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Trial registered on ANZCTR


Registration number
ACTRN12617001478303
Ethics application status
Approved
Date submitted
4/10/2017
Date registered
19/10/2017
Date last updated
14/02/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
N-acetylcysteine for cessation of tobacco smoking
Scientific title
A randomised, placebo controlled trial of N-acetylcysteine for cessation of tobacco smoking and 6-month post treatment abstinence in current smokers who are contemplating quitting
Secondary ID [1] 292892 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Tobacco Use Disorder 304738 0
Condition category
Condition code
Mental Health 304180 304180 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This will be a double-blind, randomised, placebo-controlled trial, to compare 900mg twice a day of N-acetylcysteine (NAC) or placebo for smoking cessation, with treatment taken daily over a period of 16 weeks. The NAC will be administered as a drink, where a 900mg effervescent tablet is dissolved in a glass of cold water and consumed. A 6-month post treatment discontinuation (week 42) follow-up will assess ongoing abstinence. Both treatment arms will receive online support using the QuitCoach (http://www.quitcoach.org.au/). QuitCoach is an online personalised quitting plan. Participants will receive login details for QuitCoach at the baseline visit and will be asked to use the website. They will be assisted if they have difficulties accessing the website, but will not be provided with additional material off-line.
Intervention code [1] 299129 0
Treatment: Drugs
Intervention code [2] 299130 0
Treatment: Other
Comparator / control treatment
Placebo + online support
The placebo is an effervescent tablet, matched to look and dissolve in water identical to the 900mg NAC effervescent tablet, but not containing any NAC or other active ingredient.
Control group
Placebo

Outcomes
Primary outcome [1] 303391 0
The primary outcome measure will be 26 weeks of continuous abstinence from tobacco smoking after the end of treatment (EoT), confirmed by biological measures. The biological measures include exhaled carbon monoxide and metabolites of nicotine measured from saliva specimens.
Timepoint [1] 303391 0
The primary timepoint will be study week 42. This point is 26 weeks after the end of treatment (EoT).
Secondary outcome [1] 338817 0
The secondary outcome measure will be abstinence from tobacco smoking after the end of treatment (EoT), confirmed by biological measures. The biological measures include exhaled carbon monoxide and metabolites of nicotine measured from saliva specimens.
Timepoint [1] 338817 0
The timepoint for the secondary outcome measure will be at week 16, the end of treatment.
Secondary outcome [2] 338818 0
Timing of the first lapse in smoking.
Timepoint [2] 338818 0
Week 16 and week 42, treatment endpoint and study endpoint.
Secondary outcome [3] 339538 0
Minnesota Nicotine Withdrawal Scale (MNWS)
Timepoint [3] 339538 0
Week 16 and week 42, treatment endpoint and study endpoint.
Secondary outcome [4] 339539 0
Questionnaire on Smoking Urges (QSU-brief)
Timepoint [4] 339539 0
Week 16 and week 42, treatment endpoint and study endpoint.
Secondary outcome [5] 339540 0
The WHO-Five Well-being Index (WHO-5)
Timepoint [5] 339540 0
Week 16 and week 42, treatment endpoint and study endpoint.
Secondary outcome [6] 339541 0
Kessler Psychological Distress Scale (K10)
Timepoint [6] 339541 0
Week 16 and week 42, treatment endpoint and study endpoint.
Secondary outcome [7] 339589 0
Between group quantitative cigarette consumption from participant self-report.
Timepoint [7] 339589 0
Weeks 8, 16 and 42.
Secondary outcome [8] 339667 0
Safety and tolerability outcomes will be assessed by comparison of reported adverse event for all NAC and placebo treated participants and for subgroups.
Timepoint [8] 339667 0
Week 16.
Secondary outcome [9] 339882 0
Timing of the first relapse, defined as self-reported smoking 7 days in a row at any time between 2 weeks post quit and the trial end.
Timepoint [9] 339882 0
Week 16 and week 42.
Secondary outcome [10] 339883 0
Prolonged abstinence defined to include any slips or lapses following the quit date, until relapse.
Timepoint [10] 339883 0
Week 16 and week 42.

Eligibility
Key inclusion criteria
Participants will be required to meet the following criteria: planning quitting smoking; aged 18 or over; capacity to consent to the study and to follow its instructions and procedures; current daily smoker of greater than or equal to 10 cigarettes per day.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants will be ineligible to enter the trial under the following conditions: Known or suspected clinically unstable systemic medical or psychiatric disorders that require acute medical treatment; current use of oral glucocorticoids; active gastrointestinal ulcers; pregnancy or breastfeeding, or planning a pregnancy within 6 months; current use of greater than 500mg NAC/day; a history of anaphylactic reaction to NAC or any component of the preparation. Only one member of a household will be permitted to participate in the trial concurrently to minimise cohort-confounding effects.

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)
The randomisation code has been generated by a researcher who has no other involvement in this study. The code has been sent to the pharmacist and another copy has been retained on a password protected computer. Every allocation is coded by a two digit number.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Web based software was used to generate the randomisation code. Block randomisation with varying block sizes has been implemented.
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
Parallel
Other design features
The primary outcome of this aid-to-cessation trial will be between group differences in continuous abstinence for the 26-week period between weeks 16 and 42. The primary outcome is measured at 6 months post-treatment discontinuation (week 42) rather than at treatment discontinuation (week 16).
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
We will adhere to 'intention-to-treat' principles following CONSORT Statement guidelines. Baseline data will be secured prior to treatment allocation, missing values will be scrutinized to check for non-random distribution and analyses that utilize baseline data will be executed twice: once using observed data, and once using multiple. The proportions of relapse between the treatment groups (control vs intervention) will compared and odds ratio and 95% confidence interval will be reported.

For secondary outcomes 2 and 9 (time to first lapse; and time to first relapse) log-rank test will be used to compare survival distributions between intervention and placebo groups, and hazard ratio with 95% confidence interval using proportional Cox regression will be reported as the effect size.
Secondary outcome 10 will be analysed using the same techniques as the main outcome.

Subgroup analyses will be performed for groups categorised by demographic and diagnostic variables including gender, age, SCID diagnosis and Adult ADHD Self-Report Scale. These variables are not outcomes, they are descriptors of the cohort.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 9031 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment postcode(s) [1] 17511 0
3220 - Geelong
Recruitment postcode(s) [2] 17602 0
3000 - Melbourne

Funding & Sponsors
Funding source category [1] 297524 0
Charities/Societies/Foundations
Name [1] 297524 0
The ARC Harry Windsor Research Grants Scheme
Address [1] 297524 0
Australian Respiratory Council
Level 6,
431 Glebe Point Road
Sydney NSW 2037
Australia

PO Box 942
Broadway NSW 2007
Country [1] 297524 0
Australia
Primary sponsor type
Hospital
Name
Barwon Health
Address
University Hospital Geelong
Bellerine Street (main entrance)
Ryrie Street (emergency entrance)

P.O. Box 281
Geelong VIC 3220
Country
Australia
Secondary sponsor category [1] 296612 0
None
Name [1] 296612 0
Address [1] 296612 0
Country [1] 296612 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298620 0
Barwon Health Human Research Ethics Committee
Ethics committee address [1] 298620 0
PO Box 281

Geelong VIC 3220
Ethics committee country [1] 298620 0
Australia
Date submitted for ethics approval [1] 298620 0
03/03/2017
Approval date [1] 298620 0
19/06/2017
Ethics approval number [1] 298620 0
17/15
Ethics committee name [2] 298691 0
Deakin University Human Research Ethics Committee
Ethics committee address [2] 298691 0
Ethics committee country [2] 298691 0
Australia
Date submitted for ethics approval [2] 298691 0
23/06/2017
Approval date [2] 298691 0
24/07/2017
Ethics approval number [2] 298691 0
2017-193

Summary
Brief summary
The aim of this project is to investigate the efficacy of N-acetylcysteine (NAC) (1.8g/day) for smoking cessation in a randomised, placebo-controlled trial of current smokers who wish to quit smoking. The primary outcome measure will be 6 months of continuous abstinence from end of treatment (EoT) in tobacco smoking, confirmed by biological measures. Secondary outcome measures include point prevalence abstinence, time to relapse and cigarette consumption. Safety, tolerability and subgroup analyses will also be conducted.

Hypotheses:
Primary: Treatment with NAC will be superior to placebo for smoking cessation at follow-up (week 42), confirmed by assaying exhaled carbon monoxide and salivary cotinine.
Secondary: Treatment with NAC will be superior to placebo for smoking cessation at treatment endpoint (week 16), confirmed by assaying exhaled carbon monoxide and salivary cotinine.

NAC is an agent that replenishes the antioxidant glutathione, and also has intrinsic antioxidant actions, as well as modulating glutamatergic, neurotropic and inflammatory pathways.There is evidence that glutamate and in particular the cystine-glutamate exchange system, mediate drug intake, craving and behavioural sensitisation in preclinical models of addiction. Glutamate, which is increased by NAC via cysteine-glutamate exchange, is core to relapse in addiction. NAC can also improve some of the physical harms caused by tobacco smoke exposure, improving mucociliary transport and preventing oxidative damage to lung and other tissues.
NAC has several advantages over other pharmacotherapies: a different mechanism of action for smoking cessation, an excellent tolerability profile, low cost and is readily available.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 2083 2083 0 0
Attachments [2] 2084 2084 0 0

Contacts
Principal investigator
Name 77674 0
A/Prof Seetal Dodd
Address 77674 0
University Hospital Geelong
Health Education and Research Building (HERB), Rm. 3.22,
285 Ryrie Street,
Geelong, Victoria, 3220
Country 77674 0
Australia
Phone 77674 0
+61 3 42153299
Fax 77674 0
Email 77674 0
seetald@barwonhealth.org.au
Contact person for public queries
Name 77675 0
Ms Lauren Arancini
Address 77675 0
University Hospital Geelong
Health Education and Research Building (HERB), Rm. 3.22,
285 Ryrie Street,
Geelong, Victoria, 3220
Country 77675 0
Australia
Phone 77675 0
+61 481 911 601
Fax 77675 0
Email 77675 0
LAUREN.ARANCINI@barwonhealth.org.au
Contact person for scientific queries
Name 77676 0
A/Prof Seetal Dodd
Address 77676 0
University Hospital Geelong
Health Education and Research Building (HERB), Rm. 3.22,
285 Ryrie Street,
Geelong, Victoria, 3220
Country 77676 0
Australia
Phone 77676 0
+61 3 42153299
Fax 77676 0
Email 77676 0
seetald@barwonhealth.org.au

No information has been provided regarding IPD availability
Summary results
No Results