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

NCT ID: NCT00539188

Last Updated: 2020-04-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-30
• Study Completion Date: 2010-11-30

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.

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.

Conditions

Borderline Personality Disorder; Self-Injurious Behavior

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

N-Acetylcysteine

Intervention Type: DRUG

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

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.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

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

Interventions

N-Acetylcysteine

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

Intervention Type: DRUG

placebo

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

Intervention Type: DRUG

Other Intervention Names

NAC

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christopher J Pittenger, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Yale OCD Research Clinic

New Haven, Connecticut, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 15993857 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16490414 (View on PubMed)

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

Reference Type: BACKGROUND

PMID: 21120088 (View on PubMed)

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

Reference Type: 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.

Reference Type: BACKGROUND

PMID: 21963369 (View on PubMed)

Other Identifiers

0610001908

Identifier Type: -

Identifier Source: org_study_id