Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617000325303
Ethics application status
Approved
Date submitted
24/01/2017
Date registered
1/03/2017
Date last updated
5/02/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Nasal naloxone and flumazenil effects on cigarette and cannabis craving and abstinence
Scientific title
A pilot study to evaluate nasal naloxone and flumazenil effects on cigarette and cannabis craving and abstinence in those with tobacco use disorder or cannabis use disorder
Secondary ID [1] 290889 0
Nil known
Universal Trial Number (UTN)
U1111-1188-3780
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Tobacco use disorder 301603 0
Cannabis use disorder 302283 0
Condition category
Condition code
Mental Health 301310 301310 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A double-blind, placebo-controlled, cross-over, randomized clinical trial of a flumazenil and naloxone nasal spray, delivering 200 mcg flumazenil and 200 mcg naloxone per dose, for the treatment of cravings and anxiety associated with cessation of cigarette or cannabis smoking. Participants are required to attempt 2 separate 3 day smoke free periods, 1 week apart, using a different nasal spray each time throughout each with a 4-day 'washout' period in between. If week 1 is active then week 2 will be placebo and vice versa. The spray is to be administered 'as required' for relief of craving and anxiety, up to half-hourly and the daily dose will be recorded based on participants self-reported frequency of use.
Intervention code [1] 296949 0
Treatment: Drugs
Comparator / control treatment
Placebo nasal spray containing 0.9% Sodium Chloride saline.
Control group
Placebo

Outcomes
Primary outcome [1] 300853 0
Occasions of cannabis or cigarette use per day, as per participant self-report
Timepoint [1] 300853 0
Days 1, 2 and 3 of active treatment compared to days 1, 2 and 3 of placebo treatment.
Secondary outcome [1] 331036 0
Anxiety, as assessed by STAI scores (Spielberger, 1985).
Timepoint [1] 331036 0
Days 1, 2 and 3 of active treatment compared to days 1, 2 and 3 of placebo treatment.
Secondary outcome [2] 331054 0
Withdrawal symptoms as assessed by the Mood and Physical Symptoms Scale (cigarette arm) or the Cannabis Withdrawal Scale (cannabis arm)
Timepoint [2] 331054 0
Days 1, 2 and 3 of active treatment compared to days 1, 2 and 3 of placebo treatment.
Secondary outcome [3] 332261 0
Craving as assessed by 2 items of the Mood and Physical Symptoms Scale (cigarette arm) or a single item of the Cannabis Withdrawal Scale (cannabis arm)
Timepoint [3] 332261 0
Days 1, 2 and 3 of active treatment compared to days 1, 2 and 3 of placebo treatment.
Secondary outcome [4] 332262 0
Adverse events as reported by participants and/or investigators
Timepoint [4] 332262 0
Upon conclusion of both cigarette-free periods and use of both nasal sprays

Eligibility
Key inclusion criteria
Daily cigarette smokers who meet DSM-V criteria for tobacco use disorder or daily cannabis smokers who meet DSM-V criteria for cannabis use disorder
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants will be excluded if they suffer epilepsy or have a history of seizures or fitting, are pregnant or are breastfeeding, are dependent on benzodiazepines or opiates, are under 18 years of age or are unable and unwilling to provide informed consent.

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 will be concealed by using identical packaging for placebo and active treatments which are pre-labelled with participant ID's by an appointed person who does not have any other involvement in the trial or any contact with clinic patients.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple blocked randomisation with randomly selected block sizes was used. The randomisation sequence was created using an online randomisation service,
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Data will be analysed using SPSS. Independent samples 2-tailed t-tests with bonferonni corrections will be used to compare the level of cigarette or cannabis consumption between the two treatment conditions at each time point. Independent samples 2-tailed t-tests with bonferonni corrections will also be used to compare anxiety, craving and withdrawal symptom scores between the two treatment groups at each time point. 2-way between-subjects ANOVA with Tukey post-hoc analysis will be used to compare differences across the duration of treatment.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
27/09/2016
Date of last participant enrolment
Anticipated
1/05/2018
Actual
Date of last data collection
Anticipated
17/05/2018
Actual
Sample size
Target
60
Accrual to date
45
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment postcode(s) [1] 15153 0
6008 - Subiaco

Funding & Sponsors
Funding source category [1] 295412 0
Commercial sector/Industry
Name [1] 295412 0
Go Medical Industries Pty Ltd
Country [1] 295412 0
Australia
Funding source category [2] 295413 0
University
Name [2] 295413 0
The University of Western Australia
Country [2] 295413 0
Australia
Funding source category [3] 295414 0
Other
Name [3] 295414 0
Fresh Start Recovery Programme
Country [3] 295414 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Go Medical Industries Pty Ltd
Address
200 Churchill Ave, Subiaco WA 6008
Country
Australia
Secondary sponsor category [1] 294233 0
None
Name [1] 294233 0
Address [1] 294233 0
Country [1] 294233 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296747 0
Southcity Medical Centre Human Research Ethics Committe
Ethics committee address [1] 296747 0
39 Gladstone Road, Highgate Hill QLD 4104
Ethics committee country [1] 296747 0
Australia
Date submitted for ethics approval [1] 296747 0
19/06/2015
Approval date [1] 296747 0
24/12/2015
Ethics approval number [1] 296747 0
003/2015

Summary
Brief summary
Despite cigarette smoking being the leading cause of preventable death in the western societies, around 15% of people over the age of 14 are daily cigarette smokers in Australia (Australian Institute of Health and Welfare, 2011). The high prevalence of cigarette smoking can in part be attributed to the fact that they are legal and can be readily purchased and in part to their content of nicotine, which is more addictive than both amphetamines and alcohol (Nutt et al., 2007).
For regular cigarette smokers, attempts to abstain from smoking result in an unpleasant withdrawal syndrome, symptoms of which include depressed mood, irritability, frustration, difficulty concentrating, anxiety, insomnia and increased appetite (American Psychiatric Association, 2013). Success rates for quitting smoking for at least one year without pharmacological intervention are quite low, at around 10% (Silagy et al., 2004). Of the pharmacotherapies available to aid with quitting cigarettes, varenicline is the most effective, with as abstinence rate of 30.5% at 12 months. While varenicline is more effective than other available therapies such as nicotine replacement and bupropion, the poor outcome for the majority of smokers demonstrates a clear need for a pharmacotherapy with greater efficacy.
In moderate and heavy smokers, cravings and anxiety begin to occur within 1 hour of the last cigarette smoked (Hendricks et al., 2006). Given that heavy smokers are known to have an average interval of around 40 minutes between cigarettes, this supports the idea that smokers use cigarettes to relieve these early symptoms (Hatsukami et al., 1988). Flumazenil has been reported to reduce feeling of anxiety, while naloxone has been shown to have anti-craving effects. This had led to the development of a pulsatile fast-acting delivery system for flumazenil and naloxone which may be administered at the time of craving. It is hypothesised that this pharmacotherapy will provide immediate relieve of withdrawal cravings and anxiety which are normally a precursor to on-going smoking and will therefore increase the rates of success for people attempting to quit cigarettes.
The proposed pilot study aims to assess the efficacy of combined flumazenil and naloxone in the form of a nasal spray which is to be administered at the time of craving or feelings of withdrawal symptoms to promote cigarette and cannabis smoking abstinence.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 71638 0
A/Prof George O'Neil
Address 71638 0
Fresh Start Recovery Programme
65 Townshend Rd, Subiaco WA 6008
Country 71638 0
Australia
Phone 71638 0
+61 8 9381 1333
Fax 71638 0
Email 71638 0
email@drgeorgeoneil.com
Contact person for public queries
Name 71639 0
A/Prof George O'Neil
Address 71639 0
Fresh Start Recovery Programme
65 Townshend Rd, Subiaco WA 6008
Country 71639 0
Australia
Phone 71639 0
+61 8 9381 1333
Fax 71639 0
Email 71639 0
email@drgeorgeoneil.com
Contact person for scientific queries
Name 71640 0
A/Prof George O'Neil
Address 71640 0
Fresh Start Recovery Programme
65 Townshend Rd, Subiaco WA 6008
Country 71640 0
Australia
Phone 71640 0
+61 8 9381 1333
Fax 71640 0
Email 71640 0
email@drgeorgeoneil.com

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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