Clinical Trial: Early Study of N-Acetylcysteine to Treat Deliberate Self-Harm in Adolescents

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: N-Acetylcysteine in the Treatment of Deliberate Self-Harm in Adolescents: An Open Label Pilot Study

Brief Summary:

Deliberate Self-Harm (DSH) among adolescents is a serious behavioral problem associated with significant injury, impaired functioning, reduced quality of life, and high rates of psychiatric hospitalizations. While DSH has not been shown to have a direct link to suicide attempts themselves, there is a clear link between individuals who engage in DSH and overall rates of suicide. There is currently no medication treatment approved by the FDA for the treatment of DSH.

The goal of this study is to evaluate the efficacy and safety of the dietary supplement N-Acetylcysteine in adolescents aged 13-21 with deliberate self-harm behaviors. There will be an additional neuroimaging component to expand knowledge regarding the neural correlates of this treatment in the study population. We hypothesize that N-Acetylcysteine will reduce the severity of deliberate self harm behaviors because this supplement has been helpful in treating disorders that share some similar traits with DSH. We will be using this medication in 40 young people who deliberately harm themselves and we will assess the severity of their behaviors while being treated with this dietary supplement. We also will collect neuroimaging data on the study participants at baseline and after the treatment with N-Acetylcysteine and compare it to 40 age-matched healthy peer neuroimaging data. The purpose of including this healthy group is to expand knowledge about neural correlates of the study population prior to treatment.

Detailed Summary:

Deliberate Self-Harm (DSH) among adolescents is a serious behavioral problem associated with significant morbidity and mortality, impaired functioning, reduced quality of life, and high rates of psychiatric hospitalizations. Rates of DSH among high-school adolescents range between 14% and 21%, highlighting the need for effective behavioral and pharmacological interventions . Because DSH has been closely linked to Borderline Personality Disorder (BPD), treatments that have been used successfully for BPD such as Dialectical Behavior Therapy (DBT) have been used to treat adolescents with DSH. While DSH has not been shown to have a direct link to suicide attempts themselves, there is a clear link between individuals who engage in DSH and overall rates of suicide. In addition to these high rates of DSH in adolescents, research is continuing to show that similar to adult patients; adolescent DSH is related to high levels of impulsivity.

Considerable advances in the understanding of the neurobiology of risk and reward and impulsivity have improved the general understanding of the neuropathology of a behavior such as DSH. Our previous neuroimaging research of DSH in BPD found that frontal white matter integrity was significantly impaired in these individuals. One conceptualization of DSH is that it represents an imbalance between a strong desire for the reward of DSH (i.e. an overactive ventral tegmental area [VTA]) and an inability to inhibit the drive (i.e. impaired inferior frontal cortex). If the frontal cortex is impaired due to inadequate white matter integrity as our earlier study demonstrated, then reducing the drive for DSH may be the most beneficial target for treatment. Glutamate is known to activate dopamine neurons in the VTA. Because such activation can increase dopamine release in mesocorticolimbic targets, this glutamate-dopamine interaction in the VTA may underli
Sponsor: University of Minnesota - Clinical and Translational Science Institute

Current Primary Outcome:

• Deliberate Self Harm Inventory Clinical Change Version (DSHI-CCV) [ Time Frame: Every 2 weeks ]
  Assesses frequency and type of deliberate self harm.
• K-SADS-PL [ Time Frame: Intake ]
  A semi-structured clinical interview conducted separately with child and parent. Clinicians formulate the diagnosis during a consensus meeting, combining all clinical information.
• Inventory of Statements about Self-Injury (ISAS) [ Time Frame: Every 2 weeks ]
  Questionnaire regarding self injurious behavior.

Original Primary Outcome: Deliberate Self Harm Inventory Clinical Change Version [ Time Frame: Every 2 weeks ]

Current Secondary Outcome:

• Columbia Suicide Severity Rating Scale (CSSRS) [ Time Frame: Every 2 weeks ]
  Measure of suicide risk to assess safety during the study.
• Barrett Impulsivity Scale (BIS) [ Time Frame: Intake, Exit ]
  This instrument will assess the effect of the intervention on impulsivity factors.
• Deliberate Self-Harm Questionnaire-Mood (DSHQ-M) [ Time Frame: Intake ]
  Questionnaire regarding mood before, after, and during engaging in self-injurious behavior.
• BDI-II [ Time Frame: Intake, Baseline MRI, Exit MRI ]
  Assesses depressive mood in last two weeks.
• Iowa Gambling Task (IGT) [ Time Frame: Intake, Exit ]
  Game used to measure reward processing
• Symptom Check-List 90 (SCL-90) [ Time Frame: Intake, Exit ]
  Looks at correlation between amygdala-thalamus connectivity and interpersonal sensitivity.
• Difficulties in Emotion Regulation Scale (DERS) [ Time Frame: Intake, Exit ]
  Used to assess capacity for emotion regulation.
• Children's Depression Rating Scale - Revised (CDRS-R) [ Time Frame: Intake ]
  A questionnaire that will help assess participant's depression
• NIH Toolbox [ Time Frame: Intake ]
  The NIH tool box is compromised of 2 computer-based measures: the Flanker Task, and the Dimensional Card Sort Test. The participant will complete both measures. These will measure neurocognitive functioning
• Wechsler Abbreviated Scale of Intelligence (WASI-2) [ Time Frame: Intake ]
  Used to assess IQ
• Tanner Questionnaire [ Time Frame: Intake ]
  This questionnaire will be used to assess pubertal stages of participants
• Personality Assessment Inventory (PAI) [ Time Frame: Intake ]
  A multi-scale test of psychological functioning that assesses constructs relevant to personality and psychopathology evaluation.
• Satisfaction with Life Scale [ Time Frame: Intake, Exit ]
  This questionnaire looks at the participants satisfaction with their life at the moment
• Toronto Alexithymia Scale (TAS) [ Time Frame: Intake, Exit ]
  Will assess the presence or extent to which the participant exhibits Alexithymia.
• Rejection Sensitivity Questionnaire - Adolescent (RSQ-A) [ Time Frame: Intake ]
  Assesses the extent to which the participant perceives rejection in their daily lives.
• Self-Injury Assessment Scale (SIAS) [ Time Frame: Every 2 weeks ]
  Provides more information about the participant's self-harm behaviors over the past two weeks.

Original Secondary Outcome:

• Columbia Suicide Severity Rating Scale [ Time Frame: Every 2 weeks ]
  Measure of suicide risk to assess safety during the study.
• Self Injury Assessment Scale [ Time Frame: Every 2 weeks ]
  This is a seperate instrument to measure self harm.
• Barrett Impulsivity Scale [ Time Frame: Every 2 weeks ]
  This instrument will assess the effect of the intervention on impulsivity factors.

Information By: University of Minnesota - Clinical and Translational Science Institute

Dates:
Date Received: April 26, 2010
Date Started: March 2011
Date Completion:
Last Updated: June 9, 2015
Last Verified: June 2015