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

• Sponsor: Yale University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00539188
• Collaborator: (none)
• Enrollment: 6
• Location: 1
• Arms: 2
• Duration (Months): 38
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Borderline Personality Disorder; Self-Injurious Behavior	Drug: N-Acetylcysteine; Drug: placebo	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, 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
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Nov 1, 2010
• Actual Study Completion Date: Nov 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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

Outcome Measures

Primary Outcome Measures

1. Self-Harm Inventory (SHI) Score at 6 Weeks [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.

2. Self-Harm Inventory (SHI) Score at Baseline [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.

Secondary Outcome Measures

1. Hamilton Depression Rating Scale (HAM-D) at 6 Weeks [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.

2. Hamilton Depression Rating Scale (HAM-D) at Baseline [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• Linehan MM (1993). The Cognitive-Behavioral Treatment of Borderline Personality Disorder. New York: The Guilford Press.
• 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. Review.
• 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. Review.
• Smith BD. Self-mutilation and pharmacotherapy. Psychiatry (Edgmont). 2005 Oct;2(10):28-37.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT00539188
• Other Study ID Numbers: 0610001908
• First Posted: Oct 4, 2007
• Last Update Posted: Apr 15, 2020
• Last Verified: Apr 1, 2020

• 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; Self-Injurious Behavior; Acetylcysteine; N-monoacetylcystine

Study Results

Participant Flow

Arm/Group Title	N-Acetylcysteine	Placebo
Arm/Group Description	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 N-Acetylcysteine : 3000 mg PO (1200 mg AM, 1800 mg PM), 6 weeks	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. placebo : placebo, 2 capsules PO AM, 3 capsules PO PM, 6 weeks
Period Title: Overall Study
STARTED	4	2
Received Allocated Intervention	3	2
COMPLETED	1	1
NOT COMPLETED	3	1

Baseline Characteristics

Arm/Group Title	N-Acetylcysteine	Placebo	Total
Arm/Group Description	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 N-Acetylcysteine : 3000 mg PO (1200 mg AM, 1800 mg PM), 6 weeks	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. placebo : placebo, 2 capsules PO AM, 3 capsules PO PM, 6 weeks	Total of all reporting groups
Overall Participants	4	2	6
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	4 100%	2 100%	6 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	3 75%	1 50%	4 66.7%
Male	1 25%	1 50%	2 33.3%

Outcome Measures

1. Primary Outcome

Title	Self-Harm Inventory (SHI) Score at 6 Weeks
Description	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.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	N-Acetylcysteine	Placebo
Arm/Group Description	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 N-Acetylcysteine : 3000 mg PO (1200 mg AM, 1800 mg PM), 6 weeks	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. placebo : placebo, 2 capsules PO AM, 3 capsules PO PM, 6 weeks
Measure Participants	1	1
Number [units on a scale]	5	1

2. Secondary Outcome

Title	Hamilton Depression Rating Scale (HAM-D) at 6 Weeks
Description	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.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	N-Acetylcysteine	Placebo
Arm/Group Description	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 N-Acetylcysteine : 3000 mg PO (1200 mg AM, 1800 mg PM), 6 weeks	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. placebo : placebo, 2 capsules PO AM, 3 capsules PO PM, 6 weeks
Measure Participants	1	1
Number [units on a scale]	28	18

3. Primary Outcome

Title	Self-Harm Inventory (SHI) Score at Baseline
Description	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.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	N-Acetylcysteine	Placebo
Arm/Group Description	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 N-Acetylcysteine : 3000 mg PO (1200 mg AM, 1800 mg PM), 6 weeks	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. placebo : placebo, 2 capsules PO AM, 3 capsules PO PM, 6 weeks
Measure Participants	1	1
Number [units on a scale]	8	4

4. Secondary Outcome

Title	Hamilton Depression Rating Scale (HAM-D) at Baseline
Description	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.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	N-Acetylcysteine	Placebo
Arm/Group Description	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 N-Acetylcysteine : 3000 mg PO (1200 mg AM, 1800 mg PM), 6 weeks	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. placebo : placebo, 2 capsules PO AM, 3 capsules PO PM, 6 weeks
Measure Participants	1	1
Number [units on a scale]	25	27

Adverse Events

Arm/Group Title	N-Acetylcysteine		Placebo
Arm/Group Description	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 N-Acetylcysteine : 3000 mg PO (1200 mg AM, 1800 mg PM), 6 weeks		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. placebo : placebo, 2 capsules PO AM, 3 capsules PO PM, 6 weeks
All Cause Mortality
	N-Acetylcysteine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	N-Acetylcysteine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	N-Acetylcysteine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/2 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.