Depression, Self-Harm, Suicide
Conditions
Brief summary
To measure NAC-induced changes to concentrations of glutathione (GSH) in the anterior cingulate cortex (ACC) as measured by magnetic resonance spectroscopy (MRS) in 36 adolescents and young adults with NSSI (12 in each group: high, low, and placebo).
Detailed description
This study is a double-blind, placebo controlled, 4-week course of two-tiered N-acetylcysteine (NAC) dosing focused on identifying the optimal dose to achieve meaningful change in measurable biomarkers (glutathione and glutamate). This design will allow us to confirm acute biological changes, select the optimal dose for achieving biological effects, and examine dose/concentration-response relationships with respect to biological markers and pharmacokinetics. Brief schedule of activities: Subjects will be recruited through community and clinical settings and screened over the phone. There will be a total of 4 in-person visits and two sets of on-line study activities. Eligible participants will be assigned to one of 3 groups (double-blinded): a low-dose NAC group (3600 mg/day), a high-dose NAC group (5400mg/day), and placebo (PBO). The study intervention period is 4 weeks. Total participation is up to 8 weeks, depending on the length of time between Day 0 and Day 1. The investigators will recruit 36 adolescents and young adults aged 16-24 years. There will be 12 participants in each group (PBO, 3600mg/day, 5400mg/day). The investigators will use a minimization procedure to ensure that the participants in these 3 groups will have similar age, clinical severity and medication status.
Interventions
DRUGN-acetyl cysteine
3600 or 5400 mg/day N-acetyl cysteine
DRUGPlacebo oral tablet
Placebo
Sponsors
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
16 Years to 24 Years
Healthy volunteers
No
Inclusion criteria
* Current frequency of at least one NSSI episode in the past 2 months * ≥ 5 past episodes of NSSI with significant tissue damage (e.g. scars present) * Psychotropic medications are dose-stable for 1 month * Ability to understand study procedures and to comply with them for the entire length of the study
Exclusion criteria
* Any MRI contraindications (e.g. metal plates, claustrophobia, braces, implanted devices) * Any current serious medical illness as defined by medical history * Current Substance Use Disorder (except Tobacco Use Disorder) * Primary psychotic disorder (e.g. schizophrenia, schizoaffective disorder, schizophreniform disorder) * Neurodevelopmental disorder such as mental retardation or autism * Changes in psychotropic medications in past 1 month * Taken NAC or glutathione on a regular basis in the past 6 months * Currently pregnant, planning to become pregnant, currently breastfeeding, or unwillingness to use contraception throughout the study. * Allergy/sensitivity to N-acetylcysteine. * Inability or unwillingness of individual or legal guardian/representative to give written informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Increase in Glutathione (GSH) Concentrations in the ACC | 28 days | increase in glutathione (GSH) concentrations in the anterior cingulate cortex (ACC) as measured by magnetic resonance spectroscopy (MRS) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in GSH Reduced-to-oxidized Ratio | 28 days | Percent increase in reduced-to-oxidized ratio of glutathione (GSH) in the blood compared to baseline |
| Change in Glutamate Concentrations | 28 days | Percent decrease in the concentrations of glutamate (GLU) in the anterior cingulate cortex (ACC) measured by MRS |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Low-Dose NAC 3600 NAC mg/day
N-acetyl cysteine: 3600 or 5400 mg/day N-acetyl cysteine | 14 |
| High-Dose NAC 5400 NAC mg/day
N-acetyl cysteine: 3600 or 5400 mg/day N-acetyl cysteine | 11 |
| Placebo Placebo
Placebo oral tablet: Placebo | 14 |
| Total | 39 |
Baseline characteristics
| Characteristic | Low-Dose NAC | High-Dose NAC | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 21 years STANDARD_DEVIATION 2 | 21 years STANDARD_DEVIATION 2 | 21 years STANDARD_DEVIATION 2 | 21 years STANDARD_DEVIATION 2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 10 Participants | 9 Participants | 11 Participants | 30 Participants |
| Sex: Female, Male Female | 14 Participants | 11 Participants | 14 Participants | 39 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 11 | 0 / 14 |
| other Total, other adverse events | 10 / 14 | 9 / 11 | 9 / 14 |
| serious Total, serious adverse events | 0 / 14 | 0 / 11 | 1 / 14 |
Outcome results
Primary
Percent Increase in Glutathione (GSH) Concentrations in the ACC
increase in glutathione (GSH) concentrations in the anterior cingulate cortex (ACC) as measured by magnetic resonance spectroscopy (MRS)
Time frame: 28 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low-Dose NAC | Percent Increase in Glutathione (GSH) Concentrations in the ACC | 5 Percent change | Standard Deviation 12 |
| High-Dose NAC | Percent Increase in Glutathione (GSH) Concentrations in the ACC | 0 Percent change | Standard Deviation 10 |
| Placebo | Percent Increase in Glutathione (GSH) Concentrations in the ACC | 2 Percent change | Standard Deviation 15 |
Secondary
Change in Glutamate Concentrations
Percent decrease in the concentrations of glutamate (GLU) in the anterior cingulate cortex (ACC) measured by MRS
Time frame: 28 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low-Dose NAC | Change in Glutamate Concentrations | -0.9 percent change | Standard Deviation 2.6 |
| High-Dose NAC | Change in Glutamate Concentrations | -1.2 percent change | Standard Deviation 4.2 |
| Placebo | Change in Glutamate Concentrations | -0.8 percent change | Standard Deviation 4.6 |
Secondary
Change in GSH Reduced-to-oxidized Ratio
Percent increase in reduced-to-oxidized ratio of glutathione (GSH) in the blood compared to baseline
Time frame: 28 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low-Dose NAC | Change in GSH Reduced-to-oxidized Ratio | 14 percent change | Standard Deviation 15 |
| High-Dose NAC | Change in GSH Reduced-to-oxidized Ratio | 28 percent change | Standard Deviation 51 |
| Placebo | Change in GSH Reduced-to-oxidized Ratio | -5 percent change | Standard Deviation 26 |