Pilot study of smoked cannabis for chronic neuropathic pain

ISRCTN	ISRCTN68314063
DOI	https://doi.org/10.1186/ISRCTN68314063
Protocol serial number	JHM-50014
Sponsor	Montreal General Hospital (Canada)
Funder	Canadian Institutes of Health Research (CIHR - http://www.cihr-irsc.gc.ca)/Health Canada (HC) Medical Marijuana Research Programme (Canada)

Submission date: 11/10/2005
Registration date: 21/06/2006
Last edited: 10/11/2010

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nervous System Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Mark Ware
Scientific

McGill University Health Centre
Pain Centre
Montreal General Hospital
Room E19-145
1650 Cedar Avenue
Montreal
H3G 1A4
Canada

Phone	+1 514 934 1934 ext 42784
Email	mark.ware@muhc.mcgill.ca

Study information

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
Scientific title	Smoked cannabis for chronic neuropathic pain: a randomised controlled trial
Study objectives	The principle hypothesis of this study is that smoked cannabis containing 9.43% tetrahydrocannabinol (THC) is superior to that containing 0% THC in reducing pain intensity over a five day period, in patients with moderate to severe neuropathic pain. Please note that this trial record was updated on the 18th January 2008 due to a protocol amendment which took place on the 8th February 2006. All changes to this trial record are entered under the date 18/01/2008.
Ethics approval(s)	Research Ethics Committee, McGill University Health Science Centre-Montreal General Hospital, Montreal, Quebec, Canada approved on 9th January 2002). Updated as of 18/01/2008: Full board approval for amendments were received on the 28th March 2006. However, please note that no patients were recruited on the amended protocol.
Health condition(s) or problem(s) studied	Chronic neuropathic pain
Intervention	Cannabis containing 9.43% THC versus cannabis containing 0% THC. Please note that the date of the last follow-up of the last recruited trial participant was 9th March 2006.
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Cannabis
Primary outcome measure(s)	1. Average pain intensity measured daily during each cycle by 100 mm visual analogue scale (VAS) 2. No pain and worst pain possible will be used as anchors in the 11-item numerical rating scale. The daily pain intensity score will be averaged across all study days for each cycle to comprise the main outcome variable.
Key secondary outcome measure(s)	The main clinical outcomes will be the subjective 'high', mood, quality of life, and quality of sleep. Treatment discernment will be assessed by potency assessments at inpatient and follow up visits: 1. Trial feasibility: practical issues of recruitment and compliance will be recorded during the study 2. Pain quality: the McGill Pain Questionnaire (MPQ) measures affective and cognitive aspects of pain experience at patient visits. This will be administered on day five of each of the four five-day treatment cycles. 3. Sleep: a modification of the Leeds Sleep Evaluation Questionnaire (LSEQ) will be used. This will be administered by daily telephone interviews during each treatment cycle. 4. Mood: the short form Profile of Mood States (POMS) will be administered on day five of each of the four five-day treatment cycles 5. Quality of life: quality of life will be assessed using the EuroQOL 5D instrument, which will be administered on day five of each of the four five-day treatment cycles 6. Physiological assessments: physiological measurements (blood pressure, heart rate, electrocardiogram [ECG] changes, pulse oximetry, respiratory rate) will be conducted at 15 minute intervals during the first hour and hourly for two hours after smoking on day one of each treatment cycle 7. Quantitative sensory testing (QST): QST of cutaneous thermal sensitivity will be performed at baseline (during the screening visit) and on day five of each of the four five-day treatment cycles 8. 'High': will be measured subjectively at 15 minute intervals during the first hour and hourly for two hours after smoking on day one of each treatment cycle using an unmarked VAS scale (anchors: 0 is not at all, 10 is extremely) 9. Other subjective effects: the subjects will be asked to identify their current level of 'relaxed', 'stressed', 'happy' measured subjectively at 15 minute intervals during the first hour and hourly for two hours after smoking on day one of each treatment cycle using 100 mm VAS scales using the anchors 'not at all' and 'extremely' 10. Potency assessments: the patients ability to detect the strength of each cannabis preparation administered will be tested using subjective potency assessments. This will be administered on day one and day five of each treatment cycle.
Completion date	31/01/2006

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	32
Key inclusion criteria	Current inclusion criteria as of 18/01/2008: 1. Ambulatory, otherwise healthy, men and women with neuropathic pain of at least three months duration which is due to trauma or surgery, with clinical evidence of allodynia or hyperalgesia 2. Average weekly pain intensity score less than or equal to 4 on a 10 cm visual analogue scale (anchors: 0 is no pain, 10 is worst pain ever) 3. Stable analgesic regimen (no anticipated change in therapy over the next two months) 4. No cannabis use in the past month 5. Ability to comply with smoking procedure 6. 18 years and older 7. Ability to attend research centre twice weekly for four weeks over a two month period, and to be able to be contacted by telephone during the study period 8. Normal liver (aspartate aminotransferase [AST] less than 3 x normal) and renal function (serum creatinine less than 133 µmol/l) 9. Haematocrit greater than 35% 10. Negative serum beta human chorionic gonadotrophin [ßhCG] pregnancy test 11. Women of childbearing potential should use adequate contraception during study and for three months after study 12. Proficient in English or French 13. Willing and able to give written informed consent Previous inclusion criteria: 1. Ambulatory, otherwise healthy, men and women with neuropathic pain of at least three months duration which is due to trauma or surgery, with clinical evidence of allodynia or hyperalgesia 2. Average weekly pain intensity score 5≤ on a 10 cm visual analogue scale (anchors: 0 is no pain, 10 is worst pain ever) 3. Stable analgesic regimen (no anticipated change in therapy over the next two months) 4. No cannabis use in the past month 5. Ability to comply with smoking procedure 6. 18 years and older 7. Ability to attend research centre twice weekly for four weeks over a two month period, and to be able to be contacted by telephone during the study period 8. Normal liver (aspartate aminotransferase [AST] <3 x normal) and renal function (serum creatinine <133 µmol/l) 9. Haematocrit >38% 10. Negative serum beta human chorionic gonadotrophin [ßhCG] pregnancy test 11. Women of childbearing potential should use adequate contraception during study and for three months after study 12. Proficient in English or French 13. Willing and able to give written informed consent
Key exclusion criteria	Current exclusion criteria as of 18/01/2008: 1. Positive results of cannabinoid screening 2. Pain due to cancer or nociceptive causes (e.g. acute trauma, herpes zoster) 3. Unstable heart disease such as arrhythmias, cardiac failure, ischaemic heart disease, hypertension 4. Current substance abuse/dependence (including cannabis) as defined by the Diagnostic and Statistical Manual of mental disorders fourth edition (DSM IV) criteria 5. Unstable or untreated lung disease (tuberculosis [TB], asthma, carcinoma, chronic obstructive pulmonary disease [COPD]) 6. History of uncontrolled psychotic disorder in the past year (for example, schizophrenia or bipolar disorder) 7. Current suicidal ideation, as assessed by clinical psychologist 8. Pregnancy and/or breast-feeding 9. Participation in other clinical trial in the 30 days prior to enrolment 10. Ongoing medical insurance or compensation claims (may confound subjective pain intensity ratings if pain has possible secondary gain) Previous exclusion criteria: 1. Positive results of cannabinoid screening 2. Pain due to cancer or nociceptive causes (e.g. acute trauma, herpes zoster) 3. Cardiac arrhythmias, cardiac failure, ischaemic heart disease 4. Current substance abuse/dependence (including cannabis) as defined by the Diagnostic and Statistical Manual of mental disorders fourth edition (DSM IV) criteria 5. Pulmonary complications (tuberculosis [TB], asthma, carcinoma, chronic obstructive pulmonary disease [COPD]) 6. History of psychotic disorder (for example, schizophrenia or bipolar disorder) 7. Current suicidal ideation, as assessed by clinical psychologist 8. Pregnancy and/or breast-feeding 9. Participation in other clinical trial in the 30 days prior to enrolment 10. Ongoing medical insurance or compensation claims (may confound subjective pain intensity ratings if pain has possible secondary gain)
Date of first enrolment	01/08/2003
Date of final enrolment	31/01/2006

Locations

Countries of recruitment

Canada

Study participating centre

McGill University Health Centre

Montreal
H3G 1A4
Canada

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	05/10/2010		Yes	No