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Trial registered on ANZCTR


Registration number
ACTRN12616000847415
Ethics application status
Approved
Date submitted
23/06/2016
Date registered
29/06/2016
Date last updated
16/11/2018
Date data sharing statement initially provided
16/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
N-acetyl cysteine (NAC) augmentation in Obsessive-Compulsive Disorder (OCD): A 24-week, randomized, double blind placebo controlled trial
Scientific title
N-acetyl cysteine (NAC) augmentation in Obsessive-Compulsive Disorder (OCD): A 24-week, randomized, double blind placebo controlled trial
Secondary ID [1] 289527 0
None
Universal Trial Number (UTN)
Trial acronym
NAC-OCD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obsessive-Compulsive Disorder 299233 0
Condition category
Condition code
Mental Health 299243 299243 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The amino acid N-acetyl cysteine (NAC; 500mg per capsule, taken orally) or placebo (capsules containing microcellulose), used adjunctive to stable medication (minimum 8-weeks at consistent dosages) for 24 weeks in adults (18-75 years of age) with OCD.

Randomised participants will take 2 capsules, twice per day (equating to 2,000mg NAC or placebo per day) for the first 8-weeks of the study. However, the dose of NAC (or placebo) may increase from the week-8 visit. In cases of non-response (<35% reduction in baseline score of primary outcome measure: Y-BOCS), participants will increase their dose by an additional 1,000mg per day (3 capsules taken orally twice per day; equating to 3,000mg NAC or placebo per day) from week-8 and remain on this dose for the following 4-weeks. If the participant continues to be non-responsive at the week-12 visit, an additional 1,000mg may be added (4 capsules taken orally twice per day).

The maximum dose permitted in this study will be 4,000mg per day, however, participants will only be permitted to increase their dose by 1,000mg (per day) at a time and must remain on this dose for a minimum of 4-weeks before further titration can occur. Titration may occur at week-8, week-12, week-16 and week-20 in cases of non response. If the participant has reported any side effects/adverse events, titration will only occur if deemed suitable by the medical investigators.

Participants will be asked to return all remaining capsules in their containers at each study follow-up visit. Remaining capsules will be counted by a 3rd party to determine participant compliance.
Intervention code [1] 295119 0
Treatment: Drugs
Comparator / control treatment
Placebo capsules containing microcellulose
Control group
Placebo

Outcomes
Primary outcome [1] 298725 0
Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), clinician administrated (severity scale Q1-Q10 and insight Q11)
Timepoint [1] 298725 0
Baseline, Week-4, Week-8, Week-12, Week-16, Week-20, Week-24
Secondary outcome [1] 325064 0
Structured Interview Guide for the Hamilton Depression Rating Scale (HAM-D; 17-item), clinician administrated
Timepoint [1] 325064 0
Baseline, Week-4, Week-8, Week-12, Week-16, Week-20, Week-24
Secondary outcome [2] 325068 0
Beck Anxiety Inventory (BAI), self-reported
Timepoint [2] 325068 0
Baseline, Week-4, Week-8, Week-12, Week-16, Week-20, Week-24
Secondary outcome [3] 325069 0
Sheehan Disability Scale (SDS), self-reported
Timepoint [3] 325069 0
Baseline, Week-4, Week-8, Week-12, Week-16, Week-20, Week-24
Secondary outcome [4] 325070 0
World Health Organisation Quality of Life Brief (WHOQOL-bref), self-reported
Timepoint [4] 325070 0
Baseline, Week-12, Week-20
Secondary outcome [5] 325071 0
Clinical Global Impression Scale (CGI), clinician administrated
Timepoint [5] 325071 0
Baseline, Week-4, Week-8, Week-12, Week-16, Week-20, Week-24
Secondary outcome [6] 325072 0
Participant Global Impression scale (PGI), self-reported
Timepoint [6] 325072 0
Baseline, Week-4, Week-8, Week-12, Week-16, Week-20, Week-24
Secondary outcome [7] 325074 0
Barratt Impulsivity Scale
Timepoint [7] 325074 0
Baseline only, used as a predictor of response/non-response
Secondary outcome [8] 325076 0
Dietary Questionnaire for Epidemiological Studies version 3.2
Timepoint [8] 325076 0
Baseline only
Secondary outcome [9] 325077 0
Systematic Assessment for Treatment Emergent Events (SAFTEE), self reported.

NAC may induce gastrointestinal side effects including mild abdominal pain or discomfort, heartburn, diarrhea, flatulence, nausea and cramps. Headaches and skin rashes have also been reported in previous clinical studies. However, specific to psychiatric research studies, only a small minority of participants have withdrawn due to side effects of NAC including a skin rash (n = 1), aggression (n = 1), severe heartburn (n = 1), neutropenia with 6 grams of NAC which resolved when dose reduced to 2.4g, (n = 1) and sensorineural deafness (n = 1) (Slattery et al., 2015).
Timepoint [9] 325077 0
Week-4, Week-8, Week-12, Week-16, Week-20, Week-24
Secondary outcome [10] 347744 0
Dimensional Obsessive Compulsive Scale (DOCS) - self-reporting
Timepoint [10] 347744 0
Baseline, Week-4, Week-8, Week-12, Week-16, Week-20, Week-24

Eligibility
Key inclusion criteria
Primary diagnosis of OCD as per the Structured Interview Guide for the DSM-5 (SCID)
Adults between the age of 18-75 who have the desire and capacity to consent to the study and follow its procedures.

Minimum score of 16 on the Y-BOCS at time of entry into the study, but no greater than 31.

Currently taking medication for their OCD which has been at a stable dose for the past 8-weeks.

Stable psychological treatment (if employing) for minimum eight weeks (an 8-week wash-out period will be required if participants have just completed an intensive in-patient CBT program for their OCD).
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
*Bipolar disorder
*Psychotic disorders
*Primary diagnosis of Obsessive-compulsive spectrum disorders including hoarding, body dysmorphic disorder, trichotillomania (secondary diagnosis permitted)
*Severe depression (as defined by HAM-D score equal to or greater than 24
*Alcohol/substance abuse
*Y-BOCS score equal to or greater than 32
*Treatment resistant OCD (3 or more trials of first line medications for their OCD at therapeutic doses for minimum of 12-weeks each, at least one augmentation strategy, for example, anti psychotic medication as well as exposure response prevention therapy minimum 20 hours)
*Medications with known or suspected negative interactions with NAC (activated charcoal, nitro glycerine, insulin replacement therapies, Aralen, anti-coagulant medications excluding aspirin and NSAIDS)

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation of participants to treatment groups will be determined by computerised random allocation. Recruited eligible participants will be assigned a participant number and provided capsules according to a corresponding investigational product (IP) number. Participant numbers are provided sequentially and the randomisation code is set up in a 2 by 2 block design, with no group identifying them (to avoid potentially unblinding researcher’s if participants were randomised to medication bottles labelled A or B).
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
Participants will be randomised into either NAC or placebo in a double blind manner.
Phase
Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
A sample size of 200 participants (100 participants in each arm) are to be recruited and intention-to-treat principles will be applied to all data. A large sample of 200 participants is powered to detect a potential small to moderate effect size (f = 0.15) difference between NAC and placebo beyond treatment as usual, approximating a clinically significant 3 point reduction on the Y-BOCS (using all post-baseline data via intention-to-treat analysis). Based on an ANOVA model over seven time-points, a two tailed analysis with alpha = 0.05, beta = 0.80, and a critical F of 3.78; 200 participants (not including drop-outs) are required to detect a small to moderate effect size difference in Y-BOCS scale score between treatment and placebo.

The primary efficacy analysis will assess mean treatment group differences for the primary outcome measure (Y-BOCS) using a mixed-effects model, repeated measures approach (MMRM). Results from the analysis of dichotomous data (e.g. demographics data) will be presented as proportions with 95% confidence interval, and Fisher’s Exact p-value where appropriate. Analysis of covariance (ANCOVA) will also be used to compare differences between treatment means in changes from baseline to week 20 last observation carried forward (LOCF) endpoint. The ANCOVA model will assess confounding covariates including intervention type (medication or psychological care), as well as age, gender, weight, physical activity levels, smoking and alcohol consumption.

Non-parametric statistics will be used when assumptions for parametric methods are violated. Effect sizes will be calculated using Cohen’s d. All tests of treatment effects will be conducted using a two-tailed alpha level of 0.05 and 95% confidence intervals. Data will be analysed via SPSS 23.0.

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)
NSW,QLD,VIC
Recruitment hospital [1] 6014 0
The Melbourne Clinic - Richmond
Recruitment hospital [2] 6015 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 13441 0
3121 - Richmond
Recruitment postcode(s) [2] 13442 0
4001 - Brisbane
Recruitment postcode(s) [3] 24712 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 293903 0
Government body
Name [1] 293903 0
The National Heath and Medical Research Council
Address [1] 293903 0
Level 1
16 Marcus Clarke Street
Canberra ACT 2601
Country [1] 293903 0
Australia
Primary sponsor type
University
Name
The University of Melbourne
Address
Parkville,
Melbourne VIC
Australia, 3052
Country
Australia
Secondary sponsor category [1] 292728 0
University
Name [1] 292728 0
The University of Queensland
Address [1] 292728 0
St Lucia
QLD 4072
Country [1] 292728 0
Australia
Secondary sponsor category [2] 295732 0
University
Name [2] 295732 0
Western Sydney University
Address [2] 295732 0
Western Sydney University
Westmead Campus
158-160 Hawkesbury Rd
Westmead, NSW, 2145
Country [2] 295732 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295320 0
The Melbourne Clinic Research Ethics Committee
Ethics committee address [1] 295320 0
2 Salisbury St,
Richmond
Melbourne
VIC 3121
Ethics committee country [1] 295320 0
Australia
Date submitted for ethics approval [1] 295320 0
25/05/2016
Approval date [1] 295320 0
08/06/2016
Ethics approval number [1] 295320 0
279
Ethics committee name [2] 297979 0
Western Sydney University Human Research Ethics Committee
Ethics committee address [2] 297979 0
Penrith Campus
Great Western Highway
Werrington
NSW 2747
Ethics committee country [2] 297979 0
Australia
Date submitted for ethics approval [2] 297979 0
30/03/2017
Approval date [2] 297979 0
13/04/2017
Ethics approval number [2] 297979 0
H12181
Ethics committee name [3] 297980 0
UQ Medical Research Ethics Committee (MREC)
Ethics committee address [3] 297980 0
University of Queensland (UQ)
Level 3, Brian Wilson Chancellery
The University of Queensland
St Lucia QLD 4072, Australia
Ethics committee country [3] 297980 0
Australia
Date submitted for ethics approval [3] 297980 0
11/10/2016
Approval date [3] 297980 0
08/12/2016
Ethics approval number [3] 297980 0
2016001720

Summary
Brief summary
This study seeks to elucidate the benefits of NAC augmentation (2-4 grams/day) compared to placebo in the treatment of OCD, in a 24-week, multi-centre, randomized, double-blind, placebo controlled trial. It is hypothesized that NAC will be superior over placebo for improving OCD symptoms as measured by a reduction in Y-BOCS scores from baseline against each subsequent time point (W4, W8, W12, W16, W20 and W24). Additional benefits are anticipated for relieving anxiety as well as improving mood, functioning and overall quality of life.
Trial website
ocd-research.com
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 66874 0
Prof Jerome Sarris
Address 66874 0
The Melbourne Clinic Professorial Unit
2 Salisbury St,
Richmond
Melbourne VIC 3121
Country 66874 0
Australia
Phone 66874 0
+61 3 94874748
Fax 66874 0
Email 66874 0
jsarris@unimelb.edu.au
Contact person for public queries
Name 66875 0
Miss Georgina Oliver
Address 66875 0
The Melbourne Clinic Professorial Unit
2 Salisbury St,
Richmond
Melbourne VIC 3121
Country 66875 0
Australia
Phone 66875 0
+61 3 94874659
Fax 66875 0
Email 66875 0
georgina.oliver@unimelb.edu.au
Contact person for scientific queries
Name 66876 0
Miss Georgina Oliver
Address 66876 0
The Melbourne Clinic Professorial Unit
2 Salisbury St,
Richmond
Melbourne VIC 3121
Country 66876 0
Australia
Phone 66876 0
+61 3 94874659
Fax 66876 0
Email 66876 0
georgina.oliver@unimelb.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Participants have not consented to provide IPD
What supporting documents are/will be available?
Clinical study report
How or where can supporting documents be obtained?
Type [1] 256 0
Clinical study report
Citation [1] 256 0
Link [1] 256 0
Email [1] 256 0
Other [1] 256 0
A clinical study report will be provided when the study has been completed.
Attachment [1] 256 0
Summary results
No Results