The Efficacy and Neurobehavioural Mechanism of N-acetyl Cysteine (NAC) for Alcohol Dependence

The Efficacy and Neurobehavioural Mechanism of N-acetyl Cysteine for Alcohol Dependence: An Exploratory Pilot Study

The study will explore the efficacy and tolerability of a regimen of NAC (2400 mg) versus placebo for the treatment of alcohol dependence.

Study Overview

• Status: Unknown
• Conditions: Alcohol Dependence
• Intervention / Treatment: Drug: NAC 2400mg/day; Drug: Placebo

Detailed Description

Study 1: Relapse prevention: This is a double-blind, randomized, placebo-controlled clinical trial in which participants will receive oral NAC (2400 mg: 2x 600mg tablets twice per day) or matching placebo. Trial participants will receive either oral NAC ( dose stated above) or matching placebo for up to 4 weeks.

Study 2: Withdrawal: Trial participants will receive oral NAC (dose stated above) or matching placebo within the first 24 hours of their admission for up to 3 days.

Study 3: Participants from the relapse prevention substudy will also receive 30-minute non-invasive brain imaging session prior to and after completing the treatment regime in Study 1.

Both males and females will be recruited for the study.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kirsten Morley, PhD; Phone Number: +61295153636; Email: kirsten.morley@sydney.edu.au

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2050
      • Recruiting
      • Drug Health Services, Royal Prince Alfred Hospital
      • Contact: Kirsten M Morley, PhD; Phone Number: +61295153636; Email: kirsten.morley@sydney.edu.au
      • Contact: Central Intake Line; Phone Number: 0459877108; Email: sydneyalcoholtreatmentgroup@gmail.com
      • Principal Investigator: Kirsten Morley, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female patients between the ages of 18 and 65 meeting DSM-IV criteria for current alcohol use disorder (this is an exclusion for the healthy control sample)
• Able to understand and sign written informed consent
• Must have a stable residence and be able to identify an individual who could locate subject if needed
• Admitted for medical detoxification from alcohol (withdrawal study only)
• Blood alcohol concentration of 0.00 (if completing brain imaging session)
• Express a desire to achieve abstinence or to greatly reduce alcohol consumption (relapse prevention study only)

Exclusion Criteria:

• Clinically significant comorbidities or medical disease that might interfere with the evaluation of the study medication or present a safety concern.
• Pregnant women and women of childbearing potential who do not practice a medically acceptable form of birth control
• Women who are breastfeeding
• Dependence on any substance other than nicotine
• Court-mandated participation in alcohol treatment or pending incarceration (relapse prevention study only)
• Treatment/ingestion during the previous week of benzodiazepines or other sedative-hypnotic medications or history of recent chronic treatment with sedative-hypnotic medications (withdrawal study only)
• Dependence on any substance other than nicotine

The following exclusion criteria are only applicable to participants undergoing the brain imaging session:

• Extreme obesity
• Pregnant or have any reason to believe they are pregnant;
• Previous brain surgery;
• Ever employed as a machinist, a welder or a metal worker;
• Epilepsy
• Metal items such as pacemakers; aneurysm clips in the brain; metal dental implants; metallic fragments in the eye or anywhere else; insulin pump; metal implants; hearing aid or a prosthetic device.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; NAC - Relapse Prevention (4 wks)	Drug: NAC 2400mg/day; 2400mg/day 2 x 600mg b.d
Placebo Comparator: Arm 2; NAC - Relapse Prevention (4 wks)	Drug: Placebo; 4 matched placebo tablets/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study 1: Alcohol consumption	as measured by the number of heavy drinking days per week and number of drinks per drinking day	4 weeks
Study 1: Alcohol consumption	as measured by the abstinence rate, time to relapse and time to lapse	4 weeks
Study 2: Amount of Benzodiazepines administered	as measured by the number of benzodiazepines administered in the NAC vs placebo groups	3 days
Study 2: Amount of Benzodiazepines administered	as measured by Alcohol Withdrawal Scale (AWS) score	3 days
Study 2: Amount of Benzodiazepines administered	as measured by Visual Analogue Scale (VAS) score	3 days
Study 2: Amount of Benzodiazepines administered	as measured by Alcohol Urge Questionaire (AUQ) Score	3 days
Study 3: Markers of neural inflammation and responses to alcohol cue	as measured by differences in cortical levels of glutathione	4 weeks
Study 3: Markers of neural inflammation and responses to alcohol cue	as measured by differences in cortical levels of N-acetylaspartate	4 weeks
Study 3: Markers of neural inflammation and responses to alcohol cue	as measured by blood oxygen level dependent (BOLD) brain activation differences to alcohol cues (alcohol cue activation)	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alcohol craving	as measured by Penn Alcohol Craving Scale (PACS) score	4 weeks
Mood	as measured by Depression Anxiety Stress Scale (DASS) score	4 weeks

Collaborators and Investigators

• Sponsor: South West Sydney Local Health District
• Collaborators: National Health and Medical Research Council, Australia; University of Sydney
• Investigators: Principal Investigator: Kirsten Morley, PhD, University of Sydney; Principal Investigator: Paul S Haber, MBBS, Sydney Local Health District; Principal Investigator: Andrew Baille, PhD, Macquarie University; Principal Investigator: Warren B Logge, PhD, Sydney Local Health District

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2018
• Primary Completion (Anticipated): November 1, 2020
• Study Completion (Anticipated): November 1, 2020

Study Registration Dates

• First Submitted: March 10, 2019
• First Submitted That Met QC Criteria: March 14, 2019
• First Posted (Actual): March 19, 2019

Study Record Updates

• Last Update Posted (Actual): March 19, 2019
• Last Update Submitted That Met QC Criteria: March 14, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Alcoholism
• Other Study ID Numbers: X17-0343

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No