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

NCT05340504 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 00117736
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Bipolar Disorder; Bipolar I Disorder; Bipolar II Disorder

Outcome Measures

Primary Outcomes (1)

• Change in dACC GSH Levels Through Proton Magnetic Resonance Spectroscopy

  Brain GSH levels, balanced with water and CSF-corrected, in dorsal anterior cingulate measured via Proton Magnetic Resonance Spectroscopy

  Day 14 of each experimental condition

Study Arms (2)

Group A: N-Acetylcysteine, then Washout, then Placebo Oral Capsule

EXPERIMENTAL

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; Drug: Placebo

Group B: Placebo Oral Capsule, then Washout, then N-Acetylcysteine

EXPERIMENTAL

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; Drug: Placebo

Interventions

N-Acetyl cysteine DRUG

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).

Group A: N-Acetylcysteine, then Washout, then Placebo Oral Capsule; Group B: Placebo Oral Capsule, then Washout, then N-Acetylcysteine

Placebo DRUG

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).

Group A: N-Acetylcysteine, then Washout, then Placebo Oral Capsule; Group B: Placebo Oral Capsule, then Washout, then N-Acetylcysteine

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Medical University of South Carolina: lead
• Milken Institute: collaborator

Study Sites (1)

Medical University Of South Carolina

Charleston, South Carolina, 29425, United States

Location

MeSH Terms

Conditions

Bipolar Disorder

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: James J. Prisciandaro, Ph.D.
• Organization: Medical University of South Carolina

priscian@musc.edu

843-792-1433

Study Officials

• James Prisciandaro, PhD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: April 15, 2022
• First Posted: April 22, 2022
• Study Start: May 13, 2022
• Primary Completion: June 21, 2023
• Study Completion: June 21, 2023
• Last Updated: June 26, 2024
• Results First Posted: June 26, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)