Alcohol Use Disorder (AUD)
Conditions
Keywords
N-acetyl Cysteine, NAC, Alcohol Dependence, N-acetylcysteine
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.
Interventions
DRUGN-acetyl cysteine
2400mg/day
DRUGPlacebo
Matched placebo
Sponsors
Monash University
University of Sydney
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind design
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Heavy Drinking Days | 24 weeks | 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
| Measure | Time frame | Description |
|---|---|---|
| Changes in Liver Function | 24 weeks | 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 | 24 weeks | Measured by Timeline Follow Back and corroborated with Phosphatidylethanol (PEth) levels |
Other
| Measure | Time frame | Description |
|---|---|---|
| Mean alcohol consumption per drinking day | 24 weeks | Measured by Timeline Follow Back and corroborated with Phosphatidylethanol (PEth) levels |
| Change in dependence Severity | 24 weeks | Measured by the Alcohol Dependence Scale. The minimum score is 0 and the maximum score is 47. A higher score indicates more severe dependence. |
| Changes in Anxiety | 24 weeks | 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. |
| Changes in Stress | 24 weeks | 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. |
| Sleep Disturbances | 24 weeks | 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. |
| Lifetime Consequences related to Drinking | Baseline | 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. |
| Recent Consequences related to Drinking | 12 weeks | 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. |
| Changes in Consequences related to Drinking | 24 weeks | 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. |
| Drinking Dairy | 12 weeks | 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. |
| Nicotine Dependence | Baseline | 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. |
| Changes in Suicidal Ideation | 24 weeks | 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. |
| Changes in Information Gathering ability | 24 weeks | 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. |
| Cost-Efficacy | 12 weeks | Examine the cost-efficacy between NAC and placebo from both health sector and societal perspectives. Measured by Disability-Adjusted Life Years (DALYs) |
| Changes in Monitoring of Feedback | 24 weeks | 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. |
| Irritability | Baseline | 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. |
| Changes in Physical Activity | 24 weeks | 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. |
| Changes in Quality of Life | 24 weeks | 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). |
| Changes in ability to inhibit prepotent responses | 24 weeks | 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. |
| Changes in processing speed | 24 weeks | 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. |
| Changes in DSM-5 PTSD symptomology | 24 weeks | 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 |
| Changes in use of Health Services | 24 weeks | As measured by the Brief Health Services Use Questionnaire. This questionnaire assesses Health Service Use across the last 3 months. |
| Hangover Diary | 12 weeks | 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. |
| Using Redox Markers to predict treatment response | Baseline | 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 |
| Changes in Redox Markers | 12 weeks | We will use blood samples collected at baseline and wk 12 to measure changes in redox markers (GPxBC, GSHBC) |
| Changes in Attentional Control | 24 weeks | As measured by the Bounty Hunter task of the Cognitive Impulsivity Suite (CIS). This measures attentional control using a Go/No Go task. |
| Changes in Depression | 24 weeks | 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. |
| Changes in Alcohol Craving | 24 weeks | As measured by the Alcohol Craving Experience Questionnaire (ACEQ). Higher scores indicate more severe craving. |
Countries
Australia
Contacts
Primary ContactKirsten Morley, PhD
Backup ContactPaul Haber, MBBS
Outcome results
None listed