ANZCTR - Registration

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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]

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

Cannabis use disorder

Condition category

Condition code

Mental Health

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]

Treatment: Drugs

Comparator / control treatment

Placebo nasal spray containing 0.9% Sodium Chloride saline.

Control group

Placebo

Outcomes

Primary outcome [1]

Occasions of cannabis or cigarette use per day, as per participant self-report

Timepoint [1]

Days 1, 2 and 3 of active treatment compared to days 1, 2 and 3 of placebo treatment.

Secondary outcome [1]

Anxiety, as assessed by STAI scores (Spielberger, 1985).

Timepoint [1]

Days 1, 2 and 3 of active treatment compared to days 1, 2 and 3 of placebo treatment.

Secondary outcome [2]

Withdrawal symptoms as assessed by the Mood and Physical Symptoms Scale (cigarette arm) or the Cannabis Withdrawal Scale (cannabis arm)

Timepoint [2]

Days 1, 2 and 3 of active treatment compared to days 1, 2 and 3 of placebo treatment.

Secondary outcome [3]

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]

Days 1, 2 and 3 of active treatment compared to days 1, 2 and 3 of placebo treatment.

Secondary outcome [4]

Adverse events as reported by participants and/or investigators

Timepoint [4]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Recruitment postcode(s) [1]

6008 - Subiaco

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Go Medical Industries Pty Ltd

Address [1]

200 Churchill Ave, Subiaco WA 6008

Country [1]

Australia

Funding source category [2]

University

Name [2]

The University of Western Australia

Address [2]

35 Stirling Hwy, Crawley WA 6009

Country [2]

Australia

Funding source category [3]

Other

Name [3]

Fresh Start Recovery Programme

Address [3]

65 Townshend Rd, Subiaco WA 6008

Country [3]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Southcity Medical Centre Human Research Ethics Committe

Ethics committee address [1]

39 Gladstone Road, Highgate Hill QLD 4104

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

19/06/2015

Approval date [1]

24/12/2015

Ethics approval number [1]

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

A/Prof George O'Neil

Address

Fresh Start Recovery Programme
65 Townshend Rd, Subiaco WA 6008

Country

Australia

Phone

+61 8 9381 1333

Fax

email@drgeorgeoneil.com

Contact person for public queries

Name

George O'Neil

Address

Fresh Start Recovery Programme
65 Townshend Rd, Subiaco WA 6008

Country

Australia

Phone

+61 8 9381 1333

Fax

email@drgeorgeoneil.com

Contact person for scientific queries

Name

George O'Neil

Address

Fresh Start Recovery Programme
65 Townshend Rd, Subiaco WA 6008

Country

Australia

Phone

+61 8 9381 1333

Fax

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

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

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