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To investigate the ability of Sativex to relieve central neuropathic pain in multiple sclerosis subjects.
Locally preserved from ClinicalTrials.govOpen ClinicalTrials.govlast source update 2023-01-10
What this record can show
Results are reported by the registry submitter and preserved exactly. They are not independent verification or a treatment recommendation.
Registry facts
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.
Linked local records
Local links use governed condition terms or exact source-reported intervention names. They are navigation candidates, not efficacy claims.
Interventions
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.
GW-1000-02Source-reported results
Results are reported by the registry submitter and preserved exactly. They are not independent verification or a treatment recommendation.
The average pain Numerical Rating Scale was completed at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your pain or average pain in the last 24 hours" where 0 = no pain and 10 = pain as bad as you can imagine. A negative value indicates an improvement in pain score from baseline.
Population: All patients who were randomised, received at least one actuation of study medication and had some on-treatment efficacy data were included in the analysis.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 33 | -2.7 | 1.91 |
| Placebo | 32 | -1.4 | 1.65 |
Each day patients were asked to record in their subject diary, whether or not they were "woken due to nerve pain last night", using a 0-10 Numerical Rating Scale sleep score where zero equated with "did not disrupt sleep" and 10 meant "completely disrupts sleep (unable to sleep due to pain)". A decrease in score from baseline indicates an improvement.
Eligibility
primary outcomes
Time frame: 0 - 4 weeks
The average pain Numerical Rating Scale was completed at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your pain or average pain in the last 24 hours" where 0 = no pain and 10 = pain as bad as you can imagine. A negative value indicates an improvement in pain score from baseline.
secondary outcomes
Time frame: 0 - 4 weeks
Each day patients were asked to record in their subject diary, whether or not they were "woken due to nerve pain last night", using a 0-10 Numerical Rating Scale sleep score where zero equated with "did not disrupt sleep" and 10 meant "completely disrupts sleep (unable to sleep due to pain)". A decrease in score from baseline indicates an improvement.
Time frame: 4 weeks
A 7-point Likert-type scale was used, with the question: 'Please assess the improvement in overall condition since the start of the study using the scale below' with the markers "very much improved, much improved, slightly improved, no change, slightly worse, much worse or very much worse". At Visit 2 (Baseline) patients wrote a brief description of their condition which was used at Week 4 to aid their memory regarding their symptoms at study start. For each of above markers the number of participants were reported.
Time frame: Baseline to end of treatment (0 - 4 weeks).
The Neuropathic Pain Scale score is the 0-100 sum of 10 individual pain scores (0-10 Numerical Rating Scale, 0= no pain to 10 = worst pain imaginable). A negative change from baseline indicates an improvement in pain.
Time frame: Baseline to end of study (0 - 4 weeks)
The Selective Reminding Test measures verbal learning and delayed recall through a multiple-trial list-learning paradigm. Patients are presented aurally with a list of 12 words for trial 1 and are asked to recall as many as possible. For trials 2-6, there is a selective presentation of only those words not recalled on the previous trial. Trial 7 is similar to the other trials but is assessed after an 11-minute delay. The score for the selective reminding test is the unweighted average of seven individual study results (min=0 and max=84) Higher scores indicate a better cognitive performance.
Publications
No exact PMID-linked public article is currently readable locally.
Population: All patients who were randomised, received at least one actuation of study medication and had some on-treatment efficacy data were included in the analysis.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 33 | -2.6 | 2.35 |
| Placebo | 32 | -0.8 | 1.79 |
A 7-point Likert-type scale was used, with the question: 'Please assess the improvement in overall condition since the start of the study using the scale below' with the markers "very much improved, much improved, slightly improved, no change, slightly worse, much worse or very much worse". At Visit 2 (Baseline) patients wrote a brief description of their condition which was used at Week 4 to aid their memory regarding their symptoms at study start. For each of above markers the number of participants were reported.
Population: All patients who were randomised, received at least one actuation of study medication and had some on-treatment efficacy data were included in the analysis.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 34 | 1 | - |
| Placebo | 32 | 0 | - |
| Sativex | 34 | 8 | - |
| Placebo | 32 | 4 | - |
| Sativex | 34 | 15 | - |
| Placebo | 32 | 6 | - |
| Sativex | 34 | 8 | - |
| Placebo | 32 | 19 | - |
| Sativex | 34 | 2 | - |
| Placebo | 32 | 3 | - |
| Sativex | 34 | 0 | - |
| Placebo | 32 | 0 | - |
| Sativex | 34 | 0 | - |
| Placebo | 32 | 0 | - |
The Neuropathic Pain Scale score is the 0-100 sum of 10 individual pain scores (0-10 Numerical Rating Scale, 0= no pain to 10 = worst pain imaginable). A negative change from baseline indicates an improvement in pain.
Population: All patients who were randomised, received at least one actuation of study medication and had some on-treatment efficacy data were included in the analysis.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 33 | -15.3 | 13.23 |
| Placebo | 32 | -8.1 | 14.60 |
The Selective Reminding Test measures verbal learning and delayed recall through a multiple-trial list-learning paradigm. Patients are presented aurally with a list of 12 words for trial 1 and are asked to recall as many as possible. For trials 2-6, there is a selective presentation of only those words not recalled on the previous trial. Trial 7 is similar to the other trials but is assessed after an 11-minute delay. The score for the selective reminding test is the unweighted average of seven individual study results (min=0 and max=84) Higher scores indicate a better cognitive performance.
Population: All patients who were randomised, received at least one actuation of study medication and had some on-treatment efficacy data were included in the analysis.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 33 | -0.9 | 10.52 |
| Placebo | 32 | 5.7 | 10.20 |
The 10/36 Spatial Recall Test assesses visual spatial learning and delayed recall. Patients are asked to view a 6 x 6 checkerboard with ten checkers for 10 seconds. They are then asked to recreate the pattern viewed on a blank checkerboard. The number of correct responses from three immediate trials and one delayed trial (7 minute delay) are recorded. The Total number of correct responses is the unweighted sum from the four trials. The score for the 10/36 spatial recall test was the unweighted average of four individual study results (min=0 and max=40). A higher score indicates better cognitive performance.
Population: All patients who were randomised, received at least one actuation of study medication and had some on-treatment efficacy data were included in the analysis.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 33 | 4.2 | 10.84 |
| Placebo | 30 | -1.5 | 8.91 |
The Symbol Digit Modalities Test measures complex attention and concentration in a task which also requires speed and accuracy in visual search and scanning. Patients are required to associate symbols with numbers and quickly generate the number when shown the symbol. The summary endpoint is the number of correct responses in 90 seconds. The symbol digit modalities test had a min of 0 and max score of 99. A higher score indicates better cognitive performance.
Population: All patients who were randomised, received at least one actuation of study medication and had some on-treatment efficacy data were included in the analysis.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 33 | 1.2 | 6.28 |
| Placebo | 32 | 3.67 | 4.64 |
The Paced Auditory Serial Addition Task assesses sustained attention and concentration. A pre-recorded tape is used to present two series of 60 numbers, one every 3 seconds and one every 2 seconds. Patients are asked to add each number to the one immediately preceding it and give the result. The task summary score is the percentage of correct answers is calculated. The PASAT score range was 0% to 100%. Higher scores indicate a better cognitive performance.
Population: All patients who were randomised, received at least one actuation of study medication and had some on-treatment efficacy data were included in the analysis.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 30 | 7.0 | 10.49 |
| Placebo | 30 | 6.6 | 7.89 |
Word list generation measures verbal associative fluency. Patients are given 60 seconds to give as many words beginning with a particular letter. The Total is the unweighted sum of all admissible words over three different trials. Higher scores indicate a better cognitive performance (min=0, max= not defined).
Population: All patients who were randomised, received at least one actuation of study medication and had some on-treatment efficacy data were included in the analysis.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 33 | 5.1 | 9.49 |
| Placebo | 32 | 2.9 | 10.66 |
The Guy's Neurological Disability Scale has 12 separate categories which include cognition, mood, vision, speech, swallowing, upper limb function, lower limb function, bladder function, bowel function, sexual function, fatigue, and 'others'. Each category consists of a series of questions, which are scored on a 0 to 5 scale, with 0 being indicative of a better outcome and 5 being indicative of a worse outcome. The total Guy's Neurological Disability Scale score is the unweighted sum from the 12 categories with a minimum score of 0 and maximum of 60. A negative value indicates an improvement in score from baseline.
Population: All patients who were randomised, received at least one actuation of study medication and had some on-treatment efficacy data were included in the analysis.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 34 | -1.5 | 4.45 |
| Placebo | 32 | -0.5 | 4.44 |
Intoxication levels were recorded on a Visual Analogue Scale, where zero equated with "no intoxication" and 100 equated with "extreme intoxication". A decrease in baseline score indicates a reduction in intoxication.
Population: All patients who were randomised, received at least one actuation of study medication and had some on-treatment efficacy data were included in the analysis.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 34 | 3.3 | 9.25 |
| Placebo | 32 | 0.3 | 0.97 |
Depression and anxiety was assessed using The Hospital Anxiety and Depression Scale. Seven of the items relate to anxiety and seven relate to depression. Each item on the questionnaire is scored from 0-3 giving a total score between 0 and 21 for either anxiety or depression. A reduction in score indicates an improvement. The change from baseline in the overall depression score at the end of treatment is presented.
Population: All patients who were randomised, received at least one actuation of study medication and had some on-treatment efficacy data were included in the analysis.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 34 | -0.1 | 2.92 |
| Placebo | 32 | -0.4 | 2.01 |
Depression and anxiety was assessed using The Hospital Anxiety and Depression Scale. Seven of the items relate to anxiety and seven relate to depression. Each item on the questionnaire is scored from 0-3 giving a total score between 0 and 21 for either anxiety or depression. A reduction in score indicates an improvement. The change from baseline in the overall anxiety score at the end of treatment is presented.
Population: All patients who were randomised, received at least one actuation of study medication and had some on-treatment efficacy data were included in the analysis.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 34 | -1.0 | 2.06 |
| Placebo | 32 | -0.5 | 2.45 |
The Multiple Sclerosis Functional Composite test is a three-part, standardized, quantitative, assessment instrument for use in clinical studies. The three components of the test measure leg function/ambulation, arm/hand function, and cognitive function. An increase in score indicates an improvement (range -3 to +3).
Population: All patients who were randomised, received at least one actuation of study medication and had some on-treatment efficacy data were included in the analysis.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 22 | 0.25 | 0.364 |
| Placebo | 21 | 0.19 | 0.174 |
The number of patients who experienced an adverse event during the course of the study is presented.
Population: All patients who were randomised, received at least one actuation of study medication and had some on-treatment efficacy data were included in the analysis.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Sativex | 34 | 30 | - |
| Placebo | 32 | 22 | - |
| Milestone | Sativex | Placebo |
|---|---|---|
| STARTED | 34 | 32 |
| COMPLETED | 32 | 32 |
| NOT COMPLETED | 2 | 0 |
| Event | System | Groups: affected / at risk |
|---|---|---|
| Dizziness | Nervous system disorders | Sativex: 18 / 34 · Placebo: 5 / 32 |
| Somnolence | Nervous system disorders | Sativex: 3 / 34 · Placebo: 0 / 32 |
| Disturbance in attention | Nervous system disorders | Sativex: 2 / 34 · Placebo: 0 / 32 |
| Hypoaesthesia | Nervous system disorders | Sativex: 2 / 34 · Placebo: 1 / 32 |
| Headache not otherwise specified | Nervous system disorders | Sativex: 1 / 34 · Placebo: 3 / 32 |
| Dissociation | Psychiatric disorders | Sativex: 3 / 34 · Placebo: 0 / 32 |
| Euphoric mood | Psychiatric disorders | Sativex: 2 / 34 · Placebo: 0 / 32 |
| Dry Mouth | Gastrointestinal disorders | Sativex: 4 / 34 · Placebo: 0 / 32 |
| Nausea | Gastrointestinal disorders | Sativex: 3 / 34 · Placebo: 2 / 32 |
| Glossodynia | Gastrointestinal disorders | Sativex: 0 / 34 · Placebo: 3 / 32 |
| Oral Pain | Gastrointestinal disorders | Sativex: 0 / 34 · Placebo: 3 / 32 |
| Fall | General disorders | Sativex: 3 / 34 · Placebo: 2 / 32 |
| Weakness | General disorders | Sativex: 2 / 34 · Placebo: 0 / 32 |
| Fatigue | General disorders | Sativex: 2 / 34 · Placebo: 2 / 32 |
| Migraine not otherwise specified | Nervous system disorders | Sativex: 0 / 34 · Placebo: 1 / 32 |
| Paraesthesia | Nervous system disorders | Sativex: 0 / 34 · Placebo: 1 / 32 |
| Diarrhoea not otherwise specified | Gastrointestinal disorders | Sativex: 2 / 34 · Placebo: 0 / 32 |
| Dyspepsia | Gastrointestinal disorders | Sativex: 0 / 34 · Placebo: 1 / 32 |
| Feeling drunk | General disorders | Sativex: 0 / 34 · Placebo: 1 / 32 |
| Application site burning | General disorders | Sativex: 0 / 34 · Placebo: 1 / 32 |
| Chest discomfort | General disorders | Sativex: 0 / 34 · Placebo: 1 / 32 |
| Urinary tract infection not otherwise specified | Infections and infestations | Sativex: 2 / 34 · Placebo: 1 / 32 |
| Nasopharyngitis | Infections and infestations | Sativex: 0 / 34 · Placebo: 2 / 32 |
| Otitis media not otherwise specified | Infections and infestations | Sativex: 0 / 34 · Placebo: 1 / 32 |
| Sinusitis not otherwise specified | Infections and infestations | Sativex: 0 / 34 · Placebo: 1 / 32 |
| Pharyngitis | Respiratory, thoracic and mediastinal disorders | Sativex: 2 / 34 · Placebo: 1 / 32 |
| Dyspnoea not otherwise specified | Respiratory, thoracic and mediastinal disorders | Sativex: 0 / 34 · Placebo: 1 / 32 |
| Gamma-glutamyltransferase increased | Investigations | Sativex: 0 / 34 · Placebo: 1 / 32 |
| Back pain | Musculoskeletal and connective tissue disorders | Sativex: 0 / 34 · Placebo: 1 / 32 |
| Diplopia | Eye disorders | Sativex: 0 / 34 · Placebo: 1 / 32 |
| Rash not otherwise specified | Skin and subcutaneous tissue disorders | Sativex: 0 / 34 · Placebo: 1 / 32 |
| Skin irritation | Skin and subcutaneous tissue disorders | Sativex: 0 / 34 · Placebo: 1 / 32 |
| Ligament sprain | Injury, poisoning and procedural complications | Sativex: 0 / 34 · Placebo: 1 / 32 |
| Breast pain | Reproductive system and breast disorders | Sativex: 0 / 34 · Placebo: 1 / 32 |
| White blood cell count increased | Investigations | Sativex: 2 / 34 · Placebo: 0 / 32 |
Time frame: Weeks 0 - 4
The 10/36 Spatial Recall Test assesses visual spatial learning and delayed recall. Patients are asked to view a 6 x 6 checkerboard with ten checkers for 10 seconds. They are then asked to recreate the pattern viewed on a blank checkerboard. The number of correct responses from three immediate trials and one delayed trial (7 minute delay) are recorded. The Total number of correct responses is the unweighted sum from the four trials. The score for the 10/36 spatial recall test was the unweighted average of four individual study results (min=0 and max=40). A higher score indicates better cognitive performance.
Time frame: 0 - 4 weeks
The Symbol Digit Modalities Test measures complex attention and concentration in a task which also requires speed and accuracy in visual search and scanning. Patients are required to associate symbols with numbers and quickly generate the number when shown the symbol. The summary endpoint is the number of correct responses in 90 seconds. The symbol digit modalities test had a min of 0 and max score of 99. A higher score indicates better cognitive performance.
Time frame: 0 - 4 weeks
The Paced Auditory Serial Addition Task assesses sustained attention and concentration. A pre-recorded tape is used to present two series of 60 numbers, one every 3 seconds and one every 2 seconds. Patients are asked to add each number to the one immediately preceding it and give the result. The task summary score is the percentage of correct answers is calculated. The PASAT score range was 0% to 100%. Higher scores indicate a better cognitive performance.
Time frame: 0 - 4 weeks
Word list generation measures verbal associative fluency. Patients are given 60 seconds to give as many words beginning with a particular letter. The Total is the unweighted sum of all admissible words over three different trials. Higher scores indicate a better cognitive performance (min=0, max= not defined).
Time frame: 0 - 4 weeks
The Guy's Neurological Disability Scale has 12 separate categories which include cognition, mood, vision, speech, swallowing, upper limb function, lower limb function, bladder function, bowel function, sexual function, fatigue, and 'others'. Each category consists of a series of questions, which are scored on a 0 to 5 scale, with 0 being indicative of a better outcome and 5 being indicative of a worse outcome. The total Guy's Neurological Disability Scale score is the unweighted sum from the 12 categories with a minimum score of 0 and maximum of 60. A negative value indicates an improvement in score from baseline.
Time frame: 0 - 4 weeks
Intoxication levels were recorded on a Visual Analogue Scale, where zero equated with "no intoxication" and 100 equated with "extreme intoxication". A decrease in baseline score indicates a reduction in intoxication.
Time frame: 0 - 4 weeks
Depression and anxiety was assessed using The Hospital Anxiety and Depression Scale. Seven of the items relate to anxiety and seven relate to depression. Each item on the questionnaire is scored from 0-3 giving a total score between 0 and 21 for either anxiety or depression. A reduction in score indicates an improvement. The change from baseline in the overall depression score at the end of treatment is presented.
Time frame: 0 - 4 weeks
Depression and anxiety was assessed using The Hospital Anxiety and Depression Scale. Seven of the items relate to anxiety and seven relate to depression. Each item on the questionnaire is scored from 0-3 giving a total score between 0 and 21 for either anxiety or depression. A reduction in score indicates an improvement. The change from baseline in the overall anxiety score at the end of treatment is presented.
Time frame: Baseline to end of treatment (0 - 4 weeks).
The Multiple Sclerosis Functional Composite test is a three-part, standardized, quantitative, assessment instrument for use in clinical studies. The three components of the test measure leg function/ambulation, arm/hand function, and cognitive function. An increase in score indicates an improvement (range -3 to +3).
Time frame: 0 - 4 weeks
The number of patients who experienced an adverse event during the course of the study is presented.