A Study of Sativex in the Treatment of Central Neuropathic Pain Due to Multiple Sclerosis
Condition: Multiple Sclerosis; Neuropathic Pain
MeSH terms: Multiple Sclerosis; Neuralgia; Sclerosis
Intervention: Placebo; Sativex
Intervention description: Contained peppermint oil, 0.05% (v/v), quinoline yellow, 0.005% (w/v), sunset yellow, 0.0025% (w/v), in ethanol:propylene glycol (50:50) excipient. Each actuation delivered 100 μl. The maximum permitted dose of study medication was eight actuations in any three hour period, and 48 actuations in any 24 hour period.; Contained delta-9-tetrahydrocannabinol (THC), (25 mg/ml):cannabidiol (CBD), (25 mg/ml) as extract of Cannabis sativa L., with peppermint oil, 0.05% (v/v), in ethanol:propylene glycol (50:50) excipient. Each actuation delivered 100 μl (THC 2.5 mg and CBD 2.5 mg). The maximum permitted dose of study medication was eight actuations in any three hour period, and 48 actuations in any 24 hour period.
Intervention MeSH terms: Nabiximols
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 66.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      To investigate the ability of Sativex to relieve central neuropathic pain in multiple
      sclerosis subjects.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Willing and able to give informed consent for participation in the study.

          -  Male or female subjects aged 18 years or above.

          -  Diagnosed with any disease sub-type of multiple sclerosis, with relapses/remission not
             expected to influence neuropathic pain.

          -  Duration of multiple sclerosis greater than six months.

          -  Central neuropathic pain, due to multiple sclerosis, of at least three months
             duration, for which a nociceptive, peripheral neuropathic or psychogenic cause
             appeared unlikely and was expected to remain stable for the duration of the study.

          -  Pain score with a severity of four or more on at least four completed Numerical Rating
             Scale scores in the baseline week.

          -  Regular medication regime for neuropathic pain had been stable during the previous two
             weeks, prior to reduction of tricyclic antidepressants, if applicable.

          -  Willing to reduce the dosage of amitriptyline, or equivalent of other tricyclic
             antidepressants, to a maximum of 75 mg per day, if applicable.

          -  No cannabinoid use (cannabis, Marinol or Nabilone) at least seven days before study
             entry and willing to abstain from any use of cannabis during the study.

          -  Female subjects of child bearing potential or male subjects whose partner was of child
             bearing potential, who were willing to ensure that they or their partner used
             effective contraception during the study and for three months thereafter.

          -  Able (in the investigators opinion) and willing to comply with all study requirements.

          -  Willing for his or her name to be notified to the Home Office for participation in
             this study.

          -  Willing for his or her general practitioner and consultant, if appropriate, to be
             notified of participation in the study.

        Exclusion Criteria:

          -  History of schizophrenia, other psychotic illness, severe personality disorder or
             other significant psychiatric disorder other than depression associated with their
             underlying condition.

          -  Concomitant severe non-neuropathic pain or the presence of illness such as diabetes
             mellitus that could have caused peripheral neuropathic pain.

          -  Known or strongly suspected alcohol or substance abuse or considered to be at risk of
             alcohol or substance abuse by the investigator.

          -  Severe cardiovascular disorder, such as ischaemic heart disease, arrhythmias (other
             than well controlled atrial fibrillation), poorly controlled hypertension or severe
             heart failure.

          -  History of epilepsy or convulsions.

          -  Significant renal or hepatic impairment as shown in medical history or indicated by
             clinical laboratory results from samples taken at baseline.

          -  Elective surgery or other procedures requiring general anaesthesia scheduled during
             the study.

          -  Terminal illness.

          -  Any other significant disease or disorder which, in the opinion of the Investigator,
             could either have put the subject at risk because of participation in the study, or
             influenced the result of the study, or the subject's ability to participate in the
             study.

          -  Female subjects who were pregnant, lactating or planning pregnancy during the course
             of the study.

          -  Regular levodopa (Sinemet, Sinemet Plus, Levodopa, L-dopa, Madopar, Benserazide)
             therapy within seven days of study entry.

          -  Known or suspected hypersensitivity to cannabinoids or any of the excipients of the
             study medications.

          -  Known or suspected adverse reaction to cannabinoids.

          -  Travel outside the UK planned during study.

          -  Donation of blood during the study.

          -  Participated in any other pharmacological clinical research study within 30 days of
             study entry.

          -  Previously enrolled into this study.