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

• Sponsor: Medical University of South Carolina (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05340504
• Collaborator: Milken Institute (Other)
• Enrollment: 12
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 8.3
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder; Bipolar I Disorder; Bipolar II Disorder	Drug: N-Acetyl cysteine; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: Double-blind
• Primary Purpose: Treatment
• Official Title: Experimentally Evaluating the Hypothesized Mechanism of Action of N-acetylcysteine for Bipolar Disorder
• Actual Study Start Date: May 13, 2022
• Anticipated Primary Completion Date: Jan 21, 2023
• Anticipated Study Completion Date: Jan 21, 2023

Arms and Interventions

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).

Outcome Measures

Primary Outcome Measures

1. Change in dACC GSH levels through Proton Magnetic Resonance Spectroscopy [Day 14 of each experimental condition]

   Brain GSH levels in dorsal anterior cingulate measured via Proton Magnetic Resonance Spectroscopy

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical University Of South Carolina	Charleston	South Carolina	United States	29425

Sponsors and Collaborators

• Medical University of South Carolina
• Milken Institute

Investigators

• Principal Investigator: James Prisciandaro, PhD, Medical University of South Carolina

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: James J. Prisciandaro, Associate Professor, Medical University of South Carolina
• ClinicalTrials.gov Identifier: NCT05340504
• Other Study ID Numbers: 00117736
• First Posted: Apr 22, 2022
• Last Update Posted: Jul 8, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Disease; Bipolar Disorder; Acetylcysteine; N-monoacetylcystine

Study Results

No Results Posted as of Jul 8, 2022