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© CAMS Trial 2001
CAMS Study
A Multicentre Randomised Controlled Trial of Cannabinoids in
Multiple Sclerosis
Principle InvestigatorsDr John Zajicek
Dr Alan Thompson
Andrew Nunn
Hilary Sanders
© CAMS Trial 2001
Background - Multiple Sclerosis
© CAMS Trial 2001
Background - MS
• 90% of patients with Multiple Sclerosis (MS) will experience symptoms of muscle spasticity and spasms.
• Current therapies for spasticity include baclofen, tizanidine, dantrolene and diazepam.
• All of these have significant side effects and limited efficacy.
© CAMS Trial 2001
Background - MS
• Cannabis - widespread anecdotal reports of beneficial effects on – spasticity– tremor– urinary disturbance– pain.
© CAMS Trial 2001
Background - MS
• Only two previous attempts at randomised double blind controlled studies of cannabinoids in total of 22 patients.
• Petro and Ellenberger, 1981– 9 patients, 3 days.– THC, double blinded crossover design– significant reduction in spasticity score.
© CAMS Trial 2001
Background - MS
• Ungerleider et al, 1988– 13 patients, up to 6 weeks– THC, double blinded crossover design– significant reduction in patient rating of
spasticity.
• Thus probably beneficial effect, but too small to generalise.
© CAMS Trial 2001
Background - Cannabis
© CAMS Trial 2001
Background - Cannabis
• Cannabis sativa - “Cultivated Cannabis”
• Many uses– Rope– Canvas– Clothing– Paper– Medicinal
© CAMS Trial 2001
Background - Cannabis
• Medicinal use for over 2000 years.
• First in the far east.
• Mentioned in western medical textbooks from the 13th century onwards.
• The peak in its use was in the 19th century.
© CAMS Trial 2001
Background - Cannabis
• Indications in 19th century. – Dysmenorrhoea
© CAMS Trial 2001
Background - Cannabis
• Other Indications. – Pain– Cramps– Fever– Vomiting– Asthma – Epilepsy.
© CAMS Trial 2001
Background - Cannabis
• Also psychoactive properties.
• Recreational use.
© CAMS Trial 2001
Background - Cannabis
• Fell out of use in early 20th century– concern over its recreational use – inconsistency in its preparation and absorption– poor storage stability
• Formally banned in 1928
• Remained prescribable until 1971.
© CAMS Trial 2001
Background - Cannabis
• Over 60 aromatic hydrocarbon compounds known as cannabinoids.
• Pharmacological effects mediated through cannabinoid receptors– CB1 receptors are found widely in the nervous
system– CB2 receptors predominantly on B
lymphocytes.
© CAMS Trial 2001
Background - Cannabis
• THC - most important active cannabinoid.
• Available synthetically.
• Prescribable for nausea as nabilone.
© CAMS Trial 2001
Background - Cannabis
• 1998 - House of Lords Select Committee report - “Cannabis, the scientific and medical evidence”.
• Positive about medicinal use.
• Advised further research before rescheduling of the drug.
© CAMS Trial 2001
Trial Design
© CAMS Trial 2001
Trial Design
• Multicentre randomised controlled trial.
• Comparing THC, cannabis oil and placebo.
• Coordinated from Plymouth– Derriford will recruit approximately 100
patients– 560 patients distributed across about 20 other
centres nationwide.
© CAMS Trial 2001
Trial Design - Centres
© CAMS Trial 2001
Trial Design
• Two Phases– Weeks 1-16
• All patients on drug
• Seven clinic visits
– Weeks 17-52• Patient chooses whether to continue drug
• Three clinic visits
© CAMS Trial 2001
Trial Design
Week Action1 – 5 Dose Titration to maximum tolerated
dose.6 - 14 Stable dose, assessment of
spasticity.15 Dose tailed off to zero16 Further spasticity assessment, patient
chooses whether to continuemedication
17-52 3 monthly assessments of spasticity,patient on or off medication aschosen at week 16
© CAMS Trial 2001
Primary Outcome Measures
• Ashworth Scale– 5 grade assessment of spasticity on clinical
examination.– Rather coarse steps.– Rather subjective.– Reasonable inter- and intra- rater reliability.
© CAMS Trial 2001
Secondary Outcome Measures
• Timed 10m walk
• Rivermead Mobility Index
• UK Neurological Disability Status Scale
• GHQ-30 (a quality of life questionnaire)
• Barthel Index (a measure of activities of daily living)
• 9 further category rating scales.
© CAMS Trial 2001
Blinding
• Risk of unblinding of patient due to widely known side effects.
• Two study personnel.– Treating physician– Assessor (physician or physiotherapist)
• Degree of unblinding assessed at the end of the trial.
© CAMS Trial 2001
Results
• Recruitment will start at beginning of 2001.
• Recruitment expected to last about 1 year.
• Results available 1 year after recruitment closes.
• Government has indicated that a successful trial may lead to rescheduling of cannabis.
© CAMS Trial 2001
Further Information
• References & general information:– www.cannabis-trial.plymouth.ac.uk
• email:– [email protected]
• Telephone:– 01752 315250