© 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:– cannabis-trial@plymouth.ac.uk

• Telephone:– 01752 315250