Nonsuicidal Self-Injury, Self-Injurious Behavior
Conditions
Keywords
Nonsuicidal self-injury, NSSI, Self-injurious behavior, Naltrexone, Opioid antagonist, Impulsivity, Suicidal ideation, Ecological momentary assessment
Brief summary
This randomized, double-blinded, placebo-controlled clinical trial aims to evaluate the efficacy and safety of naltrexone in reducing nonsuicidal self-injurious behavior among individuals with nonsuicidal self-injury. Participants will be randomly assigned to receive either naltrexone plus treatment as usual or placebo plus treatment as usual for 6 weeks. The primary objective is to determine whether naltrexone reduces the frequency of nonsuicidal self-injurious behavior compared with placebo. Secondary objectives include evaluating changes in clinical severity, suicidal ideation, self-injury-related urges, ecological momentary assessment measures, and safety outcomes.
Detailed description
Nonsuicidal self-injury is defined as the intentional destruction of one's own body tissue without suicidal intent. It is clinically important because it is associated with emotional dysregulation, impulsivity, psychiatric comorbidity, and increased risk of future suicidal behavior. However, evidence-based pharmacological treatments specifically targeting nonsuicidal self-injurious behavior remain limited. Naltrexone is an opioid receptor antagonist that has been suggested to reduce repetitive self-injurious behaviors by modulating endogenous opioid-related reinforcement mechanisms. This study will investigate whether naltrexone is effective in reducing nonsuicidal self-injurious behavior in a randomized, double-blinded, placebo-controlled design. A total of 150 participants will be enrolled across multiple study sites. Eligible participants will be randomly assigned in a 1:1 ratio to either the naltrexone group or the placebo group. The intervention period will last 6 weeks, with clinical evaluations conducted at baseline and every 2 weeks thereafter. Smartphone-based ecological momentary assessment will also be used to monitor self-injurious urges, mood states, and related behavioral variables during the study period. Safety will be assessed throughout the study through adverse event monitoring, assessment of suicidal ideation and behavior, laboratory testing, urine testing, and electrocardiography according to the study schedule.
Interventions
DRUGNaltrexone 50mg (Whanin Naltrexone Tab. 50mg)
Pure opioid antagonist administered 50mg once daily.
DRUGPlacebo
Matching placebo indistinguishable from the active drug, administered once daily.
Sponsors
Seoul National University Hospital
Asan Medical Center
Uijeongbu Eulji University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Participants and clinical outcome assessors will be blinded to treatment allocation. Randomization and investigational product assignment will be managed separately by designated unblinded personnel who are not involved in clinical outcome assessments.
Intervention model description
Participants will be randomly assigned in a 1:1 ratio to receive either naltrexone plus treatment as usual or placebo plus treatment as usual.
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must meet all of the following criteria: 1. Individuals aged 16 years or older. 2. Individuals with clinically significant nonsuicidal self-injurious behavior. 3. Individuals who are able to understand the study procedures and provide written informed consent. For minors, consent from a legal guardian and assent from the participant will be obtained according to applicable regulations. 4. Individuals who are able to comply with study procedures, including clinical visits, medication administration, and study assessments. 5. Women of childbearing potential must have a negative urine pregnancy test at screening and agree to use appropriate contraception during the study period.
Exclusion criteria
* Participants meeting any of the following criteria will be excluded: 1. Current serious suicidal ideation or high suicide risk, as determined by the investigator. 2. Current opioid use, opioid dependence, or use of opioid-containing medications. 3. Current use of opioid antagonists or medications that may interact with naltrexone, including methadone or buprenorphine. 4. Use of naltrexone within 1 week before screening. 5. Positive naloxone challenge test or positive urine opioid test, if applicable. 6. Known hypersensitivity to naltrexone or any component of the investigational product. 7. Active liver disease, active hepatitis, or clinically significant hepatic impairment. 8. Clinically significant renal impairment. 9. Pregnancy or breastfeeding. 10. Intellectual disability, organic brain disorder, or other condition that may interfere with the participant's ability to understand study procedures or complete assessments. 11. Inability to read or write Korean sufficiently to complete study assessments. 12. Documented prior non-response to naltrexone for nonsuicidal self-injury, as judged by the investigator. 13. Any other clinically significant medical or psychiatric condition that, in the opinion of the investigator, would make participation inappropriate or unsafe.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Number of Nonsuicidal Self-Injury Episodes During the 6-Week Treatment Period | Baseline to Week 6 | The total number of nonsuicidal self-injury episodes during the 6-week treatment period will be assessed by blinded clinical evaluators. A lower number indicates fewer nonsuicidal self-injury episodes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Modified Obsessive Compulsive Drinking Scale Adapted for Nonsuicidal Self-Injury Urges Total Score | Baseline, Week 2, Week 4, and Week 6 | Self-injurious urges will be assessed using the Modified Obsessive Compulsive Drinking Scale adapted for nonsuicidal self-injury urges. The total score ranges from 0 to 56, with higher scores indicating more severe self-injurious urges. |
| Change From Baseline in Columbia-Suicide Severity Rating Scale Suicidal Ideation Severity Score | Baseline, Week 2, Week 4, and Week 6 | Suicidal ideation will be assessed using the Columbia-Suicide Severity Rating Scale suicidal ideation severity score. The score ranges from 0 to 5, with higher scores indicating more severe suicidal ideation. |
| Change From Baseline in Clinical Global Impressions-Severity Score | Baseline, Week 2, Week 4, and Week 6 | Overall clinical severity will be assessed using the Clinical Global Impressions-Severity scale. The score ranges from 1 to 7, with higher scores indicating greater illness severity. |
| Number of Event-Based Ecological Momentary Assessment Reports of Nonsuicidal Self-Injury Urges | During the 6-week intervention period | Participants will complete an event-based smartphone ecological momentary assessment entry when they experience nonsuicidal self-injury urges. The outcome will be reported as the total number of event-based reports of nonsuicidal self-injury urges. A higher number indicates more frequent self-injurious urges. |
| Number of Event-Based Ecological Momentary Assessment Reports of Nonsuicidal Self-Injury Behavior | During the 6-week intervention period | Participants will complete an event-based smartphone ecological momentary assessment entry when nonsuicidal self-injury behavior occurs. The outcome will be reported as the total number of event-based reports of nonsuicidal self-injury behavior. A higher number indicates more frequent nonsuicidal self-injury behavior. |
| Percentage of Planned Investigational Product Doses Taken as Assessed by Pill Count | Week 2, Week 4, and Week 6 | Medication adherence will be assessed using pill count. Adherence will be calculated as the number of doses taken divided by the number of planned doses, multiplied by 100. The percentage ranges from 0% to 100%, with higher percentages indicating greater adherence. |
| Number of Participants With Treatment-Emergent Adverse Events | Baseline through Week 6 | Treatment-emergent adverse events will be assessed throughout the study period. The outcome will be reported as the number of participants with one or more treatment-emergent adverse events. |
| Number of Participants With Clinically Significant Laboratory Abnormalities | Baseline and Week 6 | Laboratory safety will be assessed using prespecified blood and urine tests. The outcome will be reported as the number of participants with clinically significant laboratory abnormalities as judged by the investigator. |
| Number of Participants With Clinically Significant Electrocardiogram Abnormalities | Baseline and Week 6 | Electrocardiogram safety will be assessed using standard electrocardiography. The outcome will be reported as the number of participants with clinically significant electrocardiogram abnormalities as judged by the investigator. |
| Change From Baseline in Montgomery-Åsberg Depression Rating Scale Total Score | Baseline, Week 2, Week 4, and Week 6 | Depressive symptoms will be assessed using the Montgomery-Åsberg Depression Rating Scale. The total score ranges from 0 to 60, with higher scores indicating more severe depressive symptoms. |
| Change From Baseline in Hamilton Rating Scale for Anxiety Total Score | Baseline, Week 2, Week 4, and Week 6 | Anxiety symptoms will be assessed using the Hamilton Rating Scale for Anxiety. The total score ranges from 0 to 56, with higher scores indicating more severe anxiety symptoms. |
| Change From Baseline in Patient Health Questionnaire-9 Total Score | Baseline, Week 2, Week 4, and Week 6 | Self-reported depressive symptoms will be assessed using the Patient Health Questionnaire-9. The total score ranges from 0 to 27, with higher scores indicating more severe depressive symptoms. |
| Change From Baseline in Generalized Anxiety Disorder-7 Total Score | Baseline, Week 2, Week 4, and Week 6 | Self-reported anxiety symptoms will be assessed using the Generalized Anxiety Disorder-7 scale. The total score ranges from 0 to 21, with higher scores indicating more severe anxiety symptoms. |
| Change From Baseline in Eating Disorder Examination-Questionnaire Global Score | Baseline and Week 6 | Eating disorder-related psychopathology will be assessed using the Eating Disorder Examination-Questionnaire global score. The global score ranges from 0 to 6, with higher scores indicating greater eating disorder-related psychopathology. |
| Clinical Global Impressions-Improvement Score | Week 2, Week 4, and Week 6 | Overall clinical improvement will be assessed using the Clinical Global Impressions-Improvement scale. The score ranges from 1 to 7, where 1 indicates very much improved and 7 indicates very much worse. Lower scores indicate greater improvement. |
| Weekly Positive Affect Score as Assessed by the Positive and Negative Affect Schedule | Weekly during the 6-week intervention period | Positive affect will be assessed weekly using the Positive and Negative Affect Schedule positive affect subscale through smartphone-based ecological momentary assessment. The positive affect subscale score ranges from 10 to 50, with higher scores indicating greater positive affect. |
| Weekly Negative Affect Score as Assessed by the Positive and Negative Affect Schedule | Weekly during the 6-week intervention period | Negative affect will be assessed weekly using the Positive and Negative Affect Schedule negative affect subscale through smartphone-based ecological momentary assessment. The negative affect subscale score ranges from 10 to 50, with higher scores indicating greater negative affect. |
Countries
South Korea
Contacts
CONTACTMyeong-hyeon Mun, MD, Master's Degree
Outcome results
None listed