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

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Effect of N-acetylcysteine (NAC) on Treatment of Alcohol and Cocaine Use Disorders: A Double-Blind Randomized Controlled Trial.

Conditions
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Cocaine Addiction, Alcohol Addiction

Intervention / Treatment
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* Drug: Alcohol N-acetylcysteine
* Drug: Alcohol Placebo
* Drug: Cocaine N-acetylcysteine
* Drug: Cocaine Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alcohol N-acetylcysteine<br>600 mg N-acetylcysteine capsule by mouth, every 12 hours for 8 weeks | Drug: Alcohol N-acetylcysteine<br>* 1200 mg of NAC per day, taken in two doses, for subjects with alcohol use disorder<br>* Other names: NAC;|
| Placebo Comparator: Alcohol Placebo<br>A placebo capsule matching color and smell of the active medication | Drug: Alcohol Placebo<br>* Flour pills looking exactly the same as the active compound, for subjects with alcohol use disorder<br>|
| Experimental: Cocaine N-acetylcysteine<br>600 mg N-acetylcysteine capsule by mouth, every 12 hours for 8 weeks | Drug: Cocaine N-acetylcysteine<br>* 1200 mg of NAC per day, taken in two doses, for subjects with cocaine use disorder<br>* Other names: NAC;|
| Placebo Comparator: Cocaine Placebo<br>A placebo capsule matching color and smell of the active medication | Drug: Cocaine Placebo<br>* Flour pills looking exactly the same as the active compound, for subjects with cocaine use disorder<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants who attended all study appointments | Completers (i.e. subjects who attended all study appointments) vs non-completers | 8 weeks | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cocaine, alcohol, substance use disorders, addiction, N-acetylcysteine, randomized controlled trial