Cannabinoids in Multiple Sclerosis Trial
Press release on long-term results (10/09/04)
The cannabis plant contains more than 60 different cannabinoids, the most active of which is thought to be tetrahydrocannabinol (THC). Over the last few years, discoveries have demonstrated that we all have cannabis-like chemicals, called endocannabinoids, in our nervous systems. Although we have some insight into the function of these chemicals, such as helping to control appetite and influencing communication between nerve cells in the brain, we are a long way from fully understanding their role in healthy people.
Cannabinoids have been used as medicines for many thousands of years, but until recently there has been little scientific evidence for any therapeutic benefit. This has led to many thousands of people using cannabis illegally in conditions such as multiple sclerosis (MS), to alleviate some of their symptoms. Recent experiments in the laboratory have also suggested that these compounds may help to protect the nervous system from damage, which has potential benefit to many human diseases in which nerve cells die prematurely.
In the CAMS study we set out to test whether cannabinoids have any therapeutic value in the treatment of MS. We chose to focus on muscle stiffness (technically termed spasticity) as the main symptom to be measured in the trial, but we also wanted to examine any other potential benefit by measuring disability and symptoms in a number of other ways. People with MS and significant spasticity were allocated to receive capsules containing either a whole extract of cannabis, THC or placebo (dummy capsules). The main study lasted for 15 weeks. After this time, all patients discontinued their study treatment for a few days but were then given the option of recommencing the same medication for up to one year.
The design of the CAMS study illustrates some of the major issues associated with clinical trials, namely which treatments to use, what measurements to make, and how to deal with any potential bias. In the case of the CAMS study, bias could have been introduced because the known side effects of cannabinoids could have made patients aware of whether they were taking active medication or placebo.
The results from the 15-week study were published in the Lancet late last year, and showed that from the patient perspective, these medicines were very helpful in managing the chronic symptoms of MS. However, when an independent physiotherapist estimated muscle stiffness, no objective evidence of spasticity reduction could be found. We did find some improvement in walking time in people still able to walk, but overall there was no benefit in the disability scales used. These results have to be interpreted in the knowledge that many patients receiving active medication correctly guessed that they were not taking dummy capsules, whereas those on the dummy capsules guessed correctly at no more than chance levels, maybe leading to a degree of bias. We did find a large placebo effect, which probably reflects the benefits of taking part in clinical trials for most people.
After the main study, we continued to monitor patients for up to a year to see if we could find any longer-term benefit or identify any side effects. Initial results suggest that there may be more benefit over the longer-term than we found over the first part of the study. These results must be regarded as preliminary, as the study was only designed to be a short-term study, and for various reasons, we were only able to collect long-term data on 80% of our original participants. Nonetheless, there may be longer-term benefit to people with MS, which needs further careful evaluation in more clinical trials.
This work illustrates many of the difficulties in conducting clinical trials in chronic disease, and providing scientific evidence where very little has existed before. The study has enabled us to develop better methods of evaluating symptoms, but much more work is necessary to establish whether any effect on symptoms can be differentiated from an effect on the underlying disease course.
Preparation of long-term results (26/02/04)
Analysis of the long-term data from the study (weeks 16-52) is now being undertaken. These results and details of publication will be available on this site in due course. As with the first phase, all participants will receive a results summary by post.
Results published (07/11/03)
We are pleased to announce that the results of the first fifteen weeks of the study are published in the Lancet this week (8 November 2003 edition). Click on the 'Results' button to view a summary. If you have any questions please feel free to contact us at cannabis-trial@pms.ac.uk
Most participants were on the study for one year, and our findings for the second phase of the study (weeks 16 to 52) will follow in due course.
For further information on funding research within the Peninsula Medical School, please contact Peninsula Medical Discovery Funds.
Results due (03/11/03)
The findings of the study are to be published shortly - click on the 'Results' button to go to the results page. For those who wish to access the full scientific paper, a link will be provided to the medical journal in which the results are published.
Latest update (09/10/03)
The final results paper has now been submitted for publication and is currently undergoing the review process as explained below. A summary of the results will be available on this site in due course.
Progress Report (10/09/03)
We are currently in the process of preparing the results of the study for publication.
The results will shortly be submitted to a medical journal and must undergo a process of peer-review before being accepted for publication. We may be asked to make some adjustments to the report before it is finally approved for publication but will make every effort to ensure that delays are minimised as far as possible. Hopefully the results will be made public before too long, and all participants will then receive a copy of the results, as promised.
Feedback Questionnaire (31/07/03)
Whilst we wait for the results of the study to be announced, we are taking the opportunity to reflect on how the study was conducted. We are keen to find out which aspects participants felt went well, and in which areas improvements could have been made. To help with this, we have sent all participants a short questionniare, asking for their feedback about various aspects of the study. So far, we have had a marvellous response, with over 400 questionnaires being returned during the past fortnight. If you have not yet completed and returned your questionnaire, there is still plenty of time to do so.
Update on study results (19/06/03)
Although data analysis is still progressing well, producing the results of the study will take slightly longer than anticipated. We estimate that the results will now be made public in early September 2003, at which time all participants will be individually informed. As indicated previously, a summary of the study results will subsequently be available on this website.
Study results due in July (06/06/03)
Data analysis is progressing well and the results of the first phase of the study are due to be made public in mid-July. All trial participants will be individually notified of the results at this time and a summary of the study results will subsequently be available on this website.
Analysis is due to start (04/04/03)
All the data from the first phase of the study has now been collected, checked and entered into the study database. Analysis of the data is due to begin imminently, so that results can be published as planned in July 2003. It has been decided that the trial will officially end on 30 June 2003 but until then patients may continue to participate in the second phase of the study as usual.
First Phase Complete (04/03/03)
All trial participants have now completed the first 15 weeks of the study, which constitutes the main part of the CAMS trial. During the next few weeks the trials team in Plymouth will be busy checking that all the first phase data is complete and that any outstanding queries are resolved. Once this important process is finished, statistical analysis can begin. We envisage that results will be available, as planned, by summer 2003.
Meanwhile, although the majority of participants have completed their year of study follow-up, approximately 200 patients are still taking part in the second phase of the study. This part of the study will also give us important information, and analysis of our long-term data will follow later in the year.
Recruitment Complete (11/10/02)
Recruitment to the trial was completed yesterday, when the last patient attended for their screening visit. In total 667 patients have entered the trial, slightly more than the target number of 660. This provides a large, statistically meaningful, number of patients which will help us to provide a clear answer to the question of whether or not cannabis can help the symptoms of MS. We will need to wait until the patients just recruited have reached the end of the initial 15 week phase of their treatment before we can begin analysing the results in February 2003. We hope to announce the results of the trial in summer 2003. A big thank you is due to all the centres and patients who have helped us to reach this stage.
Recruitment expected to finish by end of September (3/9/02)
With only 17 patients to go before reaching our target of 660, we currently hope to have finished recruitment to the study by the end of September. Check the very latest recruitment figures here. Once recruitment is complete, it will be 4 months before the massive task of analysing all the data can begin.
CAMS Follow Up Study (2/8/02)
As you may know the trial team have been looking at ways of enabling patients on the present CAMS study to continue on their allocated trial medication beyond the study phase of the MRC funded clinical trial.
One of the options we were investigating was the possibility of a follow up study of participants. We discussed funding with the MS society, including ways of amending a research proposal submitted to them a few months ago.
However, after discussing the possibilities, the trial team and the MS Society have agreed that at this late stage in the CAMS trial there would not be time to design and undertake such a study before the MRC funded trial ended. Therefore, it now appears that there is no possibility of enabling the present cohort of patients in the CAMS study to continue on their allocated trial medication as part of a follow up study attached to the trial.
The MS Society has invited the trial team, to submit a new application for funding a study to address long-term issues in the use of cannabinoids in the treatment of MS, which would extend the information obtained from the present study.
Dr Zajicek, one of the principal investigators, is exploring other means of enabling CAMS patients to receive medication outside of the clinical trial, but within existing medicines licensing rules.
The main CAMS study is continuing well, and is expected to complete recruitment by the autumn, with results becoming available in spring/summer 2003.
Long term follow up application will be resubmitted (26/6/02)
The research team and the MS Society have been discussing the application submitted to them for long term follow up of participants on the CAMS study. The discussions and clarifications have been useful and we are now making amendments to the application to address some points raised by the MS Society research panel. The Society is helpfully making arrangements to review the request for funding again as quickly as possible after receipt. We are currently preparing the application for resubmission to the Society. We would reiterate that this application is purely for a long term follow-up study - the main CAMS trial is fully funded by the MRC and is continuing to recruit patients from around the country.
Long term follow-up phase turned down (29/5/02)
We have heard today that our application for funding of an extension to the study has been turned down by the MS Society. This would have allowed patients who had perceived benefit from their medication to remain on treatment beyond the one year of the main trial (see below). The main trial will continue as planned but, unless we can make alternative arrangements for funding, all patients will have to stop their medication after one year's treatment.
"Your Trial Needs You"! (28/03/02)
Recruitment has been going well over the first part of the year, and as we pass the two-thirds mark its tempting to relax and think that we're nearly there. But we still need nearly another 200 patients to reach our target. If recruitment continues at the current rate its realistic to hope to be there by the summer, but that relies on everybody who's promised to recruit more patients doing so. We're very grateful for everybody's help so far, and look forward to the stream of randomisations continuing to take us through to the summer.
Extension to the study (28/03/02)
Many patients who have perceived some benefit from the trial treament have been asking what will happen at the end of their year of treatment. We are pleased to be able to say that we are in the process of applying for funding from the MS society for an extension to the study. This would allow patients who wish to continue on medication to do so until the results of the main study are made public, hopefully in spring 2003. All principal investigators have been sent details of the extension and most have indicated their willingness to take part. Further details will be made available once funding is secured.
Over Halfway (03/01/02)
The halfway point was passed on the second of January, when Ipswich randomised the 330th patient. Many centres are starting second or third cohorts of patients and there continues to be considerable enthusiasm for the trial. We thank everyone involved for keeping us on target, and look forward to a continuing climb in numbers in the New Year.
Halfway by Christmas? (14/12/01)
The trial continues to progress well, with steady recruitment around the country. At the present time, 319 patients have been randomised. We know of a few centres who are planning further randomisations between now and Christmas and so hope to reach the halfway mark (330) very soon... Check for the very latest patient numbers here.
20% of Target Achieved (07/08/01)
Twenty percent (132 patients) of the target of 660 patients have been recruited around the country. Fifteen of an anticipated thirty-eight centres are seeing patients with several more expecting to start after the summer break later in August or September. As national recruitment has only been ongoing for two months, this means we are on schedule to reach full recruitment after a total of one year. Check for the very latest patient numbers here.
Recruitment Starts Around the Country (01/06/01)
The first centres outside Plymouth have begun recruiting patients to the trial. Check the "Active Centres" page to follow the progress of the trial around the country.
Training Days Successfully Completed (01/06/01)
The five training days have now finished. Thanks to everyonewho attended, and who provided some very positive feedback as to their usefulness. We are aware that some centres have yet to find a suitable back-up assessor, and that a few centres have still not identified their main assessor. We plan to address this with a further training day in the late summer for these personnel. In the meantime, Steve will be visiting many centres over the next couple of months to see how well the lessons of the training days have been learnt.
Study Moving Nationwide (11/5/01)
The first cohort of 20 patients have finished the first 15 week phase of the study in Plymouth. This has allowed us to ensure that there are no problems with the practicalities of the study. We are now ready to expand the study around the country. Once the training days are over at the end of May other hospitals will begin recruiting patients.
Training Days (28/3/01)
The first of 6 training sessions is being held today in Plymouth for staff at hospitals in the southwest. The aim of these half-day meetings is to introduce the trial to doctors who will be taking part, go over the case record forms that will need to be filled in and to train assessors (doctors or physiotherapists) in the use of the Ashworth scale. Todays's session is in Plymouth, but future ones will be in Bristol, Leeds, Birmingham and London to accommodate the many sites around the country which are interested in taking part. See further details here.
Long Term Phase Approved (28/3/01)
The Medicines Control Agency has provided approval for the long term (15-52 weeks) phase of the study to go ahead.
TV Documentary (18/01/01)
The BBC filmed patients in Plymouth being recruited for the trial before Christmas. Viewers in the southwest region saw the half-hour BBC2 program - "Close-Up: Stiff Joints" on Thursday 18th January 2001 at 7:30pm - "Report on the cannabis trials taking place in the South West, which researchers hope will prove whether the plant can alleviate the pain of diseases including multiple sclerosis. Sufferers of the illness speak out about the effect the drug has had on their lives."
Plymouth Patients Recruited (09/01/01)
The first group of 21 patients has now been recruited in Plymouth. They have all attended their screening visit and will start on medication later in January. We know that patients in the rest of the country are impatient to get started, but to ensure everything runs smoothly we plan to follow this first group of patients through their first 16 weeks before rolling the trial out nationally. This will take us to the beginning of May. Allowing time to make any alterations needed in view of our experiences with these first patients, we now expect recruitment to be taking place in the rest of the country in June.
The First Clinics (12/12/00)
The first clinics will be starting in Plymouth to screen patients in the week before Christmas. Patients will start taking the drugs a month after that, in mid January. We are on schedule to expand the trial to the rest of the SouthWest region in March, and the rest of the country over the following 6 months.
Bottling the Drugs (29/11/00)
The drug is now in the country and is currently being bottled. This process takes some weeks, but we are still on schedule for the first patients in Plymouth to be recruited in early 2001.
Importing the Drugs (1/11/00)
The cannabis plants for the trial have been grown in Switzerland. The active constituents of the plants have been extracted and imported into Germany for encapsulation. This process is now finished and the drug awaits importing into Britain and bottling before the trial is ready to start - this will take about a futher six weeks.
LUTS study funded (4/9/00)
The "Lower Urinary Tract Symptoms" study has received funding from the MS Society to run alongside the CAMS study in the southwest, looking specifically at the effect of cannabis on the bladder symptoms that some multiple sclerosis sufferers experience.