Borderline Personality DisorderPhase 2NCT00539188
N-Acetylcysteine in Adjunct to DBT for the Treatment of Self-Injurious Behavior in BPD
A Phase 2 study testing N-Acetylcysteine in people with Borderline Personality Disorder and Self-Injurious Behavior, run by Yale University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Borderline Personality Disorder, Self-Injurious Behavior
- What is being tested?
- N-Acetylcysteine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2007to Nov 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Yale OCD Research Clinic
New Haven, Connecticut, 06519
About this study
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
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.
Read more
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.
Read the 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.
- Being tested
- N-Acetylcysteine, placebo
- Keywords
- Borderline Personality Disorder(BPD), Dialectical Behavioral Therapy (DBT), glutamate, N-Acetylcysteine, Borderline Personality Disorder with Self-Injurious Behavior
- Medical subject headings
- Borderline Personality Disorder, Self-Injurious Behavior
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-AcetylcysteineDrug
Also called NAC
3000 mg PO (1200 mg AM, 1800 mg PM), 6 weeks
placeboDrug
placebo, 2 capsules PO AM, 3 capsules PO PM, 6 weeks
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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. Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline
Secondary outcomes (2)
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.
Measured: 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.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2007 (estimated)
- Study startSep 2007
- Primary completionNov 2010
- Study completionNov 2010
Why it stopped: Study terminated due to poor subject compliance.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Borderline Personality DisorderStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Christopher J Pittenger, MD,PhD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00539188
- Sponsor's protocol ID
- 0610001908
- Status last verified
- Apr 2020
- First submitted
- 2 Oct 2007
- Last updated
- 15 Apr 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
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. doi: 10.1016/j.biopsych.2005.04.043.
PubMed 15993857Pittenger 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.
PubMed 16490414Smith BD. Self-mutilation and pharmacotherapy. Psychiatry (Edgmont). 2005 Oct;2(10):28-37.
PubMed 21120088Linehan 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.
PubMed 21963369
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00539188
- Acronym / sponsor ID
- 0610001908
- Keywords
- Borderline Personality Disorder(BPD), Dialectical Behavioral Therapy (DBT), glutamate, N-Acetylcysteine, Borderline Personality Disorder with Self-Injurious Behavior
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study terminated due to poor subject compliance.
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- Sep 2007
- Primary completion
- Nov 2010 (actual)
- Study completion
- Nov 2010 (actual)
- First posted
- 4 Oct 2007 (estimated)
- Results
- Posted 6 Mar 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| N-Acetylcysteine | Experimental | Drug: N-AcetylcysteinePatients 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 |
| placebo | Placebo comparator | Drug: placeboPatients 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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)
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N-AcetylcysteineAlso: NAC3000 mg PO (1200 mg AM, 1800 mg PM), 6 weeks | Drug | N-Acetylcysteine |
| placeboplacebo, 2 capsules PO AM, 3 capsules PO PM, 6 weeks | Drug | placebo |
Primary outcome
Self-Harm Inventory (SHI) Score at 6 Weeks
Time frame: 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.
Self-Harm Inventory (SHI) Score at Baseline
Time frame: 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.
2 secondary outcomes
Hamilton Depression Rating Scale (HAM-D) at 6 Weeks
Time frame: 6 weeks
Hamilton Depression Rating Scale (HAM-D) at Baseline
Time frame: Baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15993857Coric 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.
- Background: PubMed 16490414Pittenger 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.
- Background: PubMed 21120088Smith BD. Self-mutilation and pharmacotherapy. Psychiatry (Edgmont). 2005 Oct;2(10):28-37.
- BackgroundLinehan MM (1993). The Cognitive-Behavioral Treatment of Borderline Personality Disorder. New York: The Guilford Press.
- Background: PubMed 21963369Pittenger 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christopher J Pittenger, MD,PhD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing N-Acetylcysteine in people with Borderline Personality Disorder and Self-Injurious Behavior, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Mar 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Self-Harm Inventory (SHI) Score at 6 Weeks (time frame: 6 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00539188, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2020.