Back to resultsA Randomised Controlled Trial of N-acetylcysteine for the Management of Alcohol Use Disorder (NAC-AUD)
Primary Purpose
Alcohol Use Disorder (AUD)
Status
Recruiting
Phase
Phase 4
Locations
Australia
Study Type
Interventional
Intervention
N-acetyl cysteine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Alcohol Use Disorder (AUD) focused on measuring N-acetyl Cysteine, NAC, Alcohol Dependence, N-acetylcysteine
Eligibility Criteria
Inclusion Criteria:
- Alcohol Use Disorder according to the DSM-V criteria
- A desire to reduce or stop drinking
- Consumed at least 21 standard drinks per week or 2 heavy drinking days per week (HDD: ≥ 5 standard drinks/day for men; ≥4 for women) in the month prior to screening
- Adequate cognition and English language skills to give valid consent and complete research interviews
- Stable housing
- Willingness to give written informed consent
Exclusion Criteria:
- Pregnancy or lactation (women will be advised to use reliable contraception during the trial and a pregnancy test will be performed were necessary)
- Concurrent use of any psychotropic medication other than antidepressants (provided these are taken at stable doses for at least two months)
- Any substance dependence other than nicotine
- Clinically unstable systemic medical (e.g. cancer, end stage liver disease: e.g. MELD score ≥ 10) or psychiatric disorder (e.g. active psychosis, borderline personality disorder, active suicide risk: e.g. MADRAS item 10 score of 6) that precludes trial participation
- Concurrent use of selenium, vitamin D or other anti-oxidants
- Any alcohol pharmacotherapy within the past month
Sites / Locations
- Drug Health Services, Royal Prince Alfred HospitalRecruiting
- Cornwall Street Medical Centre (UQ Health Care)
- Turning Point
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
N-acetyl Cysteine
Placebo
Arm Description
Generic name: N-acetyl cysteine. Brand: ACC-600 (Acetylcysteine). Strength: 600mg per capsule. Form: capsule Route: oral Frequency: 2x capsules twice per day = total 4 capsules/day Duration: 12 weeks + Standard of Care: Medical Management.
Matched placebo Generic name: dicalcium phosphate Strength: 600mg per capsule Form: capsule Route: oral Frequency: 2x capsules twice per day = total 4 capsules/day Duration: 12 weeks. + Standard of Care: Medical Management.
Outcomes
Primary Outcome Measures
Heavy Drinking Days
Reduction in Heavy Drinking Days (HDD; defined as 4 or more drinks in a day for women and five or more drinks in a day for men). This will be measured by the Timeline Follow Back and corroborated with Phosphatidylethanol (PEth) levels
Secondary Outcome Measures
Changes in Liver Function
Liver Function will be assessed through blood sample at baseline. We will measurement levels of enzyme gamma-glutamyl transferase (GGT), aspartate transaminase (AST), and alanine transaminase (ALT).
Absence of any HDD
Measured by Timeline Follow Back and corroborated with Phosphatidylethanol (PEth) levels
Full Information
NCT ID
NCT05408247
First Posted
June 2, 2022
Last Updated
March 14, 2023
Sponsor
University of Sydney
Collaborators
Monash University
1. Study Identification
Unique Protocol Identification Number
NCT05408247
Brief Title
A Randomised Controlled Trial of N-acetylcysteine for the Management of Alcohol Use Disorder
Acronym
NAC-AUD
Official Title
A Randomised Controlled Trial of N-acetylcysteine for the Management of Alcohol Use Disorder
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 16, 2023 (Actual)
Primary Completion Date
November 2025 (Anticipated)
Study Completion Date
November 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Sydney
Collaborators
Monash University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
To explore the effectiveness of n-acetylcysteine in improving treatment outcomes for alcohol use disorder in a double-blind randomised placebo-controlled trial.
Detailed Description
Australia urgently requires new treatment strategies for the treatment of alcohol dependence. Although alcohol use disorders are a leading cause of preventable death in Australia, their treatment is generally not evidence based. The medications currently approved for use in Australia for the management of alcohol dependence have limited efficacy, and existing research does not address the heterogeneity of treatment response. Targeted personalised medicine addresses this heterogeneity with better medicine selection for patients based on their genotype and clinical comorbidities.
Following on from a recent pilot study conducted by CI Morley (NCT03879759), this project will evaluate the clinical efficacy and tolerability of NAC, relative to a placebo, in heavy drinkers. We hypothesise that NAC-treated participants will be better able to achieve a reduction in heavy drinking. We will utilise a double-blind, randomised, controlled design. A sample of 280 individuals will receive 12 weeks of treatment with NAC (2400 mg/day) or placebo.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcohol Use Disorder (AUD)
Keywords
N-acetyl Cysteine, NAC, Alcohol Dependence, N-acetylcysteine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double-blind design
Allocation
Randomized
Enrollment
280 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
N-acetyl Cysteine
Arm Type
Experimental
Arm Description
Generic name: N-acetyl cysteine. Brand: ACC-600 (Acetylcysteine). Strength: 600mg per capsule. Form: capsule Route: oral Frequency: 2x capsules twice per day = total 4 capsules/day Duration: 12 weeks
+ Standard of Care: Medical Management.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matched placebo
Generic name: dicalcium phosphate Strength: 600mg per capsule Form: capsule Route: oral Frequency: 2x capsules twice per day = total 4 capsules/day Duration: 12 weeks.
+ Standard of Care: Medical Management.
Intervention Type
Drug
Intervention Name(s)
N-acetyl cysteine
Other Intervention Name(s)
NAC
Intervention Description
2400mg/day
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matched placebo
Primary Outcome Measure Information:
Title
Heavy Drinking Days
Description
Reduction in Heavy Drinking Days (HDD; defined as 4 or more drinks in a day for women and five or more drinks in a day for men). This will be measured by the Timeline Follow Back and corroborated with Phosphatidylethanol (PEth) levels
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Changes in Liver Function
Description
Liver Function will be assessed through blood sample at baseline. We will measurement levels of enzyme gamma-glutamyl transferase (GGT), aspartate transaminase (AST), and alanine transaminase (ALT).
Time Frame
24 weeks
Title
Absence of any HDD
Description
Measured by Timeline Follow Back and corroborated with Phosphatidylethanol (PEth) levels
Time Frame
24 weeks
Other Pre-specified Outcome Measures:
Title
Cost-Efficacy
Description
Examine the cost-efficacy between NAC and placebo from both health sector and societal perspectives. Measured by Disability-Adjusted Life Years (DALYs)
Time Frame
12 weeks
Title
Changes in Alcohol Craving
Description
As measured by the Alcohol Craving Experience Questionnaire (ACEQ). Higher scores indicate more severe craving.
Time Frame
24 weeks
Title
Mean alcohol consumption per drinking day
Description
Measured by Timeline Follow Back and corroborated with Phosphatidylethanol (PEth) levels
Time Frame
24 weeks
Title
Change in dependence Severity
Description
Measured by the Alcohol Dependence Scale. The minimum score is 0 and the maximum score is 47. A higher score indicates more severe dependence.
Time Frame
24 weeks
Title
Changes in Anxiety
Description
Measured by cumulative scores on the DASS-21 Anxiety Scale. This scale has a minimum score of 0 and maximum score of 21. A higher score indicates more anxiety.
Time Frame
24 weeks
Title
Changes in Depression
Description
Measured by cumulative scores on the DASS-21 Depression Scale. This scale has a minimum score of 0 and maximum score of 21. A higher score indicates greater depression.
Time Frame
24 weeks
Title
Changes in Stress
Description
Measured by cumulative scores on the DASS-21 Stress Scale. This scale has a minimum score of 0 and maximum score of 21. A higher score indicates more stress.
Time Frame
24 weeks
Title
Sleep Disturbances
Description
As measured by the ISI (Insomnia Severity Index). This Index has a minimum score of 0 and a maximum score of 28. The higher the score indicates more severe insomnia.
Time Frame
24 weeks
Title
Lifetime Consequences related to Drinking
Description
To examine the adverse consequences a participant has experienced in their lifetime due to alcohol abuse in five areas: Interpersonal, Physical, Social, Impulsive, and Intrapersonal. This is measured using the Drinker Inventory of Consequences Lifetime Edition (DrInC-2L). Higher scores indicate more consequences.
Time Frame
Baseline
Title
Recent Consequences related to Drinking
Description
To examine the adverse consequences a participant has experienced in the last 3 months due to alcohol abuse in five areas: Interpersonal, Physical, Social, Impulsive, and Intrapersonal. This is measured using the Drinker Inventory of Consequences Recent Edition (DrInC-2R). Higher scores indicate more consequences.
Time Frame
12 weeks
Title
Changes in Consequences related to Drinking
Description
To examine the change in adverse consequences a participant has experienced across the trial due to alcohol abuse in five areas: Interpersonal, Physical, Social, Impulsive, and Intrapersonal. This is measured by comparing the Drinker Inventory of Consequences Recent Edition (DrInC-2R) and the Drinker Inventory of Consequences Lifetime Edition (DrInC-2L). Higher scores indicate more consequences.
Time Frame
24 weeks
Title
Drinking Dairy
Description
Daily texts will be sent out to participants querying the amount of alcohol they have consumed. Participant responses to this will be recorded. This will be managed through SEMA software.
Time Frame
12 weeks
Title
Nicotine Dependence
Description
Measured by the Fagerstrom Test for Nicotine Dependence (FTND). This test has a minimum score of 0 and a maximum score of 10. Higher scores indicate a more intense physical dependence on nicotine.
Time Frame
Baseline
Title
Changes in Suicidal Ideation
Description
As measured by the Suicidal Ideation Attributes Scale (SIDAS). This scale has a minimum score of 0 and a maximum score of 50. Higher scores indicate more severe suicidal thoughts.
Time Frame
24 weeks
Title
Changes in Information Gathering ability
Description
As measured by the Caravan Spotter task of the Cognitive Impulsivity Suite (CIS). This measures information gathering through a perceptual decision making task whereby the target is initially ambiguous but progressively becomes clearer.
Time Frame
24 weeks
Title
Changes in Attentional Control
Description
As measured by the Bounty Hunter task of the Cognitive Impulsivity Suite (CIS). This measures attentional control using a Go/No Go task.
Time Frame
24 weeks
Title
Changes in Monitoring of Feedback
Description
As measured by the Prospectors Gamble task of the Cognitive Impulsivity Suite (CIS). This involves a probabilistic reverse learning task to measure monitoring of feedback.
Time Frame
24 weeks
Title
Irritability
Description
As measured by the Brief Irritability Test (BITe). This test has a minimum score of 0 and a maximum score of 30. Higher scores indicate greater irritability.
Time Frame
Baseline
Title
Changes in Physical Activity
Description
To assess an individuals' health based on the previous 7 days of physical activity. This is measured by the International Physical Activity Questionnaire (IPAQ-Long). We are interested in whether across treatment, answers to this questionnaire will change.
Time Frame
24 weeks
Title
Changes in Quality of Life
Description
To assess whether treatment can change quality of life as measured by the short form Health Survey (SF-36). This survey has 36 items that measure 8 domains of health, including: physical functioning, physical role limitations, bodily pain, general health perceptions, energy/vitality, social functioning, emotional role limitations and mental health. The scores are transformed to range from 0 (worst possible health) to 100 (best possible health).
Time Frame
24 weeks
Title
Changes in Quality of Life
Description
As measured by the EQ-5D-5L. This instrument measures 5 different domains of life including: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each domain is assessed by one question. This instrument has a minimum score of 0 (worst possible health) and a maximum score of 1 (best possible health).
Time Frame
24 weeks
Title
Changes in ability to inhibit prepotent responses
Description
As measured by the Stroop Colour Word Test. This test measures ability to inhibit prepotent responses and processing speed. This is assessed through the time it takes for an individual to appropriately select an incongruent response. For example, selecting "black" for the word "black" that is coloured in "green". Higher scores indicate worse performance.
Time Frame
24 weeks
Title
Changes in processing speed
Description
As measured by the Trail Making Task (TMT). This test measures the ability to an individual to process visual stimuli, as measured in time. In the TMT Part A, individuals are instructed to draw a line between numbers, 1-2-3-4-5. Higher time indicates slower processing speed. In the TMT Part B individuals are instructed to switch between drawing lines between numbers and letters, for example 1-A-2-B-3-C. Higher time indicates worse processing speed and switching ability.
Time Frame
24 weeks
Title
Changes in DSM-5 PTSD symptomology
Description
As measured by the PCL-5. This self-report questionnaire lists 20-items that assess DSM-5 PTSD criteria. A higher score indicates greater severity
Time Frame
24 weeks
Title
Changes in use of Health Services
Description
As measured by the Brief Health Services Use Questionnaire. This questionnaire assesses Health Service Use across the last 3 months.
Time Frame
24 weeks
Title
Hangover Diary
Description
Daily texts will be sent out to participants querying the hangover symptoms they are experiencing, if any. Participant responses to this will be recorded. This will be managed through SEMA software.
Time Frame
12 weeks
Title
Using Redox Markers to predict treatment response
Description
We will use blood samples collected at baseline to measure redox markers (GPxBC, GSHBC). At the end of treatment we will see whether these markers are predictive of treatment response
Time Frame
Baseline
Title
Changes in Redox Markers
Description
We will use blood samples collected at baseline and wk 12 to measure changes in redox markers (GPxBC, GSHBC)
Time Frame
12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Alcohol Use Disorder according to the DSM-V criteria
A desire to reduce or stop drinking
Consumed at least 21 standard drinks per week or 2 heavy drinking days per week (HDD: ≥ 5 standard drinks/day for men; ≥4 for women) in the month prior to screening
Adequate cognition and English language skills to give valid consent and complete research interviews
Stable housing
Willingness to give written informed consent
Exclusion Criteria:
Pregnancy or lactation (women will be advised to use reliable contraception during the trial and a pregnancy test will be performed were necessary)
Concurrent use of any psychotropic medication other than antidepressants (provided these are taken at stable doses for at least two months)
Any substance dependence other than nicotine
Clinically unstable systemic medical (e.g. cancer, end stage liver disease: e.g. MELD score ≥ 10) or psychiatric disorder (e.g. active psychosis, borderline personality disorder, active suicide risk: e.g. MADRAS item 10 score of 6) that precludes trial participation
Concurrent use of selenium, vitamin D or other anti-oxidants
Any alcohol pharmacotherapy within the past month
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kirsten Morley, PhD
Phone
61295153636
Email
Kirsten.morley@sydney.edu.au
First Name & Middle Initial & Last Name or Official Title & Degree
Paul Haber, MBBS
Email
paul.haber@sydney.edu.au
Facility Information:
Facility Name
Drug Health Services, Royal Prince Alfred Hospital
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kirsten Morley
Email
Kirsten.morley@sydney.edu.au
First Name & Middle Initial & Last Name & Degree
Paul Haber
Facility Name
Cornwall Street Medical Centre (UQ Health Care)
City
Annerley
State/Province
Queensland
ZIP/Postal Code
4103
Country
Australia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Paul Clark, MBBS
Email
paul.j.clark@uq.edu.au
First Name & Middle Initial & Last Name & Degree
Paul Clark, MBBS
Facility Name
Turning Point
City
Richmond
State/Province
Victoria
ZIP/Postal Code
3121
Country
Australia
Individual Site Status
Active, not recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Randomised Controlled Trial of N-acetylcysteine for the Management of Alcohol Use Disorder
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