Bipolar Disorder, Bipolar I Disorder, Bipolar II Disorder
Conditions
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.
Interventions
DRUGN-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).
DRUGPlacebo
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).
Sponsors
Milken Institute
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Double-blind
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in dACC GSH Levels Through Proton Magnetic Resonance Spectroscopy | Day 14 of each experimental condition | Brain GSH levels, balanced with water and CSF-corrected, in dorsal anterior cingulate measured via Proton Magnetic Resonance Spectroscopy |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A: N-Acetylcysteine, Washout, Then Placebo Oral Capsule Two, 2-week conditions.
Week 1 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), maximum dose of NAC (i.e., 3g/day NAC) (Days 1-14), MRI (Day 14) and medication washout (Day 15-28).
N-Acetylcysteine: 14 day trial of 3g NAC.
Week 2 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), maximum dose of matched Placebo Oral Capsule (Days 1-14), and MRI (Day 14).
Placebo Oral Capsule: 14 day trial of matched placebo. | 6 |
| Group B: Placebo Oral Capsule, Washout, Then N-Acetylcysteine Two, 2-week conditions.
Week 1 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), maximum dose of matched Placebo Oral Capsule (Days 1-14), MRI (Day 14) and medication washout (Day 15-28).
Placebo Oral Capsule: 14 day trial of matched placebo.
Week 2 condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), maximum dose of NAC (i.e., 3g/day NAC) (Days 1-14), and MRI (Day 14).
N-Acetylcysteine: 14 day trial of 3g NAC. | 6 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Group A: N-Acetylcysteine, Washout, Then Placebo Oral Capsule | Group B: Placebo Oral Capsule, Washout, Then N-Acetylcysteine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 6 Participants | 12 Participants |
| Age, Continuous | 34.5 years | 41.33 years | 37.92 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 6 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 5 Participants | 10 Participants |
| Region of Enrollment United States | 6 participants | 6 participants | 12 participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 10 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 11 | 0 / 12 |
| other Total, other adverse events | 1 / 12 | 1 / 11 | 1 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 11 | 0 / 12 |
Outcome results
Primary
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
Time frame: Day 14 of each experimental condition
Population: Overall number of participants analyzed includes participants who completed full study protocol (i.e. 2, 2-week medication trials and 1, 2-week washout period). Two participants have been removed from outcome measure data (1 - participant lost to follow up and did not complete placebo condition, 1 - participant's MRI data was unusable due to excessive head motion). Data from these 2 participants has been included in other portions of this study record (Adverse Events, Demographics, etc).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| N-Acetylcysteine | Change in dACC GSH Levels Through Proton Magnetic Resonance Spectroscopy | 2.426 Institutional Units | Standard Deviation 0.341 |
| Placebo | Change in dACC GSH Levels Through Proton Magnetic Resonance Spectroscopy | 2.207 Institutional Units | Standard Deviation 0.423 |