N-Acetylcysteine in Adjunct to DBT for the Treatment of Self-Injurious Behavior in BPD

This study has been terminated.
(Study terminated due to poor subject compliance.)
Sponsor:
Information provided by (Responsible Party):
Christopher Pittenger, Yale University
ClinicalTrials.gov Identifier:
NCT00539188
First received: October 2, 2007
Last updated: March 25, 2013
Last verified: March 2013
  Purpose

Self-Injurious Behavior (SIB) is a dangerous and common symptom in Borderline Personality Disorder (BPD) patients. Approximately 70% of patients with BPD engage in SIB at some point, compared to 17.5% of patients with other personality disorders. While SIB may prompt unnecessary psychiatric hospitalizations, it may also cause potential underestimation of the lethality of suicidal behavior, thus creating a major and confusing challenge in the practice of clinical psychiatry.

Dialectical Behavioral Therapy (DBT) is a collection of therapeutic techniques focused on emotional regulation, impulse control, and improving safety in patients with BPD and others with marked self-destructive behavioral tendencies. Though DBT has marked ability to reduce BPD symptomatology, including SIB, improvement in SIB is limited and dependent on extensive therapy and time.

Furthermore, the literature on the pharmacological treatment of SIB associated with BPD is scarce. Animal studies suggest that SIB may be associated with an imbalance between dopamine and glutamate in the brain. Anti-seizure medications that modulate glutamate transmission, such as lamotrigine and topiramate, have been suggested to be effective in the treatment of SIB in humans.

Preliminary evidence suggests that antiglutamatergic medications may decrease SIB in patients with BPD. Early studies have focused on the antiglutamatergic drug riluzole. More recently, we have become interested in the amino acid N-acetylcysteine (NAC), which is used clinically for its antioxidant properties and is widely available as a nutritional supplement. Recent animal studies have suggested that NAC can modulate glutamate in the central nervous system in a way very similar to that proposed for riluzole, and indeed we have observed NAC to have an effect similar to riluzole in a case of treatment-refractory obsessive-compulsive disorder.

This study will be a double-blind, randomized, and placebo-controlled evaluation of N-Acetylcysteine as an adjunct to DBT in the treatment of SIB associated with BPD. Subjects participating in this study will be recruited exclusively from the Dialectical Behavioral Therapy program of the Yale-New Haven Hospital, in order to maximize homogeneity of the psychotherapeutic care received during their participation.


Condition Intervention Phase
Borderline Personality Disorder
Self-Injurious Behavior
Drug: N-Acetylcysteine
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-Blind, Placebo-controlled Pilot Study of NAC Addition to Dialectical Behavioral Therapy for the Treatment of Self-Injurious Behavior Associated With Borderline Personality Disorder

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Self-Harm Inventory (SHI) Score at 6 Weeks [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

    The Self-Harm Inventory is assessed by asking an individual to answer (yes or no) if they have ever "intentionally, or on purpose" tried to harm themselves. The inventory contains 22 questions and a 23rd marked "other" that allows the individual to indicate a self-harm behavior not previously mentioned.

    The scoring of this instrument is determined by counting the number of endorsed self-harm behaviors out of the possible twenty-three asked. The maximum score any individual may achieve for the SHI is a 23. Any individual scoring 5 or greater is classified as suffering from BPD.

    In this study, scoring on the SHI was primarily used to assess improvement of self-harming symptoms and throughout the study by comparing participant ratings from baseline and week 6. Positive numbers indicate a decrease (i.e. participant indicated less self-harming behavior) and negative numbers indicate an increase in self-harming behaviors reported.


  • Self-Harm Inventory (SHI) Score at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]

    The Self-Harm Inventory is assessed by asking an individual to answer (yes or no) if they have ever "intentionally, or on purpose" tried to harm themselves. The inventory contains 22 questions and a 23rd marked "other" that allows the individual to indicate a self-harm behavior not previously mentioned.

    The scoring of this instrument is determined by counting the number of endorsed self-harm behaviors out of the possible twenty-three asked. The maximum score any individual may achieve for the SHI is a 23. Any individual scoring 5 or greater is classified as suffering from BPD.

    In this study, scoring on the SHI was primarily used to assess improvement of self-harming symptoms and throughout the study by comparing participant ratings from baseline and week 6. Positive numbers indicate a decrease (i.e. participant indicated less self-harming behavior) and negative numbers indicate an increase in self-harming behaviors reported.



Secondary Outcome Measures:
  • Hamilton Depression Rating Scale (HAM-D) at 6 Weeks [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

    The Hamilton Rating Scale for Depression is a multiple item questionnaire used to provide an indication of depression, and as a guide to evaluate recovery. Administered by a clinician, The questionnaire is designed for adults and is used to rate the severity of the patients depression by asking their mood, feelings of guilt, insomnia, agitation, weight change, suicidal ideation, and somatic symptoms. The scale also allows the clinician to assess the patient's level of retardation, and insight into their depression. Highest possible score is 52.

    HAM-D Scoring 0-7 = Normal 8-13 = Mild Depression 14-18 = Moderate Depression 19-22 = Severed Depression

    ≥23 = Very Severe Depression

    In this study, Baseline ratings were compared to those of week 6 to assess each participants change in depression throughout the study. A negative value indicates an increase in depression (i.e. the individual felt more depressed) and a positive value indicates a decrease in depression.


  • Hamilton Depression Rating Scale (HAM-D) at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]

    The Hamilton Rating Scale for Depression is a multiple item questionnaire used to provide an indication of depression, and as a guide to evaluate recovery. Administered by a clinician, The questionnaire is designed for adults and is used to rate the severity of the patients depression by asking their mood, feelings of guilt, insomnia, agitation, weight change, suicidal ideation, and somatic symptoms. The scale also allows the clinician to assess the patient's level of retardation, and insight into their depression. Highest possible score is 52.

    HAM-D Scoring 0-7 = Normal 8-13 = Mild Depression 14-18 = Moderate Depression 19-22 = Severed Depression

    ≥23 = Very Severe Depression

    In this study, Baseline ratings were compared to those of week 6 to assess each participants change in depression throughout the study. A negative value indicates an increase in depression (i.e. the individual felt more depressed) and a positive value indicates a decrease in depression.



Enrollment: 6
Study Start Date: September 2007
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: N-Acetylcysteine
Patients randomized to this arm will receive N-Acetylcysteine augmentation, at a standard dose (3000 mg daily), in addition to the medication regimen they are on at enrollment
Drug: N-Acetylcysteine
3000 mg PO (1200 mg AM, 1800 mg PM), 6 weeks
Other Name: NAC
Placebo Comparator: placebo
Patients randomized to this arm will receive placebo, formulated to be indistinguishable from N-Acetylcysteine, in addition to the medication regimen they are on at study enrollment.
Drug: placebo
placebo, 2 capsules PO AM, 3 capsules PO PM, 6 weeks

Detailed Description:

Investigators have withdrawn study due to poor subject compliance. After 3 consecutive participants were either unable to complete all 6 weeks of the study or dropped out of the DBT program, a decision was reached to discontinue recruitment and study was terminated.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Borderline Personality Disorder, as assessed by SCID-II
  • A score of 10 or greater on the Self Harm Inventory (SHI) at time of evaluation
  • Ability to give informed consent
  • agreement to engage in a reliable form of birth control (women only)

Exclusion Criteria:

  • primary diagnosis of a psychotic disorder
  • active substance abuse or dependence
  • unstable medical condition
  • History of intolerance/allergic reaction to N-Acetylcysteine
  • pregnancy, breastfeeding, or intent to become pregnant during study
  • Inability to understand English
  • Cognitive Impairment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00539188

Locations
United States, Connecticut
Yale OCD Research Clinic
New Haven, Connecticut, United States, 06519
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Christopher J Pittenger, MD,PhD Yale University
  More Information

Publications:
Responsible Party: Christopher Pittenger, Principal Investigator, Yale University
ClinicalTrials.gov Identifier: NCT00539188     History of Changes
Other Study ID Numbers: YOCD-3
Study First Received: October 2, 2007
Results First Received: December 21, 2012
Last Updated: March 25, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Yale University:
Borderline Personality Disorder(BPD)
Dialectical Behavioral Therapy (DBT)
glutamate
N-Acetylcysteine
Borderline Personality Disorder with Self-Injurious Behavior

Additional relevant MeSH terms:
Personality Disorders
Borderline Personality Disorder
Disease
Self-Injurious Behavior
Mental Disorders
Pathologic Processes
Behavioral Symptoms
Acetylcysteine
N-monoacetylcystine
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes

ClinicalTrials.gov processed this record on October 19, 2014