Clinical trial NCT01604265: A Study of Sativex in the Treatment of Central Neuropathic Pain Due to Multiple Sclerosis
Official title: A Double Blind, Randomised, Parallel Group, Placebo Controlled Study of Sativex in the Treatment of Central Neuropathic Pain in Multiple Sclerosis.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Sclerosis
Neuropathic Pain
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2012-05-23
Enrollment: 66
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: To investigate the ability of Sativex to relieve central neuropathic pain in multiple sclerosis subjects.

Detailed description: Multiple sclerosis subjects with a clinical diagnosis of central neuropathic pain entered a seven to ten day baseline period, followed by a four week double blind, randomised, parallel group comparison of Sativex, with placebo. The study medication was self-titrated to symptom resolution or maximum tolerated or allowed dose. Visits occurred at the end of weeks one and four (end of the study) or earlier if they withdrew. A follow-up visit occurred 30 - 40 days after completion or withdrawal.

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.

Primary outcomes:
measure: Change From Baseline in the Mean Pain 0-10 Numerical Rating Scale Score at the End of Treatment (4 Weeks)
timeFrame: 0 - 4 weeks
Secondary outcomes:
measure: Change From Baseline in the Mean 0-10 Numerical Rating Scale Sleep Score at the End of Treatment (4 Weeks)
timeFrame: 0 - 4 weeks
measure: Subject Global Impression of Change at Week 4
timeFrame: 4 weeks
measure: Change From Baseline in the Mean Neuropathic Pain Scale 0-10 Numerical Rating Scale Score at the End of Treatment (Week 4)
timeFrame: Baseline to end of treatment (0 - 4 weeks).
measure: Change From Baseline in the Mean Brief Repeatable Battery of Neuropsychological Test Score for 'Selective Reminding' at the End of Treatment (Week 4)
timeFrame: Baseline to end of study (0 - 4 weeks)
measure: Change From Baseline in the Mean Brief Repeatable Battery of Neuropsychological Test Score for '10/36 Spatial Recall' at the End of Treatment (Week 4)
timeFrame: Weeks 0 - 4
measure: Change From Baseline in the Mean Brief Repeatable Battery of Neuropsychological Test Score for 'Symbol Digit Modalities' at the End of Treatment (Week 4)
timeFrame: 0 - 4 weeks
measure: Change From Baseline in the Mean Brief Repeatable Battery of Neuropsychological Test Score for the 'Paced Auditory Serial Addition Task' (PASAT) at the End of Treatment (Week 4)
timeFrame: 0 - 4 weeks
measure: Change From Baseline in the Mean Brief Repeatable Battery of Neuropsychological Test Score for 'Word List Generation' at the End of Treatment (4 Weeks)
timeFrame: 0 - 4 weeks
measure: Change From Baseline in the Mean Total Guy's Neurological Disability Scale Score at the End of Treatment (4 Weeks)
timeFrame: 0 - 4 weeks
measure: Change From Baseline in the Mean 0-100 mm Visual Analogue Scale Score for Intoxication Levels at the End of Treatment (4 Weeks)
timeFrame: 0 - 4 weeks
measure: Change From Baseline in The Hospital Anxiety and Depression Scale Score for Depression at the End of Treatment (4 Weeks)
timeFrame: 0 - 4 weeks
measure: Change From Baseline in The Hospital Anxiety and Depression Scale Score for Anxiety at the End of Treatment (4 Weeks)
timeFrame: 0 - 4 weeks
measure: Change From Baseline in the Multiple Sclerosis Functional Composite Score at the End of Treatment (4 Weeks)
timeFrame: Baseline to end of treatment (0 - 4 weeks).
measure: Incidence of Adverse Events as a Measure of Patient Safety.
timeFrame: 0 - 4 weeks
Other outcomes:
Locations:
city: Liverpool
country: United Kingdom
facility: Walton Centre for Neurology and Neurosurgery
Study officials:
References:
citation: Rog DJ, Nurmikko TJ, Friede T, Young CA. Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis. Neurology. 2005 Sep 27;65(6):812-9. doi: 10.1212/01.wnl.0000176753.45410.8b.