Transcript the Presentation

CAMS Study
A Multicentre Randomised
Controlled Trial of Cannabinoids in
Multiple Sclerosis
Principle Investigators
Dr 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
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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
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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.
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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
1–5
6 - 14
15
16
17-52
Action
Dose Titration to maximum tolerated
dose.
Stable dose, assessment of
spasticity.
Dose tailed off to zero
Further spasticity assessment, patient
chooses whether to continue
medication
3 monthly assessments of spasticity,
patient on or off medication as
chosen 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
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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
© CAMS Trial 2001