Trial registered on ANZCTR


Trial ID
ACTRN12611000398909
Ethics application status
Approved
Date submitted
12/04/2011
Date registered
15/04/2011
Type of registration
Prospectively registered

Titles & IDs
Public title
Double blind, randomised, placebo controlled trial of Sativex for the management of cannabis withdrawal
Scientific title
Double blind, randomised, placebo controlled trial of Sativex for the management of cannabis withdrawal
Secondary ID [1] 259990 0
Nil
Universal Trial Number (UTN)
U1111-1120-7086
Trial acronym

Health condition
Health condition(s) or problem(s) studied:
Cannabis withdrawal 265620 0
Condition category
Condition code
Public Health 265768 265768 0 0
Health service research
Mental Health 265781 265781 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Investigational drug: Sativex (1 spray: 2.7 mg THC and 2.5 mg CBD) in an alcohol and peppermint oil liquid administered as an oromucosal spray onto the inside of the mouth (but not intended to be swallowed and digested through the stomach - so some time (1 minute) should be taken after each single spray is administered to ensure absorption, before the next spray is administered). The patient cannot choose when they receive their 8 spray dose, they must have them all at the 6 hourly interval.

Dosage form/strength: maximum 800 uL every six hours (X8 sprays every six hours). Participants may not take partial doses (i.e. 6 sprays) but they can ask to miss up to two of the 6 hourly dose in a day. Patients are in hospital for 8 nights, discharging on day 9.
Intervention code [1] 264405 0
Treatment: drugs
Comparator / control treatment
Placebo spray - comprising alcohol and peppermint oil
Control group
Placebo

Outcomes
Primary outcome [1] 266522 0
Self-reported measures of cannabis withdrawal using the Cannabis Withdrawal Scale (a modified version of the MWC (Budney et al., 1999)).
Timepoint [1] 266522 0
Four times a day for 9 days (6am, 11 am, 6pm and 10pm)
Primary outcome [2] 266523 0
Treatment completion, defined as completing 9 days of inpatient treatment under protocol conditions (categorical yes/no); and number of days of inpatient treatment completed (range: 0-9).
Timepoint [2] 266523 0
Quantified once on day of patient discharge from hospital
Primary outcome [3] 266524 0
Adverse events during the inpatient treatment period using a tailor made Adverse Events Checklist and administered by clinician/nurse/medical officer. Adverse events may include any of the following: Dizziness, Dry mouth, Tachycardia, Stomache ache, Slowed motor skills, slowed reaction time, anxiety, dysphoria, paranoia, oro-mucosal ulceration. Adverse events will be rated on a 0 - 3 scale, 0 being None, 1 being Mild, 2 being Moderate, 3 being Severe.
Timepoint [3] 266524 0
Once daily for the 9 days of inpatient stay
Secondary outcome [1] 273957 0
Self-reported cannabis use with total days used cannabis (range 0-28) and longest period of continuous abstinence (range 0-28) during the one month follow-up period (quantifying rates of continuous and point prevalence abstinence from cannabis, time to relapse, levels of cannabis use, and cannabis related problems at follow up), using the Timeline Followback method
Timepoint [1] 273957 0
At baseline (day 1 of entry into inpatient unit) for the previous 28 days, and at follow up (28 days after discharge from hospital)
Secondary outcome [2] 273958 0
Urine Carboxy-THC: creatinine ratio using Gas Chromatography/Mass Spectrometry
Timepoint [2] 273958 0
At baseline (day 1 of entry into inpatient unit), daily during 9 day inpatient stay and at follow up (28 days after discharge from hospital)
Secondary outcome [3] 273959 0
Blood plasma profiles of cannabinoid metabolites (THC and its primary metabolite (THC-COOH) to CBD and its primary metabolite (CBD-7-oic acid))
Timepoint [3] 273959 0
Day 1 of intake to the inpatient unit(pre-sativex). And the same measures taken after Sativex has been administered to participants (taken on days 3 and 7).
Secondary outcome [4] 273960 0
Cannabis Problems Questionnaire (Copeland, Gilmour, Gates, & Swift, 2005)
Timepoint [4] 273960 0
Baseline (Day 1) and Follow up (28 days after discharge)
Secondary outcome [5] 273961 0
Brief Treatment Outcome Measure-Social Functioning Scale (Lawrinson, Copeland, & Indig, 2005)
Timepoint [5] 273961 0
Baseline (Day 1) and Follow up (28 days after discharge)
Secondary outcome [6] 273962 0
Insomnia severity index (Bastien, Vallieres, & Morin, 2001)
Timepoint [6] 273962 0
Baseline (Day 1), Discharge (Day 9) and Follow up (28 days after discharge)
Secondary outcome [7] 273963 0
Cannabis Dependence using the Severity of Dependence Scale (SDS) (Martin, Copeland, Gates, & Gilmour, 2006; Swift, Copeland, & Hall, 1998)
Timepoint [7] 273963 0
Baseline (Day 1), Discharge (Day 9) and Follow up (28 days after discharge)
Secondary outcome [8] 273964 0
Depression, Anxiety and Stress measures using the 21 item version of the Depression, Anxiety and Stress Scale (Lovibond & Lovibond, 1995)
Timepoint [8] 273964 0
Baseline (Day 1), Discharge (Day 9) and Follow up (28 days after discharge)
Secondary outcome [9] 273965 0
Quality of life using the Sheehan Disability Scale
Timepoint [9] 273965 0
Baseline (Day 1) and Follow up (28 days after discharge)
Secondary outcome [10] 273966 0
Self efficacy for Quitting Cannabis Questionnaire
Timepoint [10] 273966 0
Baseline (Day 1), Discharge (Day 9) and Follow up (28 days after discharge)
Secondary outcome [11] 273967 0
Anxiety Sensitivity Index
Timepoint [11] 273967 0
Baseline (Day 1) and Follow up (28 days after discharge)
Secondary outcome [12] 273968 0
Distress tolerance Scale
Timepoint [12] 273968 0
Baseline (Day 1) and Follow up (28 days after discharge)

Eligibility
Key inclusion criteria
1. Between 18-65 years of age (Both males and females)
2. Regular recent cannabis use (average of 5 times per week – self report)
3. Meet DSM-IV-TR 'Registered Trademark' criteria for cannabis dependence
4. Has made unsuccessful quit attempts in the past
5. Desire to give up cannabis
6. Prepared to enter a hospital ward for 9 days

If NO to any (1 - 6) client is not eligible for SATIVEX trial phone screen, provide usual referral/treatment advice.
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. More than twice weekly use of an illicit drug in the last 30 days (other than cannabis)
2. Dependence on a substance other than cannabis and tobacco
3. Pregnant or breastfeeding
4. Female of child bearing potential NOT using contraception
5. Evidence of severe medical impairment (e.g. chronic pain, severe hepatic impairment or cardiovascular disease)
6. Evidence of severe cognitive or psychiatric impairment (e.g. bipolar, schizophrenia, suicidal ideation)
7. Current (within past month) prescription for antipsychotic or mood stabilising medications
8. Currently prescribed warfarin
9. Allergy to cannabinoids, propylene glycol, ethanol or peppermint oil
10. Not English literate
11. Specialist substance use treatment in the last 30 days

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation involves contacting the holder of the allocation schedule who was "off-site" or at central administration
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Participants receive either Sativex or Placebo - never both, and participants are anticipated to come into the study one at a time (at each of the two study sites)
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy

Recruitment
Anticipated date of first participant enrolment
31/07/2011
Actual date of first participant enrolment
Anticipated date last participant enrolled
Actual date last participant enrolled
Target sample size
50
Actual sample size
Recruitment status
Not yet recruiting
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 3921 0
2000
Recruitment postcode(s) [2] 3922 0
2300

Funding & Sponsors
Funding source category [1] 264870 0
Government body
Name [1] 264870 0
National Health and Medical Research Council
Address [1] 264870 0
Level 1
16 Marcus Clarke Street
Canberra ACT 2601
Country [1] 264870 0
Australia
Primary sponsor type
University
Name
University of New South Wales
Address
The University of New South Wales
SYDNEY
NSW 2052
AUSTRALIA
Country
Australia
Secondary sponsor category [1] 263971 0
None
Name [1] 263971 0
Address [1] 263971 0
Country [1] 263971 0
Other collaborator category [1] 251941 0
Hospital
Name [1] 251941 0
Belmont District Hospital
Address [1] 251941 0
Croudace Bay Road, Belmont NSW 2280
Country [1] 251941 0
Australia
Other collaborator category [2] 251942 0
Hospital
Name [2] 251942 0
Sydney & Sydney Eye Hospital
Address [2] 251942 0
GPO Box 1614, Sydney NSW 2001 Australia
Country [2] 251942 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 266831 0
Hunter New England Research Ethics Committee
Ethics committee address [1] 266831 0
Locked Bag No 1
New Lambton, NSW 2305
Ethics committee country [1] 266831 0
Australia
Date submitted for ethics approval [1] 266831 0
Approval date [1] 266831 0
02/02/2011
Ethics approval number [1] 266831 0
10/12/15/3.02

Summary
Brief summary
The primary objective of the study is to examine the safety and efficacy of SATIVEX 'Registered Trademark (R)' in the inpatient management of cannabis withdrawal, in a double blinded randomised trial compared to placebo. Specifically, the study will compare withdrawal severity, detoxification completion and adverse events between the two conditions in an intention-to-treat analysis. Secondary objectives include 1-month post-withdrawal outcomes (including cannabis and other drug use and psychosocial outcomes), and to assess the relationship between the number, severity and duration of cannabis withdrawal symptoms and rates of continuous and point prevalence abstinence from cannabis, time to relapse, levels of cannabis use, and cannabis related problems at one month follow-up. The study will also explore the cognitive impact of withdrawing from cannabis, as well as the impact of SATIVEX on cognitive functioning, with an aim to assessing the real world safety profile of the drug ahead of larger outpatient studies. The study will also explore the pharmacokinetics and metabolites associated with SATIVEX (R) administration to develop a protocol for differentiating between SATIVEX(R) and illicit cannabis in blood or urine among those entering cannabis withdrawal treatment. This pharmacokinetic assay will prove useful for future large scale outpatient trials should the current trial prove successful. A final exploratory objective of the study is to determine whether there is evidence of an interaction with the efficacy of SATIVEX(R) and patient characteristics on admission (including demographics and cannabis and other use and psychosocial factors such as treatment expectancy) on reported severity of cannabis withdrawal and subsequent post-withdrawal outcomes (cannabis use, psychosocial outcomes, sleep disturbances and cannabis-related problems) to be fully tested in a larger community study.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32480 0
Address 32480 0
Country 32480 0
Phone 32480 0
Fax 32480 0
Email 32480 0
Contact person for public queries
Name 15727 0
Professor Jan Copeland
Address 15727 0
National Cannabis Prevention and Information Centre, NDARC, UNSW, Sydney NSW, 2052, Australia
Country 15727 0
Australia
Phone 15727 0
+61 2 9385 0208
Fax 15727 0
+61 2 9385 0201
Email 15727 0
j.copeland@unsw.edu.au
Contact person for scientific queries
Name 6655 0
Professor Jan Copeland
Address 6655 0
National Cannabis Prevention and Information Centre, NDARC, UNSW, Sydney NSW, 2052, Australia
Country 6655 0
Australia
Phone 6655 0
+61 2 9385 0208
Fax 6655 0
+61 2 9385 0201
Email 6655 0
j.copeland@unsw.edu.au