES, PO Box 1365, London N16 0BW.
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Introduction
Multiple Sclerosis (MS) is the commonest cause of neurological disability in young adults. Of the many symptoms frequently encountered in MS, muscle spasticity (stiffness) and spasms occur in up to 90% of patients at some point in their illness. Unfortunately, current therapies for spasticity often provide inadequate relief and are limited by side effects. There are many anecdotal reports that the drug cannabis (the use of which is currently illegal) is a useful alternative treatment for muscle spasticity. However, there is only limited scientific evidence to support this fact. In order to find out if cannabis really does relieve muscle spasticity, a study such as this one is needed.
What sort of study is this?
This is a research study where we are trying to compare the effect of three different treatments on muscle spasticity (stiffness) in patients with MS. The treatments are in capsules, which are swallowed. Two of the treatments contain active drugs. One is prepared from the cannabis plant and contains a balance of all the chemicals present in the plant. It is called cannabis oil. The second treatment contains a single chemical compound which is found in the cannabis plant, called tetrahydrocannabinol (THC). Each of these will be compared with a treatment which looks the same as one of the active drugs but contains no active drug and is called a placebo. This means that neither you nor your doctor will be able to tell if you are taking one of the active treatments or one of the placebos.
Each participant in the study will be allocated to receive just one of the possible treatments. Because it is not known which of the treatments will be most useful in helping spasticity, a comparison will be made. Your treatment will be determined when you start the trial and will be chosen randomly by a computer so that one third of patients are allocated to each type of treatment. In order that unbiased assessments can be made, neither you nor your doctors will know which treatment you are receiving.
Am I suitable for the study?
We are looking for volunteers who have MS and are aged between 18 and 65 years. In order to be included in the study:
- You must have some muscle stiffness in the legs.
- You should also have not suffered any relapses in the last 6 months.
- You must not have taken any cannabis in the last month.
- If there is a possibility that you may be pregnant you may not participate in this study.
Because cannabis may interfere with your ability to concentrate, you may only take part in the study if you are able to stop driving for the study period (15 weeks) and a week after that (total 16 weeks). This also applies to operating dangerous machinery. You must therefore not drive or operate dangerous machinery for a total of 16 weeks over the trial period. If you and your doctor feel that the medicine which you were taking over the 15 weeks study period was effective in controlling your symptoms, then you could continue to take the medicine for the remainder of the year. Because, outside the setting of the trial, cannabis is an illegal drug it is especially important you do not under any circumstances pass on your medication to anyone else, nor should you take the drugs out of the country. Therefore any holiday plans which take you abroad must be before or after the first 16 week period of the trial.
What drugs will I be given?
You will be given only one of three possible treatments, which are;
- Capsules containing no active drug (called a placebo) which look identical to one or other of the active treatments.
- Capsules containing natural cannabis oil (containing many natural plant substances).
- Capsules containing tetrahydrocannabinol (THC), this is one of the active chemicals in cannabis plants.
These capsules are taken by mouth. You will not be given anything to smoke. There will be an equal chance of being allocated any one of these treatments. Neither you nor your doctor will be informed which one you have been given. . Both green and white capsules of different shapes are being used in the trial, but neither the colour nor the shape indicates whether the capsule contains active drug or placebo.
What if I am already taking medication for spasticity?
You should continue with your current medication. Your doctor will make sure that you are on the optimal dose before you start the study.
How long will I have to take the treatment for?
You will be asked to take the capsules for at least 14 weeks. Your doctor will adjust the number of capsules you need to take each day during the first two to five weeks. When the correct dosage has been found you will continue taking the same amount each day for the next eight weeks. At the end of this period the dose will be reduced over a week and then there is a further week off treatment before the end of this phase of the study. If you find that the treatment has been effective for you, then there will be the opportunity to continue taking the capsules for a period of up to nine months after the end of the initial 15 week study period. You will again be advised not to drive or operate dangerous machinery over this period, which may affect your decision to take part in this phase of the study. You will in any case need to attend the clinic every 3 months for the remainder of the year. We will not know what treatment you were taking until the end of the whole trial, but if you wish to know at that stage it will be possible for you to find out.
What risks are there to my health?
Cannabis can cause an increase in heart rate and a reduction in blood pressure. For this reason, patients with a history of heart disease will not be permitted to take part in the study. There may be other illnesses which might exclude you from participation in the study. This will be assessed by your local neurologist. In assessing the safety of cannabis the House of Lords Select Committee found that no-one has ever died as a direct result of recreational or medicinal use of cannabis. There is no convincing evidence for any long term toxic effects of cannabis.
What side effects may I experience?
You may not notice any adverse effects from whichever drug you are given. Possible side effects can include a state of euphoria (also called a "high") although it should be noted that in previous studies some patients taking the placebo drug have also experienced this. Other possible symptoms include increased appetite, weakness, dry mouth, dizziness and poor concentration. Any new symptoms must be recorded in your patient diary and discussed with the study doctor at your next clinic visit. It may be necessary to adjust the dose of your treatment in the light of any side effects.
Because these medicines may affect your alertness, you are advised not to drive or operate dangerous machinery whilst taking part in the study.
What are the advantages of taking part?
You have a 2 in 3 chance of receiving an active treatment which may help your muscle stiffness. You will also be helping in an important trial to decide the usefulness of cannabis and THC as a treatment for multiple sclerosis.
How often will I have to see the doctor?
You will need to come to the clinic for a preliminary visit, then on 7 occasions over the main trial period of 15 weeks, then a further three visits over the remainder of the year. On each of these visits your doctor will ask about side effects of your medication. On 5 of the visits you will also be examined by someone who has no knowledge of any side-effects you may be experiencing, and this may either be a physiotherapist or a doctor.
If you are already taking medication for muscle spasticity your study doctor will need to ensure you are taking the best dosage before you are formally entered into the trial. There is then a 5 week period during which your doctor will give advice about increasing the number of daily capsules, so that in the first week you will be taking one capsule twice a day, after breakfast and after your evening meal. You will be asked to increase the number of capsules to two capsules twice a day after the first week, and to return to the clinic at the end of the second week. If you experience side effects which you find totally unacceptable, then you will be asked to reduce the dose to the previous week's level. Your study doctor will record any side effects you experience when you see him or her after 2 weeks. They will then explain how to increase the capsules further over the following 2-3 weeks, again depending on whether you experience any side effects which you find unacceptable. Once you are at your target dose (which for most people will be between 2 and 4 capsules twice a day), your doctor will ask you to keep taking the medication for a further 8 weeks, before telling you how to reduce the tablets over one week. If you feel your treatment has helped you will then have the option of continuing with it for the remainder of the year. In any case, you will need to return for three further assessments.
What tests will be performed on me?
A doctor or physiotherapist will need to test the stiffness in your muscles on eight separate occasions. If you are able to walk, then the same person will time how long it takes you to walk 10 meters, using whatever aids you usually require. You will be asked to complete questionnaires when you enter the study and on 3 other occasions. Please complete these questionnaires on the day requested, and post them back to Plymouth in the self-addressed envelope provided. If you have any problems filling in the questionnaires, please ring the office in Plymouth where there should always be someone to help during normal office hours. If the research nurses at the Plymouth office have not received your questionnaires within a few days of the expected date, they may ring you at home to check everything is alright and to offer any help you may require. The questionnaires will ask you about your quality of life and how MS affects day to day life. You will also be required to indicate how you think the treatment is affecting you.
Each time you come to the clinic you will have a urine test to check for the presence of cannabis. IT IS MOST IMPORTANT THAT YOU DO NOT TAKE ANY EXTRA CANNABIS PREPARATIONS OVER THE STUDY PERIOD, as this will make it very difficult for the investigators to interpret the results. Such preparations include Nabilone and smoked cannabis.
If you are attending the Plymouth or London Queen Square centres you will also be asked for blood samples. These will be used to measure the amount of the drug in your bloodstream to provide information about how well cannabis is absorbed when taken orally and its effect on your body. It will not be used for purposes unrelated to the study of cannabinoids.
Will I have to pay for travel?
No, any specific travel costs to do with the study will be provided.
Will my medical records be confidential?
All health information will be kept strictly confidential. Your medical records may only be studied by the doctors looking after you, the organisers of the trial and those people who are being asked to monitor and oversee the safe running of the trial.
Your rights
Your participation in the study is entirely voluntary. You may withdraw at any time. This will not affect your current or future treatment in any way.
If you agree to take part your general practitioner will be informed.
You will be told of any new findings from other studies that might affect your decision to stay in the study.
The organisers of the study do not believe you will suffer any injury by participating in this study. The MRC as funder of a trial accepts responsibility for its sponsorship of the trial, and as such would give sympathetic consideration to claims for any non-negligent harm suffered by individuals as a result of participating in the trial. (This would not extend to non-negligent harm arising from conventional treatment where this is one arm of a trial.) Like other publicly funded bodies, the Council is unable to insure and thus cannot offer advance indemnity cover for participants in MRC-funded studies. Your right at law to claim for compensation for injury where you can prove negligence is not affected.
After you have agreed to take part in the study, you will be asked to sign a consent form.