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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Low-Dose NAC | Experimental | 3600 NAC mg/day |
|
| High-Dose NAC | Experimental | 5400 NAC mg/day |
|
| Placebo | Placebo Comparator | Placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| N-acetyl cysteine | Drug | 3600 or 5400 mg/day N-acetyl cysteine |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Minnesota | Minneapolis | Minnesota | 55455 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34036177 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Low-Dose NAC | 3600 NAC mg/day N-acetyl cysteine: 3600 or 5400 mg/day N-acetyl cysteine |
| FG001 | High-Dose NAC | 5400 NAC mg/day N-acetyl cysteine: 3600 or 5400 mg/day N-acetyl cysteine |
| FG002 | Placebo | Placebo Placebo oral tablet: Placebo |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Low-Dose NAC | 3600 NAC mg/day N-acetyl cysteine: 3600 or 5400 mg/day N-acetyl cysteine |
| BG001 | High-Dose NAC | 5400 NAC mg/day N-acetyl cysteine: 3600 or 5400 mg/day N-acetyl cysteine |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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) | Posted | Mean | Standard Deviation | Percent change | 28 days |
|
recorded by study staff throughout the study occurring any time after informed consent is obtained for 8 weeks.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Low-Dose NAC | 3600 NAC mg/day N-acetyl cysteine: 3600 or 5400 mg/day N-acetyl cysteine |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hospitalization due to suicidality | Psychiatric disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Psychiatric | Psychiatric disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kathryn Cullen | University of Minnesota | 612-273-9732 | rega0026@umn.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 6, 2021 | Jun 12, 2023 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | May 6, 2022 | Jun 9, 2023 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D016728 | Self-Injurious Behavior |
| D003863 | Depression |
| D013405 | Suicide |
| ID | Term |
|---|---|
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
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| ID | Term |
|---|---|
| D000111 | Acetylcysteine |
| ID | Term |
|---|---|
| D003545 | Cysteine |
| D000603 | Amino Acids, Sulfur |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
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| Placebo oral tablet | Drug | Placebo |
|
| 28 days |
| BG002 | Placebo | Placebo Placebo oral tablet: Placebo |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
Placebo
Placebo oral tablet: Placebo
|
|
| Secondary | Change in GSH Reduced-to-oxidized Ratio | Percent increase in reduced-to-oxidized ratio of glutathione (GSH) in the blood compared to baseline | Posted | Mean | Standard Deviation | percent change | 28 days |
|
|
|
| Secondary | Change in Glutamate Concentrations | Percent decrease in the concentrations of glutamate (GLU) in the anterior cingulate cortex (ACC) measured by MRS | Posted | Mean | Standard Deviation | percent change | 28 days |
|
|
|
| 0 |
| 14 |
| 0 |
| 14 |
| 10 |
| 14 |
| EG001 | High-Dose NAC | 5400 NAC mg/day N-acetyl cysteine: 3600 or 5400 mg/day N-acetyl cysteine | 0 | 11 | 0 | 11 | 9 | 11 |
| EG002 | Placebo | Placebo Placebo oral tablet: Placebo | 0 | 14 | 1 | 14 | 9 | 14 |
| Gastrointestinal | Gastrointestinal disorders | Non-systematic Assessment |
|
| Cardiovascular | Cardiac disorders | Non-systematic Assessment |
|
| Nervous system | Nervous system disorders | Non-systematic Assessment |
|
| skin | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| ENT | Ear and labyrinth disorders | Non-systematic Assessment |
|
| musculoskeletal | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
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| D000596 |
| Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |