N-Acetylcysteine for Bipolar and Alcohol Use Disorders
N-acetylcysteine for Restoring Glutamate/Glutathione Homeostasis and Reducing Heavy Drinking in Co-occurring Bipolar and Alcohol Use Disorders
This study will evaluate N-acetylcysteine (NAC) in adults with bipolar disorder and alcohol use disorder. Participants will be randomly assigned to receive NAC or matched placebo for 28 days. The study includes five visits and three MRI brain imaging scans. Questionnaires, clinical interviews, alcohol and drug assessments, laboratory testing, and monitoring for possible side effects will be completed during study visits.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This randomized, placebo-controlled, double-blind, parallel-group mechanistic clinical trial will evaluate adjunctive N-acetylcysteine (NAC) in adults with co-occurring bipolar disorder and alcohol use disorder. The study is designed to examine whether NAC changes dorsal anterior cingulate cortex glutamate and glutathione homeostasis and brain activation to alcohol cues, and whether those changes are associated with reductions in heavy drinking and depressive symptoms. Participants will complete a baseline evaluation, a pretreatment MRI visit, MRI visits at 14 and 28 days after treatment begins, and a safety visit within 72 hours after the day 28 visit. Study procedures include clinical interviews, self-report questionnaires, alcohol and drug assessments, blood and urine collection, and proton magnetic resonance spectroscopy and functional MRI. Treatment assignment details, intervention records, and outcome-measure records are intentionally left for study-team completion.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Sara Hix
- Phone Number: 843-792-0572
- Email: hixs@musc.edu
Study Locations
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South Carolina
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Charleston, South Carolina, United States, 29425
- Medical University of South Carolina
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Contact:
- Sara Hix
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age 18 to 60 years.
- Meet DSM-5 criteria for bipolar I or bipolar II disorder.
- Prescribed daily use of at least one FDA-approved mood-stabilizing medication (lithium, divalproex sodium, lamotrigine, or a second-generation antipsychotic).
- Meet DSM-5 criteria for current, within the past 90 days, moderate to severe alcohol use disorder.
- Active alcohol use in the past 14 days, with heavy drinking days on at least 50% of drinking days in the past 30 days.
- Able to provide informed consent and read, understand, and accurately complete assessment instruments.
- Willing to commit to medication treatment and follow-up assessments.
- Willing to abstain from antioxidant supplements for the duration of the study.
Exclusion Criteria:
- Primary psychiatric diagnosis other than bipolar disorder.
- Uncontrolled neurological condition that could confound study results.
- History of brain injury with loss of consciousness greater than 5 minutes.
- History of intellectual disability or dementia.
- Uncontrolled medical condition that may adversely affect study conduct or participant safety.
- Hepatocellular disease as defined in the protocol.
- Renal insufficiency as defined in the protocol.
- Concomitant use of nitroglycerin, carbamazepine, or another medication deemed hazardous with NAC.
- Concomitant use of specified alcohol-use-disorder medications or medications that could interfere with glutamate transmission.
- Electroconvulsive therapy in the past 3 months.
- Medication dose change of 20% or greater within 2 weeks before testing.
- Pregnancy, lactation, or refusal to use adequate contraception when applicable.
- Current suicidal or homicidal risk.
- Baseline MADRS score greater than 35 or YMRS score greater than 25.
- Clinically significant alcohol withdrawal symptoms or autonomic instability.
- NAC use in the last month or prior adverse effects from NAC.
- Has an allergy to riboflavin
- Significant claustrophobia or prior negative experience with MRI.
- Non-MRI-safe material in the body.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Group A - N-Acetylcysteine
After group assignment but before taking any study medication, participants will have a Magnetic Resonance Imaging (MRI) exam after completing various assessments (clinical interview, questionnaires, etc.). Group A will receive N-Acetylcysteine (NAC) 2 times a day for a total of 28 days. They will have follow up MRIs on day 14 and 28. |
28 days of NAC taken 2 times per day with MRI on days 1 (pre medication dosing), 14, and 28 |
|
Placebo Comparator: Group B - Placebo
After group assignment but before taking any study medication, participants will have a Magnetic Resonance Imaging (MRI) exam after completing various assessments (clinical interview, questionnaires, etc.). Group B will receive Placebo 2 times a day for a total of 28 days. They will have follow up MRIs on day 14 and 28. |
28 days of Placebo taken 2 times per day with MRI on days 1 (pre medication dosing), 14, and 28 |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Change in dACC glutamate/glutathione levels through Proton Magnetic Resonance
Time Frame: Baseline to end of treatment, approximately 28 days
|
Concentrations of glutamate and glutathione in the dorsal anterior cingulate cortex will be measured on day 1, 14, and 28. |
Baseline to end of treatment, approximately 28 days
|
Collaborators and Investigators
Investigators
- Principal Investigator: James J. Prisciandaro, Ph.D., Medical University of South Carolina
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- Pro00153022
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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