Evaluating the Hypothesized Mechanism of Action of N-acetylcysteine for Bipolar Disorder

Study Overview
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Brief Summary
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This research study evaluates the effects of anFDA-approved medication NAC in individuals with Bipolar Disorder. Participants in the study will will be assigned to two medication conditions and will take both NAC and a matched placebo. The order in which they take each medication will be random. Study medication will be taken for 14 days. There will be 5 study visits, with 2 MRI brain imaging scans completed. Questionnaires and clinical interview measures will be completed at study visits along with consistent assessment of potential side effects from study medication.

Official Title
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Experimentally Evaluating the Hypothesized Mechanism of Action of N-acetylcysteine for Bipolar Disorder

Conditions
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Bipolar Disorder, Bipolar I Disorder, Bipolar II Disorder

Intervention / Treatment
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* Drug: N-Acetyl cysteine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages 18-60 years Meet DSM-5 criteria for bipolar I or II disorder Able to provide informed consent and read, understand, and accurately complete assessment instruments Willing to commit to medication treatment and follow-up assessments Meets DSM-5 criteria for any mood episode (i.e., Major Depressive, Hypomanic, Manic), Current or In Partial Remission Prescribed daily use of at least one FDA-approved mood stabilizing medication (i.e., lithium, divalproex sodium, lamotrigine, 2nd generation antipsychotic) Willing to abstain from antioxidant supplements (e.g., coenzyme Q-10, vitamin E) for the duration of the study. Exclusion Criteria: A primary psychiatric diagnosis other than BD (e.g., Schizophrenia) Meet DSM-5 criteria for substance use disorder (other than Tobacco Use Disorder) within the past 6 months. Any uncontrolled neurological condition (e.g., epilepsy) that could confound the results of the study Any history of brain injury with loss of consciousness greater than 5 minutes Any history of mental retardation, dementia, or recent electroconvulsive therapy (in the past 3 months) Any uncontrolled medical condition that may adversely affect the conduct of the study or jeopardize the safety of the participant Hepatocellular disease as indicated by plasma levels of liver transaminases (aspartate transaminase, alanine transaminase) greater than 3 times the normal range Renal insufficiency as indicated by plasma levels of creatinine greater than 2 times the normal range Concomitant use of nitroglycerine, carbamazepine, or any other medication deemed to be hazardous if taken with N-Acetylcysteine (NAC). Medication dose changes of ≥ 20% ≤ 2 weeks prior to testing Women of childbearing potential who are pregnant, lactating, or refuse adequate forms of contraception Current suicidal or homicidal risk Baseline scores greater than 35 on the Montgomery-Asberg Depression Rating Scale or greater than 25 on the Young Mania Rating Scale Has taken NAC in the last month or experienced adverse effects/allergic reaction from it at any time Significant claustrophobia and/or past negative experiences with MRI Presence of non-MRI safe materials in the body (e.g., ferrous metal implants, pacemaker)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A: NAC, then Placebo Oral Capsule<br>Group A will receive NAC 2 times a day for a total of 14 days. On Day 14 they will have a Magnetic Resonance Imaging (MRI) exam. They will then have a 14 day washout period. They will then receive Placebo Oral Capsule 2 times a day for 14 days and have another MRI exam on day 14. | Drug: N-Acetyl cysteine<br>* Group A and Group B will receive N-Acetylcysteine (NAC). Group A will receive NAC as their first 14 day condition and Group B will receive NAC as their second 14 day condition. Participants will take NAC for 14 days and then have a MRI exam after completing various assessments (clinical interview, questionnaires, etc).<br>Drug: Placebo<br>* Group A and Group B will receive Placebo. Group A will receive Placebo as their first 14 day condition and Group B will receive Placebo as their second 14 day condition. Participants will take Placebo Oral Capsule for 14 days and then have a MRI exam after completing various assessments (clinical interview, questionnaires, etc).<br>|
| Experimental: Group B: Placebo Oral Capsule, then NAC<br>Group A will receive Placebo Oral Capsule 2 times a day for a total of 14 days. On Day 14 they will have a Magnetic Resonance Imaging (MRI) exam. They will then have a 14 day washout period. They will then receive NAC 2 times a day for 14 days and have another MRI exam on day 14. | Drug: N-Acetyl cysteine<br>* Group A and Group B will receive N-Acetylcysteine (NAC). Group A will receive NAC as their first 14 day condition and Group B will receive NAC as their second 14 day condition. Participants will take NAC for 14 days and then have a MRI exam after completing various assessments (clinical interview, questionnaires, etc).<br>Drug: Placebo<br>* Group A and Group B will receive Placebo. Group A will receive Placebo as their first 14 day condition and Group B will receive Placebo as their second 14 day condition. Participants will take Placebo Oral Capsule for 14 days and then have a MRI exam after completing various assessments (clinical interview, questionnaires, etc).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in dACC GSH levels through Proton Magnetic Resonance Spectroscopy | Brain GSH levels in dorsal anterior cingulate measured via Proton Magnetic Resonance Spectroscopy | Day 14 of each experimental condition |