Clinical trial NCT01610700: An Investigation of Delta-9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) in Multiple Sclerosis Patients
Official title: Double Blind, Randomised, Parallel Group, Placebo Controlled Trial of a Combination of THC and CBD in Patients With Multiple Sclerosis, Followed by an Open Label Assessment and Study Extension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Sclerosis
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2012-06-04
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A study to compare the efficacy of GW-1000-02 \[named Sativex® in Canada and also named Sativex® Oromucosal Spray\] with placebo in relieving five key symptoms of Multiple Sclerosis after six weeks of therapy.

Detailed description: Eligible subjects entered a one to two week baseline period; followed by a six week double blind, randomised, parallel group comparison of GW-1000-02 with placebo, self-titrated to symptom resolution or maximum tolerated dose. Existing medication continued at a constant dose.

Primary efficacy comparisons were made between symptom scores recorded during baseline and scores recorded at the end of the parallel group period.

Eligibility criteria: Inclusion Criteria:

* Aged at least 18 years.
* Multiple Sclerosis of any type.
* Stable Multiple Sclerosis symptomatology during the four weeks before study entry.
* Symptoms of the required severity (\>50 mm on a 100 mm Visual Analogue Scale severity scale) in least one of the specified impairment categories; spasticity, muscle spasms, disturbed bladder control, neuropathic pain, limb tremor.
* A stable medication regime during the four weeks before study entry.
* Willing to abstain from cannabis or cannabinoids for at least seven days before study entry, and during the study.
* Agreed either to use effective contraception during the study and for three months thereafter, or had been surgically sterilised or, if female, were post-menopausal.
* Clinically acceptable laboratory results for pre-study screening.
* Willing and able to undertake and comply with all study requirements.
* Willing and able to read, consider and understand the subject information and consent form and give written informed consent. Subjects unable to read or to sign the document procedures were treated as detailed in the Declaration of Helsinki.
* Willing for their general practitioner, and consultant if appropriate, to be informed of study participation.
* Willing for their name to be notified to Home Office for participation in the study.

Exclusion Criteria:

* Known or strongly suspected to be abusing drugs, including alcohol.
* Not prepared to abstain from cannabis or cannabinoids during the study.
* Current or past addiction to cannabis.
* Known or suspected to have had an adverse reaction to cannabinoids causing psychosis or other severe psychiatric illness.
* History of any type of schizophrenia, any other psychotic illness, or other significant psychiatric illness or personality disorder other than depression associated with chronic illness.
* Received any drug containing levodopa (Sinemet®, Sinemet plus®, Levodopa®, L-dopa®, Madopar®, Benserazide®).
* Serious cardiovascular disorder including angina, uncontrolled hypertension, or an uncontrolled symptomatic cardiac arrhythmia.
* Significant renal or hepatic impairment as shown in medical history or indicated by laboratory results.
* History of epilepsy.
* Terminal illness or other condition in which placebo medication would be inappropriate.
* Pregnant, lactating or at risk of pregnancy.
* Participated in any other clinical research study during the 12 weeks before study entry.
* Planned hospital admission between study entry and Visit 6.
* Planned travel outside the UK between study entry and Visit 6.

Primary outcomes:
measure: Change From Baseline in Composite Primary Impairment Visual Analogue Scale Score at the End of 6 Weeks of Treatment
timeFrame: baseline and 6 weeks
Secondary outcomes:
measure: Change From Baseline in Spasticity Visual Analogue Scale Score at the End of 6 Weeks of Treatment
timeFrame: baseline and 6 weeks
measure: Change From Baseline in Pain Visual Analogue Scale Score at the End of 6 Weeks of Treatment
timeFrame: baseline and 6 weeks
measure: Change From Baseline in Muscle Spasm Visual Analogue Scale Score at the End of 6 Weeks of Treatment
timeFrame: baseline and 6 weeks
measure: Change From Baseline in Tremor Visual Analogue Scale Score at the End of 6 Weeks of Treatment
timeFrame: baseline and 6 weeks
measure: Change From Baseline in Bladder Problems Visual Analogue Scale Score at the End of 6 Weeks of Treatment
timeFrame: baseline and 6 weeks
measure: Subject Global Opinion of Effect on Multiple Sclerosis at the End of Treatment
timeFrame: 6 weeks
measure: Change From Baseline in Modified Ashworth Scale Score at the End of Treatment
timeFrame: baseline and 6 weeks
measure: Change From Baseline in the Mean Beck's Depression Inventory (BDI-II) Score at the End of Treatment
timeFrame: baseline and 6 weeks
measure: Change From Baseline in the Mean Fatigue Severity Scale Questionnaire Score at the End of Treatment
timeFrame: baseline and 6 weeks
measure: Change From Baseline in the Mean Rivermead Mobility Index Score at the End of Treatment
timeFrame: Baseline and 6 weeks
measure: Change From Baseline in the Mean Total 28-item General Health Questionnaire Score at the End of Treatment
timeFrame: baseline and 6 weeks
measure: Change From Baseline in the Mean Nine-hole Peg Test Score at the End of Treatment
timeFrame: baseline and 6 weeks
measure: Change From Baseline in the Mean Total Bladder Control Test Score at the End of Treatment
timeFrame: baseline and 6 weeks
measure: Change From Baseline in the Mean Tremor Activities of Daily Living Scale Score at the End of Treatment
timeFrame: baseline and 6 weeks
measure: Change From Baseline in the Mean Ten-metre Mobility Score at the End of Treatment
timeFrame: baseline and 6 weeks
measure: Change From Baseline in the Mean Sleep Quality 100 mm Visual Analogue Scale Score at the End of Treatment
timeFrame: baseline and 6 weeks
measure: Change From Baseline in the Mean Sleep Amount 100 mm Visual Analogue Scale Score at the End of Treatment
timeFrame: Baseline and 6 weeks
measure: Change From Baseline in the Mean Feeling Upon Wakening 100 mm Visual Analogue Scale Score at the End of Treatment
timeFrame: baseline and 6 weeks
measure: Change From Baseline in the Mean Barthel Activities for Daily Living Scale Score at the End of Treatment
timeFrame: baseline and 6 weeks
measure: Change From Baseline in the Mean Short Orientation-Memory-Concentration Test at the End of Treatment
timeFrame: baseline and 6 weeks
measure: Change From Baseline in the Mean Reading Visual Acuity Test Score at the End of Treatment
timeFrame: baseline and 6 weeks
measure: Change From Baseline in the Mean Care-Giver Strain Index Score at the End of Treatment
timeFrame: baseline and 6 weeks
measure: Change From Baseline in the Mean Guy's Neurological Disability Scale Score at the End of Treatment
timeFrame: baseline and 6 weeks
measure: Change From Baseline in the Mean Total Adult Memory and Information Processing Battery Test Score at the End of Treatment
timeFrame: baseline and 6 weeks
Other outcomes:
Locations:
city: Oxford
country: United Kingdom
facility: Rivermead Rehabilitation Centre
Study officials:
References:
citation: Wade DT, Makela P, Robson P, House H, Bateman C. Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients. Mult Scler. 2004 Aug;10(4):434-41. doi: 10.1191/1352458504ms1082oa.