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

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

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.

Study Overview

• Status: Completed
• Conditions: Bipolar Disorder; Bipolar I Disorder; Bipolar II Disorder
• Intervention / Treatment: Drug: N-Acetyl cysteine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sara Hix; Phone Number: 843-792-0572; Email: hixs@musc.edu

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Ages 18-60 years
2. Meet DSM-5 criteria for bipolar I or II disorder
3. Able to provide informed consent and read, understand, and accurately complete assessment instruments
4. Willing to commit to medication treatment and follow-up assessments
5. Meets DSM-5 criteria for any mood episode (i.e., Major Depressive, Hypomanic, Manic), Current or In Partial Remission
6. Prescribed daily use of at least one FDA-approved mood stabilizing medication (i.e., lithium, divalproex sodium, lamotrigine, 2nd generation antipsychotic)
7. Willing to abstain from antioxidant supplements (e.g., coenzyme Q-10, vitamin E) for the duration of the study.

Exclusion Criteria:

1. A primary psychiatric diagnosis other than BD (e.g., Schizophrenia)
2. Meet DSM-5 criteria for substance use disorder (other than Tobacco Use Disorder) within the past 6 months.
3. Any uncontrolled neurological condition (e.g., epilepsy) that could confound the results of the study
4. Any history of brain injury with loss of consciousness greater than 5 minutes
5. Any history of mental retardation, dementia, or recent electroconvulsive therapy (in the past 3 months)
6. Any uncontrolled medical condition that may adversely affect the conduct of the study or jeopardize the safety of the participant
7. Hepatocellular disease as indicated by plasma levels of liver transaminases (aspartate transaminase, alanine transaminase) greater than 3 times the normal range
8. Renal insufficiency as indicated by plasma levels of creatinine greater than 2 times the normal range
9. Concomitant use of nitroglycerine, carbamazepine, or any other medication deemed to be hazardous if taken with N-Acetylcysteine (NAC).
10. Medication dose changes of ≥ 20% ≤ 2 weeks prior to testing
11. Women of childbearing potential who are pregnant, lactating, or refuse adequate forms of contraception
12. Current suicidal or homicidal risk
13. Baseline scores greater than 35 on the Montgomery-Asberg Depression Rating Scale or greater than 25 on the Young Mania Rating Scale
14. Has taken NAC in the last month or experienced adverse effects/allergic reaction from it at any time
15. Significant claustrophobia and/or past negative experiences with MRI
16. Presence of non-MRI safe materials in the body (e.g., ferrous metal implants, pacemaker)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: NAC, then Placebo Oral Capsule; 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; 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).; Drug: Placebo; 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).
Experimental: Group B: Placebo Oral Capsule, then NAC; 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; 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).; Drug: Placebo; 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).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: Milken Institute
• Investigators: Principal Investigator: James Prisciandaro, PhD, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2022
• Primary Completion (Actual): June 21, 2023
• Study Completion (Actual): June 21, 2023

Study Registration Dates

• First Submitted: April 15, 2022
• First Submitted That Met QC Criteria: April 15, 2022
• First Posted (Actual): April 22, 2022

Study Record Updates

• Last Update Posted (Estimated): July 24, 2023
• Last Update Submitted That Met QC Criteria: July 20, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Bipolar and Related Disorders; Bipolar Disorder; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: 00117736

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No