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

NCT00539188 | Terminated Phase 2 Results

• 1 other identifier: 0610001908
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Borderline Personality Disorder; Self-Injurious Behavior

Keywords

Borderline Personality Disorder(BPD); Dialectical Behavioral Therapy (DBT); glutamate; N-Acetylcysteine; Borderline Personality Disorder with Self-Injurious Behavior

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Hamilton Depression Rating Scale (HAM-D) at 6 Weeks

  6 weeks

• Hamilton Depression Rating Scale (HAM-D) at Baseline

  Baseline

Study Arms (2)

N-Acetylcysteine

EXPERIMENTAL

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

placebo

PLACEBO COMPARATOR

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

Interventions

N-Acetylcysteine DRUG

3000 mg PO (1200 mg AM, 1800 mg PM), 6 weeks

Also known as: NAC

N-Acetylcysteine

placebo DRUG

placebo, 2 capsules PO AM, 3 capsules PO PM, 6 weeks

placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

Yale OCD Research Clinic

New Haven, Connecticut, 06519, United States

Location

Related Publications (5)

• Coric V, Taskiran S, Pittenger C, Wasylink S, Mathalon DH, Valentine G, Saksa J, Wu YT, Gueorguieva R, Sanacora G, Malison RT, Krystal JH. Riluzole augmentation in treatment-resistant obsessive-compulsive disorder: an open-label trial. Biol Psychiatry. 2005 Sep 1;58(5):424-8. doi: 10.1016/j.biopsych.2005.04.043.

  PMID: 15993857 BACKGROUND

• Pittenger C, Krystal JH, Coric V. Glutamate-modulating drugs as novel pharmacotherapeutic agents in the treatment of obsessive-compulsive disorder. NeuroRx. 2006 Jan;3(1):69-81. doi: 10.1016/j.nurx.2005.12.006.

  PMID: 16490414 BACKGROUND

• Smith BD. Self-mutilation and pharmacotherapy. Psychiatry (Edgmont). 2005 Oct;2(10):28-37.

  PMID: 21120088 BACKGROUND

• Linehan MM (1993). The Cognitive-Behavioral Treatment of Borderline Personality Disorder. New York: The Guilford Press.

  BACKGROUND

• Pittenger C, Bloch MH, Williams K. Glutamate abnormalities in obsessive compulsive disorder: neurobiology, pathophysiology, and treatment. Pharmacol Ther. 2011 Dec;132(3):314-32. doi: 10.1016/j.pharmthera.2011.09.006. Epub 2011 Sep 22.

  PMID: 21963369 BACKGROUND

MeSH Terms

Conditions

Borderline Personality Disorder; Self-Injurious Behavior

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Personality Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Christopher Pittenger, MD Ph.D
• Organization: Yale University School of Medicine

christopher.pittenger@yale.edu

203-974-7675

Study Officials

• Christopher J Pittenger, MD,PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2007
• First Posted: October 4, 2007
• Study Start: September 1, 2007
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2010
• Last Updated: April 15, 2020
• Results First Posted: March 6, 2013

Record last verified: 2020-04

Locations

US (1)