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Trial registered on ANZCTR


Registration number
ACTRN12617001626358
Ethics application status
Approved
Date submitted
1/11/2017
Date registered
13/12/2017
Date last updated
27/05/2019
Date data sharing statement initially provided
30/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A Randomized Controlled Trial of Oxytocin Nasal Spray for Alcohol Dependence
Scientific title
A Randomized Controlled Trial to evaluate the effect of Oxytocin Nasal Spray on number of heavy drinking days and craving in adults with Alcohol Dependence.
Secondary ID [1] 293254 0
Nil
Universal Trial Number (UTN)
Trial acronym
ONSAD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
alcohol dependence 305303 0
Condition category
Condition code
Mental Health 304608 304608 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study involves assessing the effect of oxytocin nasal spray (20 international units sprayed into each nostril, twice a day for 12 weeks) for alcohol dependence through a double blinded randomised placebo controlled trial. Participants will be randomised to receive either an active oxytocin nasal spray or inactive placebo nasal spray.
Participants will be a given a drug diary to track adherence and potential side effects, and drug bottles will be weight before and after treatment by the study coordinator. Oxytocin levels will be measured in the blood at pre and post treatment. To ensure adequate follow-up data, participants will be reimbursed for their time for 1 month and 6 month follow up, with a $50 gift voucher.
Intervention code [1] 299516 0
Treatment: Drugs
Comparator / control treatment
There will be a blinded placebo group who receive a placebo nasal spray for 12 weeks
Control group
Placebo

Outcomes
Primary outcome [1] 303837 0
Proportion of participants with a reduction in number of heavy drinking days at 12 weeks post commencement of treatment, 16 weeks post commencement of treatment and 6 months post commencement of treatment. A heavy drinking day is defined as a day when 4 or more drinks are consumed. This will be assessed using the drug diary and the timeline followback method.
Timepoint [1] 303837 0
6 weeks post commencement of treatment with a primary time point of 12 weeks post commencement of treatment and follow-up time points at 16 weeks post commencement of treatment and 6 months post commencement of treatment.
Secondary outcome [1] 340256 0
Proportion of participants with a reduction in craving assessed using the Obsessive Compulsive Drinking Scale (OCDS) at 6weeks post commencement of treatment, 12 weeks post commencement of treatment, 16 weeks post commencement of treatment and 6 months post commencement of treatment
Timepoint [1] 340256 0
6 weeks post commencement of treatment, 12 weeks post commencement of treatment, 16 weeks post commencement of treatment and 6 months post commencement of treatment
Secondary outcome [2] 340589 0
Number of participants with improved composite scores in executive function tests including learning and memory using the Cambridge Neuropsychological Test Automated Battery, Rey auditory verbal learning test and Trail Making Test.
Timepoint [2] 340589 0
Pre-treatment, 12 weeks post commencement of treatment and 6 months post commencement of treatment. This change was made prior to any enrolments.
Secondary outcome [3] 340590 0
Changes in blood oxygen-level dependent (BOLD) between participants during an alcohol cue reactivity task as measured by functional magnetic resonance imaging (fMRI).
Timepoint [3] 340590 0
fMRI has 2 time points; pre-treatment and 12-weeks post-treatment.
Secondary outcome [4] 341100 0
Proportion of participants which show a change in amount of metabolite N-acetyl-aspartate using magnetic resonance imaging (MRI)
Timepoint [4] 341100 0
MRI has two time points; pre-treatment and 12 weeks post-treatment.

Eligibility
Key inclusion criteria
• Aged between 18 and 65 years of age
• Meet the International Classification of Diseases, 10th Revision (ICD10), criteria for alcohol dependence
• Fluency in English
• Ability to give informed consent
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Women lactating, pregnant or childbearing potential who are not willing to avoid pregnancy during the study
• Meet criteria for severe acute psychiatric disorders including psychosis or moderate/high risk for self-harm (suicidality)
• Meet International Statistical Classification of Diseases and Related Health Problems (ICD-10) criteria for another substance dependence (other than nicotine, due to high comorbidity between these disorders
• Currently participating in another substance use treatment
• People with pending legal charges and potential incarceration
• IQ below 75 (assessed using the Weschler Test of Adult Reading (WTAR)
• Those who have severely compromised cardiac, hepatic or renal function (evidenced at medical examination)
• Use of benzodiazepines

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)
Trial randomisation codes will be generated by the dispensing pharmacist at Royal Prince Alfred Hospital Pharmacy, who will hold a copy of the codes and their association with either OT or placebo nasal sprays. Once a treatment pack has been allocated to a participant, its corresponding code will be recorded in the participants’ electronic and hardcopy file, as well as recorded on the drug accountability log sheets at the pharmacy of each site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
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
Phase
Phase 2 / Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size calculations are based upon the effect size demonstrated on these key outcomes in our previous trials 6 such that, based on a two-sided significance level of 0.05, at least 80% power and assuming 1:1 randomisation, a total of 80 participants (40 in each arm) are needed to detect an effect size of 0.50 (medium-large) between groups. An intention-to-treat approach will be used to handle dropout from the trial. In our most recent NHMRC-funded trial of alcohol pharmacotherapy we obtained a treatment retention rate of 70%. Of the remaining 30% who were either non-compliant, or dropped out (relapse, hospitalization, unwillingness etc), we obtained drinking data from all but 5 subjects. Allowing for a 30% refusal rate from our previous trials, we estimate screening approximately 130 potential participants. Our sample size is sufficient based on this data to show effects of a similar magnitude. We previously showed that while baseline levels were similar between groups, OT reduced heavy drinking days to a mean of 13.34 (CI 9.68 - 17.00) at one month follow-up, while in the placebo 18.86 (CI–14.57-23.15) days, SD = 6.17. Using these data, we would be able to show an effect below p< 0.012 with 86 participants. We recruit 100 to account for this and some of our secondary measures (e.g., depression) in our pilot trial showed more moderate effect sizes from oxytocin (d= 0.50). We believe the sample size provides the right balance between feasibility and power for a phase 2 trial. We screen 130 patients to achieve 100 drug assigned participants. The choice of this sample size for neuroimaging is based on previous study employing MRS assessing outcome in alcohol dependence. Measures show moderate effect sizes between alcohol patients and controls (e.g., Cohens D= 0.79) and from pre-treatment to post (e.g., Cohen’s D = 0.66). Analysis employing ANOVA: 2 (baseline vs post OT) x 3 (brain region: anterior cingulate cortex vs thalamus vs hippocampus) x 5 (metabolites: NAA vs myoinositol vs glutamate vs glutathione vs creatine).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
28/02/2019
Actual
Date of last participant enrolment
Anticipated
26/02/2021
Actual
Date of last data collection
Anticipated
26/08/2021
Actual
Sample size
Target
100
Accrual to date
0
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 9315 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 17982 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 297807 0
Government body
Name [1] 297807 0
National Health and Medical Research Council
Country [1] 297807 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
94 Mallett Street
Camperdown NSW 2050
Country
Australia
Secondary sponsor category [1] 296935 0
None
Name [1] 296935 0
Address [1] 296935 0
Country [1] 296935 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298865 0
Royal Prince Alfred Human Research Ethics Committee
Ethics committee address [1] 298865 0
Royal Prince Alfred Hospital
Camperdown NSW 2050
Ethics committee country [1] 298865 0
Australia
Date submitted for ethics approval [1] 298865 0
10/04/2017
Approval date [1] 298865 0
05/07/2017
Ethics approval number [1] 298865 0
X17-0110 HREC/17/RPAH/160

Summary
Brief summary
The project is a double blind, between subject, randomised controlled study. Specifically the study will assess the impact of OT on the number of heavy drinking days and alcohol craving. The study will also investigate the potential neuroprotective benefits of OT, by assessing learning and memory, executive functions and changes in neurometabolites measured through neuropsychological assessments and MRI. Participants will be recruited through the drug and alcohol centre at Royal Prince Alfred Hospital, as well as community recruitment through media and Facebook. They will be required to attend a screening and eligibility assessment and if eligible be randomised to receive placebo or OT nasal spray, which will need to be self-administered twice a day, for 12 weeks. Participants will be asked to return at 6 weeks (mid-treatment), 12 weeks (end of treatment), 1 month post follow-up, and 6 months post end of treatment for further follow-up. During the study, participants will be asked to complete a number of self-report questionnaires, undergo physiological, neuropsychological and neuroimaging assessments, as well as provide urine and blood sample.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 78482 0
Prof Adam Guastella
Address 78482 0
Brain and Mind Centre
University of Sydney
94 Mallett Street
Camperdown NSW 2050
Country 78482 0
Australia
Phone 78482 0
+61 2 9351 0539
Fax 78482 0
Email 78482 0
[email protected]
Contact person for public queries
Name 78483 0
Nicollette Thornton
Address 78483 0
Brain and Mind Centre
University of Sydney
94 Mallett Street
Camperdown NSW 2050
Country 78483 0
Australia
Phone 78483 0
+61 2 9351 0742
Fax 78483 0
Email 78483 0
[email protected]
Contact person for scientific queries
Name 78484 0
Nicollette Thornton
Address 78484 0
Brain and Mind Centre
University of Sydney
94 Mallett Street
Camperdown NSW 2050
Country 78484 0
Australia
Phone 78484 0
+61 2 9351 0742
Fax 78484 0
Email 78484 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Data will be published in relevant peer reviewed journal. Due to privacy and confidentiality laws, individual patient data will not be shared.


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.