Effect of N-acetylcysteine on Alcohol and Cocaine Use Disorders: A Double-Blind Randomized Controlled Trial.

Phase 4

• Conditions: Cocaine Addiction; Alcohol Addiction
• Interventions: Drug: Alcohol Placebo; Drug: Cocaine N-acetylcysteine; Drug: Cocaine Placebo; Drug: Alcohol N-acetylcysteine

• Registration Number: NCT03018236
• Lead Sponsor: Hospital de Clinicas de Porto Alegre

Brief Summary

This study evaluates the use of N-acetylcysteine in the treatment of alcohol and cocaine use disorders. Alcohol users will be split in two groups, one will receive the active N-acetylcysteine and the other placebo. The same division will occur with cocaine users. The effects of N-acetylcysteine in adherence, abstinence, psychiatric symptoms and stress biomarkers will be evaluated.

Detailed Description

N-acetylcysteine acts replenishing the human body glutathione storages. Glutathione is an important antioxidant agent, and also modulates the N-methyl-D-aspartate (NMDA) glutamatergic receptor. Glutamate has been associated with the neuroadaptation related to substance use disorders, and thus it is considered a potential target for pharmacological interventions regarding these disorders. N-acetylcysteine also interacts with the cystine-glutamate antiporter on astrocytes hence increasing glutamate release into the extracellular space.

N-acetylcysteine effects and its implications in the addiction disorders have been studied initially with animal models. Glutamate levels normalization through N-acetylcysteine reduced compulsive drug self-administration and drug-seeking behavior in mice. In addition, there are promising results also with human subjects, showing benefits for cocaine, alcohol and cannabis use disorders.

This study consists of a randomized, double-blind, placebo controlled trial with four arms: alcohol users divided into NAC vs Placebo and cocaine users divided into NAC vs Placebo.

Study Timeline

• Status Verified: 2017-01
• Study Start: 2017-01
• Study First Submitted: 2017-01-10
• Study First Submitted QC: 2017-01-10
• Study First Posted: 2017-01-11
• Last Update Submitted: 2017-01-20
• Last Update Posted: 2017-01-24
• Primary Completion: 2018-07
• Study Completion: 2018-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Male
• Target Recruitment: 100

Inclusion Criteria

• Diagnostic of Alcohol or Cocaine Use Disorder
• Seven days of inpatient treatment in an addiction treatment specialized unit

Exclusion Criteria

• Another Substance Use Disorder (exception: tobacco)
• Severe medical conditions (cardiac, renal or hepatic), that preclude subject participation
• History of asthma or convulsions medication use
• Recent use (<14 days) of any medication that could interfere with the study medication
• History of anaphylactic reactions with the study medication
• Suicide risk
• Inability to understand the informed consent form or to comply with the study requirements
• Any severe neuropsychiatric condition, not caused by the substance use, that requires specific medication treatments and could interfere with the study development, in the investigators opinion (for instance: dementia, schizophrenia or other psychoses, multiple sclerosis, severe depression, stroke, epilepsy, bipolar disorder)
• Failing to complete the screening procedures prior to the study first week

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Alcohol Placebo	Alcohol Placebo	A placebo capsule matching color and smell of the active medication
Cocaine N-acetylcysteine	Cocaine N-acetylcysteine	600 mg N-acetylcysteine capsule by mouth, every 12 hours for 8 weeks
Cocaine Placebo	Cocaine Placebo	A placebo capsule matching color and smell of the active medication
Alcohol N-acetylcysteine	Alcohol N-acetylcysteine	600 mg N-acetylcysteine capsule by mouth, every 12 hours for 8 weeks

Primary Outcome Measures

Name	Time	Method
Number of participants who attended all study appointments	8 weeks	Completers (i.e. subjects who attended all study appointments) vs non-completers

Secondary Outcome Measures

Name	Time	Method
TBARS	8 weeks	Differences between groups regarding dosage of Thiobarbituric Acid Reactive Substances (TBARS)
Abstinence by urine	8 weeks	Amount of positive urine tests for cocaine users
BDNF	8 weeks	Differences between groups regarding dosage of Brain Derived Neurotrophic Factor (BDNF)
CAT	8 weeks	Differences between groups regarding dosage of Catalase (CAT)
Carbonyl	8 weeks	Differences between groups regarding dosage of Carbonyl
Change in scores of CGI	8 weeks	Differences in scores of the Clinical Global Impression (CGI)
Change in scores of FAST	8 weeks	Differences in scores of the Functioning Assessment Short Test (FAST).
Abstinence by self report	8 weeks	Timeline Followback Method
Days of inpatient treatment	Up to 4 weeks	The difference (if any) between placebo and intervention groups in the amount of inpatient treatment days.
GSSG	8 weeks	Differences between groups regarding dosage of Oxidized Glutathione (GSSG)
GSH	8 weeks	Differences between groups regarding dosage of Glutathione (GSH)
GPx	8 weeks	Differences between groups regarding dosage of Glutathione Peroxidase (GPx)
Anxiety symptoms	8 weeks	Differences in scores of the Beck Anxiety Inventory (BAI)
SOD	8 weeks	Differences between groups regarding dosage of Superoxide Dismutase (SOD)
Abstinence by breathalyzer	8 weeks	Amount of positive breathalyzer tests for alcohol users
Depressive symptoms	8 weeks	Differences in scores of the Beck Depression Inventory (BDI)

Trial Locations

Locations (1)

Hospital de Clinicas de Porto Alegre - Unidade Alvaro Alvim; 🇧🇷 Porto Alegre, RS, Brazil