Alcohol Use Disorder
Conditions
Brief summary
This proposed pilot study aims to assess the effects of N-acetylcysteine (NAC) on alcohol use disorder (AUD). Despite promising preliminary research, no investigations to date have focused on NAC with alcohol use as the primary aim or on individuals specifically seeking treatment for AUD. The present proposal is an 7-week randomized, double-blind, placebo-controlled study of 3000mg of NAC in up to 50 participants (25 NAC, 25 placebo). The primary aim of the current study is to establish feasibility, dropout rate, and estimate the standard deviation of the outcome measures in order to estimate the required sample for a fully powered clinical trial and to refine the final measures for use in the fully powered clinical trial. Additionally, this study will explore preliminary efficacy signal of NAC.
Detailed description
Alcohol abuse is responsible for 1 in 10 deaths among working age adults in the U.S. and costs \ $249 billion annually. Currently approved medications for alcohol use disorder (AUD) exert only small to medium effects on drinking, with estimates indicating 12 to 20 drinkers need to be treated for one of them to benefit from the two leading medications, acamprosate and naltrexone. Thus, many patients do not benefit from current pharmacotherapies for AUD. N-acetylcysteine (NAC) is one promising pharmacotherapy that is well-tolerated, safe, and exhibits preliminary evidence across a number of psychiatric and neurological disorders. NAC is available over the counter, has been used all over the world for a variety of conditions, most notably for its 1985 FDA approved use as an antidote for acetaminophen overdose. The NAC dosage was selected as most prior studies in addiction have used 2400-3000mg and even studies up to 3600mg have found it was well-tolerated. Many studies using doses in this range achieved clinically significant improvements, including a study of NAC for smoking cessation which used 3000mg. 7 weeks was selected rather than 12 weeks or longer duration because this within the range of prior clinical trials of NAC (most are 8-12 weeks) and is fitting for the goals of this pilot trial seeking to establish feasibility and sample size for a larger clinical trial. It is beyond the primary aims of this study and the resources of the team to seek longer term outcomes (e.g., drinking at 6 months; https://www.fda.gov/media/91222/download).
Interventions
DRUGN-acetylcysteine
N-acetylcysteine is an FDA approved medication that is used to treat acetaminophen overdose.
DRUGPlacebo
Placebo
Sponsors
Uniformed Services University of the Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Double-blind
Intervention model description
Arm 1: n-acetylcysteine. 25 participants randomly selected Arm 2: placebo. 25 participants randomly selected
Eligibility
Sex/Gender
ALL
Age
18 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
1. Greater than or equal to 18 years of age 2. Meets DSM-V criteria for alcohol use disorder on the SCID-5 3. MHS Healthcare Beneficiary NOTE. While we are recruiting explicitly from the Addiction Treatment Services (ATS) patient population, we do not require that they are currently receiving treatment at ATS. For participants that are not currently in care we will provide them with resources to pursue psychotherapy while engaged in our study as outlined in the interview treatment questions and physical and mental health resource document.
Exclusion criteria
1. Lifetime clinical diagnosis of schizophrenia or bipolar disorder 2. Currently receiving medication for the treatment of alcohol use disorder including oral or injectable naltrexone (ReVia, Vivitrol), disulfiram (Antabuse), and acamprosate (Campral). 3. Pregnancy 4. Lack of English fluency sufficient to complete study measures. 5. Trying to get pregnant in the next 4 months. 6. Hospitalized because of alcohol use in the past 12 months. 7. History of seizures or delirium tremens. 8. History of liver disease 9. Diagnosis of a neurocognitive disorder (e.g., dementia, alzheimer's, mental retardation). 10. Individuals who were never enrolled into Addiction Treatment Services
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in drinks per drinking day | 7 weeks | Change in drinks per drinking day will be assessed with the Timeline Follow Back alcohol use assessment |
| Change in total drinking days | 7 weeks | Change in total drinking days will be assessed with the Timeline Follow Back alcohol use assessment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in alcohol cue-reactivity | 7 weeks | Change in alcohol cue-reactivity will be assessed with a task in which participants are exposed to stimuli associated with alcohol |
| Change in alcohol demand | 7 weeks | Change in alcohol demand will be assessed with the alcohol purchase task |
| Change in alcohol craving | 7 weeks | Change in alcohol craving will be assessed with the Penn Alcohol Craving Scale, a 5-item measure of craving for alcohol over the past week. Scores range from 0 to 30, higher scores indicate more alcohol craving. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in total marijuana use days | 7 weeks | Change in total marijuana use days will be assessed with the Timeline Follow Back marijuana use assessment in the subset of individuals who use marijuana. |
| Change in response inhibition | 7 weeks | Change in response inhibition will be assessed with the Stop Signal Task. |
| Change in cigarettes per day | 7 weeks | Change in cigarettes per day will be assessed with the Timeline Follow Back cigarette use assessment in the subset of individuals who use cigarettes. |
| Change in total cigarette use days | 7 weeks | Change in total cigarette use days will be assessed with the Timeline Follow Back cigarette use assessment in the subset of individuals who use cigarettes. |
| Change in working memory | 7 weeks | Change in working memory will be assessed with the N-back task (2 back and 3 back) |
| Change in executive functioning | 7 weeks | Change in executive functioning will be assessed with the Trail Making Task |
| Change in depression symptoms | 7 weeks | Change in depression symptoms will be assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS), a 10-item questionnaire assessing depression symptoms. Scores range from 0-60, higher scores indicate more depression symptoms |
| Change in anxiety symptoms | 7 weeks | Change in anxiety symptoms will be assessed with the Generalized Anxiety Disorder Screener (GAD-7), a 7-item self-report measure assessing symptoms of generalized anxiety. Scores range from 0-21, higher scores indicate more anxiety symptoms. |
Outcome results
None listed