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

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

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).

Study Overview

• Status: Completed
• Conditions: Depression; Suicide; Self-Harm
• Intervention / Treatment: Drug: Placebo oral tablet; Drug: N-acetyl cysteine

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.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 20 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Minnesota

Publications and helpful links

General Publications

• Sahasrabudhe SA, Silamongkol T, Park YW, Colette A, Eberly LE, Klimes-Dougan B, Coles LD, Cloyd JC, Oz G, Mueller BA, Kartha RV, Cullen KR. Identifying Biological Signatures of N-Acetylcysteine for Non-Suicidal Self-Injury in Adolescents and Young Adults. J Psychiatr Brain Sci. 2021;6:e210007. doi: 10.20900/jpbs.20210007. Epub 2021 Apr 29.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2019
• Primary Completion (Actual): May 8, 2022
• Study Completion (Actual): October 1, 2022

Study Registration Dates

• First Submitted: June 27, 2019
• First Submitted That Met QC Criteria: June 27, 2019
• First Posted (Actual): July 2, 2019

Study Record Updates

• Last Update Posted (Actual): August 15, 2023
• Last Update Submitted That Met QC Criteria: July 24, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Suicide; Self-Injurious Behavior; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: PSYCH-2018-26890

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No