A Randomised Controlled Trial of N-acetylcysteine for the Management of Alcohol Use Disorder

Alcohol Use Disorder (AUD) Clinical Trial

— NAC-AUD  

Official title:

A Randomised Controlled Trial of N-acetylcysteine for the Management of Alcohol Use Disorder

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05408247
• Other study ID #: X21-0342
• Status: Recruiting
• Phase: Phase 4
• Start date: February 16, 2023
• Est. completion date: November 2026

Study information

• Verified date: March 2023
• Source: University of Sydney
• Contact: Kirsten Morley, PhD
• Phone: 61295153636
• Email: Kirsten.morley[@]sydney.edu.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To explore the effectiveness of n-acetylcysteine in improving treatment outcomes for alcohol use disorder in a double-blind randomised placebo-controlled trial.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 280
• Est. completion date: November 2026
• Est. primary completion date: November 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Alcohol Drinking
• Alcohol Use Disorder (AUD)
• Alcoholism

Intervention

Drug:
• N-acetyl cysteine
2400mg/day
• Placebo
Matched placebo

Locations

Country	Name	City	State
Australia	Cornwall Street Medical Centre (UQ Health Care)	Annerley	Queensland
Australia	Turning Point	Richmond	Victoria
Australia	Drug Health Services, Royal Prince Alfred Hospital	Sydney	New South Wales

Sponsors (2)

Lead Sponsor	Collaborator
University of Sydney	Monash University

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cost-Efficacy	Examine the cost-efficacy between NAC and placebo from both health sector and societal perspectives. Measured by Disability-Adjusted Life Years (DALYs)	12 weeks
Other	Changes in Alcohol Craving	As measured by the Alcohol Craving Experience Questionnaire (ACEQ). Higher scores indicate more severe craving.	24 weeks
Other	Mean alcohol consumption per drinking day	Measured by Timeline Follow Back and corroborated with Phosphatidylethanol (PEth) levels	24 weeks
Other	Change in dependence Severity	Measured by the Alcohol Dependence Scale. The minimum score is 0 and the maximum score is 47. A higher score indicates more severe dependence.	24 weeks
Other	Changes in Anxiety	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.	24 weeks
Other	Changes in Depression	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.	24 weeks
Other	Changes in Stress	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.	24 weeks
Other	Sleep Disturbances	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.	24 weeks
Other	Lifetime Consequences related to Drinking	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.	Baseline
Other	Recent Consequences related to Drinking	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.	12 weeks
Other	Changes in Consequences related to Drinking	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.	24 weeks
Other	Drinking Dairy	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.	12 weeks
Other	Nicotine Dependence	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.	Baseline
Other	Changes in Suicidal Ideation	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.	24 weeks
Other	Changes in Information Gathering ability	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.	24 weeks
Other	Changes in Attentional Control	As measured by the Bounty Hunter task of the Cognitive Impulsivity Suite (CIS). This measures attentional control using a Go/No Go task.	24 weeks
Other	Changes in Monitoring of Feedback	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.	24 weeks
Other	Irritability	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.	Baseline
Other	Changes in Physical Activity	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.	24 weeks
Other	Changes in Quality of Life	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).	24 weeks
Other	Changes in Quality of Life	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).	24 weeks
Other	Changes in ability to inhibit prepotent responses	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.	24 weeks
Other	Changes in processing speed	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.	24 weeks
Other	Changes in DSM-5 PTSD symptomology	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	24 weeks
Other	Changes in use of Health Services	As measured by the Brief Health Services Use Questionnaire. This questionnaire assesses Health Service Use across the last 3 months.	24 weeks
Other	Hangover Diary	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.	12 weeks
Other	Using Redox Markers to predict treatment response	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	Baseline
Other	Changes in Redox Markers	We will use blood samples collected at baseline and wk 12 to measure changes in redox markers (GPxBC, GSHBC)	12 weeks
Primary	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	24 weeks
Secondary	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).	24 weeks
Secondary	Absence of any HDD	Measured by Timeline Follow Back and corroborated with Phosphatidylethanol (PEth) levels	24 weeks