Naltrexone for Nonsuicidal Self-Injury

Official title

A Randomized, Double-Blinded Clinical Trial to Evaluate the Effectiveness of Naltrexone in Improving Nonsuicidal Self-Injurious Behavior

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.

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

• Drug Naltrexone 50mg (Whanin Naltrexone Tab. 50mg)
  Pure opioid antagonist administered 50mg once daily.
• Drug Placebo
  Matching placebo indistinguishable from the active drug, administered once daily.

Primary outcome measures

• Total Number of Nonsuicidal Self-Injury Episodes During the 6-Week Treatment Period [Time frame: Baseline to Week 6]

Secondary outcome measures (12)

• Change From Baseline in Modified Obsessive Compulsive Drinking Scale Adapted for Nonsuicidal Self-Injury Urges Total Score [Time frame: Baseline, Week 2, Week 4, and Week 6]
• Change From Baseline in Columbia-Suicide Severity Rating Scale Suicidal Ideation Severity Score [Time frame: Baseline, Week 2, Week 4, and Week 6]
• Change From Baseline in Clinical Global Impressions-Severity Score [Time frame: Baseline, Week 2, Week 4, and Week 6]
• Number of Event-Based Ecological Momentary Assessment Reports of Nonsuicidal Self-Injury Urges [Time frame: During the 6-week intervention period]
• Number of Event-Based Ecological Momentary Assessment Reports of Nonsuicidal Self-Injury Behavior [Time frame: During the 6-week intervention period]
• Percentage of Planned Investigational Product Doses Taken as Assessed by Pill Count [Time frame: Week 2, Week 4, and Week 6]
• Number of Participants With Treatment-Emergent Adverse Events [Time frame: Baseline through Week 6]
• Number of Participants With Clinically Significant Laboratory Abnormalities [Time frame: Baseline and Week 6]
• Number of Participants With Clinically Significant Electrocardiogram Abnormalities [Time frame: Baseline and Week 6]
• Change From Baseline in Montgomery-Åsberg Depression Rating Scale Total Score [Time frame: Baseline, Week 2, Week 4, and Week 6]
• Change From Baseline in Hamilton Rating Scale for Anxiety Total Score [Time frame: Baseline, Week 2, Week 4, and Week 6]
• Change From Baseline in Patient Health Questionnaire-9 Total Score [Time frame: Baseline, Week 2, Week 4, and Week 6]

Eligibility criteria

Inclusion criteria

• Participants must meet all of the following criteria:

• Individuals aged 16 years or older.
• Individuals with clinically significant nonsuicidal self-injurious behavior.
• 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.
• Individuals who are able to comply with study procedures, including clinical visits, medication administration, and study assessments.
• 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:

• Current serious suicidal ideation or high suicide risk, as determined by the investigator.
• Current opioid use, opioid dependence, or use of opioid-containing medications.
• Current use of opioid antagonists or medications that may interact with naltrexone, including methadone or buprenorphine.
• Use of naltrexone within 1 week before screening.
• Positive naloxone challenge test or positive urine opioid test, if applicable.
• Known hypersensitivity to naltrexone or any component of the investigational product.
• Active liver disease, active hepatitis, or clinically significant hepatic impairment.
• Clinically significant renal impairment.
• Pregnancy or breastfeeding.
• Intellectual disability, organic brain disorder, or other condition that may interfere with the participant's ability to understand study procedures or complete assessments.
• Inability to read or write Korean sufficiently to complete study assessments.
• Documented prior non-response to naltrexone for nonsuicidal self-injury, as judged by the investigator.
• Any other clinically significant medical or psychiatric condition that, in the opinion of the investigator, would make participation inappropriate or unsafe.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

South Korea · 3 centers

• Uijeongbu Eulji Medical Center — Uijeongbu-si
• Seoul National University Hospital — Seoul
• Asan medical center — Seoul

Publications

• Harris PA, Taylor R, Minor BL, Elliott V, Fernandez M, O'Neal L, McLeod L, Delacqua G, Delacqua F, Kirby J, Duda SN; REDCap Consortium. The REDCap consortium: Building an international community of software platform partners. J Biomed Inform. 2019 Jul;95:103208. doi: 10.1016/j.jbi.2019.103208. Epub 2019 May 9. PMID 31078660
• Bradburn NM, Rips LJ, Shevell SK. Answering autobiographical questions: the impact of memory and inference on surveys. Science. 1987 Apr 10;236(4798):157-61. doi: 10.1126/science.3563494. PMID 3563494
• Clark DM, Teasdale JD. Diurnal variation in clinical depression and accessibility of memories of positive and negative experiences. J Abnorm Psychol. 1982 Apr;91(2):87-95. doi: 10.1037//0021-843x.91.2.87. No abstract available. PMID 7200102
• Shiffman S, Stone AA, Hufford MR. Ecological momentary assessment. Annu Rev Clin Psychol. 2008;4:1-32. doi: 10.1146/annurev.clinpsy.3.022806.091415. PMID 18509902
• Sonne S, Rubey R, Brady K, Malcolm R, Morris T. Naltrexone treatment of self-injurious thoughts and behaviors. J Nerv Ment Dis. 1996 Mar;184(3):192-5. doi: 10.1097/00005053-199603000-00011. No abstract available. PMID 8600226
• Casner JA, Weinheimer B, Gualtieri CT. Naltrexone and self-injurious behavior: a retrospective population study. J Clin Psychopharmacol. 1996 Oct;16(5):389-94. doi: 10.1097/00004714-199610000-00008. PMID 8889912
• Buzan RD, Thomas M, Dubovsky SL, Treadway J. The use of opiate antagonists for recurrent self-injurious behavior. J Neuropsychiatry Clin Neurosci. 1995 Fall;7(4):437-44. doi: 10.1176/jnp.7.4.437. PMID 8555746
• Kars H, Broekema W, Glaudemans-van Gelderen I, Verhoeven WM, van Ree JM. Naltrexone attenuates self-injurious behavior in mentally retarded subjects. Biol Psychiatry. 1990 Apr 1;27(7):741-6. doi: 10.1016/0006-3223(90)90589-t. PMID 2158355

Identifiers

NCT: NCT07641283 · 2024-0057

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗