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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Borderline Personality Disorder, Self-Injurious Behavior

Intervention / Treatment
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* Drug: N-Acetylcysteine
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: N-Acetylcysteine<br>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<br>* 3000 mg PO (1200 mg AM, 1800 mg PM), 6 weeks<br>* Other names: NAC;|
| Placebo Comparator: placebo<br>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<br>* placebo, 2 capsules PO AM, 3 capsules PO PM, 6 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Self-Harm Inventory (SHI) Score at 6 Weeks | 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. | 6 weeks | 
| Self-Harm Inventory (SHI) Score at Baseline | 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. | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Depression Rating Scale (HAM-D) at 6 Weeks | 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. | 6 weeks | 
| Hamilton Depression Rating Scale (HAM-D) at Baseline | 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. | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Borderline Personality Disorder(BPD), Dialectical Behavioral Therapy (DBT), glutamate, N-Acetylcysteine, Borderline Personality Disorder with Self-Injurious Behavior