Cannabinoids in Multiple Sclerosis Trial
GP Information Sheet
Multiple Sclerosis (MS) is the commonest cause of neurological disability in young adults, with a prevalence of 1 in 800. Of the multitude of symptoms commonly encountered in MS, muscle spasticity and spasms occur in up to 90% of patients at some point in their illness, often leading to considerable distress by contributing to reduced mobility and pain, as well as interfering with day to day hygiene and ability to transfer, particularly when patients are wheelchair bound. Other disabling features reported in chronic MS include ataxia and tremor in up to 80%, disturbance of micturition in up to 80% of cases and sensory symptoms including pain in up to 40%. Although some of these symptoms may resolve during the recovery phase of early MS, spasticity, weakness and ataxia are often hallmarks of chronic progressive MS, and tend not to resolve spontaneously. Unfortunately, current therapies for spasticity often provide inadequate relief and are limited by toxicity. As a result, patients have experimented with alternative treatments including cannabis, and a considerable weight of anecdotal evidence has built up, suggesting that cannabis has therapeutic benefit to symptoms of spasticity, bladder disturbance, pain and tremor.
The study is a large (660 patient) multicentre, randomised, double-blind, controlled trial of one year's duration comparing placebo capsules with cannabis oil and tetrahydrocannabinol (believed to be the major active ingredient of cannabis). There are two placebo arms, one to match each active treatment. Patients will have relatively stable MS and significant spasticity in at least two leg muscle groups, as judged by clinicians using the Ashworth scale of spasticity. The primary outcome measure will be a reduction in spasticity using this measure, whilst secondary outcome scores will assess mobility, quality of life and disability. Most of the secondary outcome measures will be administered using a postal questionnaire, supervised by research nurses from the trial centre. Particular attention will be paid to side effects and two individuals will be used in each centre (a monitoring physician to record side effects and adjust dosage, and an assessing individual to perform blinded outcome measures) in order to maximise blinding. Patients will be adjusted on their optimal current therapy before trial entry, after which they will undergo a titration phase (5 weeks) and maintenance phase (8 weeks) before drug withdrawal (2 weeks). At the end of this 15 week period patients will have the option of continuing on treatment for the remainder of the year if they feel it has been beneficial. Patients will need to attend for a total of 7 visits within the main 15 week trial period, then a further three visits over the remainder of the year.
Patients will then be offered the opportunity to continue taking their medication for a further year if both assessor and patient have found the medication beneficial. This phase of the study will also be carried out in a double blind fashion, with 3-monthly visits to the clinic.
Particular points worthy of note are as follows:
- Patients will be advised that they should not drive or operate dangerous machinery for the duration of the study.
- Patients will be optimised on current anti-spastic therapy for at least 4 weeks prior to study entry.
- The titration phase of the study will last 5 weeks and doses will be adjusted according to side effects, aiming for a target dose according to body weight.
- Patients will be advised to contact the co-ordinating office in Plymouth if they have any concerns. A research registrar or nurse will be available for advice during working hours throughout the study.
- If you have any concerns at any stage, please feel free to contact either the investigating clinician looking after your patient in the study, or the co-ordinating centre in Plymouth.