Naltrexone for Nonsuicidal Self-Injury

N/ANot Yet RecruitingNCT07641283

Seoul National University Hospital150 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Eligibility

Sex: ALLMin age: 16 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Total Number of Nonsuicidal Self-Injury Episodes During the 6-Week Treatment Period

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.

Time frame: Baseline to Week 6

Secondary Outcomes

Change From Baseline in Modified Obsessive Compulsive Drinking Scale Adapted for Nonsuicidal Self-Injury Urges Total Score

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.

Time frame: Baseline, Week 2, Week 4, and Week 6

Change From Baseline in Columbia-Suicide Severity Rating Scale Suicidal Ideation Severity Score

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.

Time frame: Baseline, Week 2, Week 4, and Week 6

Change From Baseline in Clinical Global Impressions-Severity Score

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.

Time frame: Baseline, Week 2, Week 4, and Week 6

Number of Event-Based Ecological Momentary Assessment Reports of Nonsuicidal Self-Injury Urges

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.

Time frame: During the 6-week intervention period

Number of Event-Based Ecological Momentary Assessment Reports of Nonsuicidal Self-Injury Behavior

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.

Time frame: During the 6-week intervention period

Percentage of Planned Investigational Product Doses Taken as Assessed by Pill Count

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.

Time frame: Week 2, Week 4, and Week 6

Number of Participants With Treatment-Emergent Adverse Events

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.

Time frame: Baseline through Week 6

Number of Participants With Clinically Significant Laboratory Abnormalities

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.

Time frame: Baseline and Week 6

Number of Participants With Clinically Significant Electrocardiogram Abnormalities

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.

Time frame: Baseline and Week 6

Change From Baseline in Montgomery-Åsberg Depression Rating Scale Total Score

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.

Time frame: Baseline, Week 2, Week 4, and Week 6

Change From Baseline in Hamilton Rating Scale for Anxiety Total Score

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.

Time frame: Baseline, Week 2, Week 4, and Week 6

Change From Baseline in Patient Health Questionnaire-9 Total Score

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.

Time frame: Baseline, Week 2, Week 4, and Week 6

Change From Baseline in Generalized Anxiety Disorder-7 Total Score

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.

Time frame: Baseline, Week 2, Week 4, and Week 6

Change From Baseline in Eating Disorder Examination-Questionnaire Global Score

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.

Time frame: Baseline and Week 6

Clinical Global Impressions-Improvement Score

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.

Time frame: Week 2, Week 4, and Week 6

Weekly Positive Affect Score as Assessed by the Positive and Negative Affect Schedule

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.

Time frame: Weekly during the 6-week intervention period

Weekly Negative Affect Score as Assessed by the Positive and Negative Affect Schedule

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.

Time frame: Weekly during the 6-week intervention period

Naltrexone for Nonsuicidal Self-Injury

Overview

Conditions

Interventions

Eligibility

Locations (3)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts