Signatures of N-Ac for Non-Suicidal Self-Injury in Adolescents

Study Overview
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Brief Summary
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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
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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.

Official Title
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Identifying Biological Signatures of N-Acetylcysteine for Non-Suicidal Self-Injury in Adolescents and Young Adults

Conditions
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Self-Harm, Depression, Suicide

Intervention / Treatment
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* Drug: N-acetyl cysteine
* Drug: Placebo oral tablet


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 24 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-Dose NAC<br>3600 NAC mg/day | Drug: N-acetyl cysteine<br>* 3600 or 5400 mg/day N-acetyl cysteine<br>* Other names: N-acetylcysteine;|
| Experimental: High-Dose NAC<br>5400 NAC mg/day | Drug: N-acetyl cysteine<br>* 3600 or 5400 mg/day N-acetyl cysteine<br>* Other names: N-acetylcysteine;|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo oral tablet<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in GSH Reduced-to-oxidized Ratio | Percent increase in reduced-to-oxidized ratio of glutathione (GSH) in the blood compared to baseline | 28 days | 
| Change in Glutamate Concentrations | Percent decrease in the concentrations of glutamate (GLU) in the anterior cingulate cortex (ACC) measured by MRS | 28 days |