A Novel Drug for Borderline Personality Disorder

Study Overview
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Brief Summary
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Borderline Personality Disorder (BPD) is one of the most prevalent psychiatric disorders with high morbidity and mortality. It affects the lives of millions worldwide and is often highly incapacitating, leading to significant psychosocial dysfunction. Moreover, nearly all patients have experienced suicidal ideation and about 10% actually commit suicide, a rate almost 50 times higher than in the general population. Mostly young women are at greater risk for the disorder and are three times more likely to be diagnosed with BPD than men. BPD aetiology is complex and could be explained by both biological and environmental factors. Among the environmental factors, sexual or physical abuse, parental divorce, loss or illnesses are identified as the most common ones. These factors can induce dysfunctional behaviours, which might cause emotional dysregulation, high impulsivity and frequent self- injurious behaviour. However, there are no pharmacologic interventions that are known to be specifically effective to treat BPD. Therapeutic options for this devastating disorder is still far from adequate for treating acute illness episodes, relapses, and recurrences and in restoring premorbid functioning. In addition, some patients are unable to tolerate existing therapies for BPD, which leads to either frequent changes in medications or to non-adherence. Therefore there is an urgent need for the development of more rapidly effective treatments for BPD. A growing body of evidence suggests that glutamatergic neurotransmission, in particular N-methyl-D-aspartate (NMDA) subtype may play a role in the pathophysiology of multiple psychiatric disorders. This has led to various clinical trials with glutamate modulating drugs. The trial drug is an uncompetitive NMDA receptor antagonist approved for Alzheimer's disease is increasingly being studied in a variety of non-dementia psychiatric disorders. Results from these studies have proved that the trial drug was safe and well tolerated and has the potential for use in the treatment of psychiatric disorders. To date, there are no published data on the use of trial drug in the treatment for BPD. Therefore, the investigators intend to study the efficacy of this novel drug as an addition to ongoing therapy with atypical antipsychotics in patients with Borderline Personality Disorder. This study will recruit 150 BPD patients. The patients will be randomly allocated to receive either the study medication (20mg/ day) or placebo via oral administration for twelve weeks. To observe the efficacy of the trial treatment, all participants will be assessed at various time intervals for different borderline and cognitive symptoms.

Official Title
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A Randomised Double-blind Placebo Controlled Investigation of the Efficacy of a Novel Drug as an Adjunct in Patients With Borderline Personality Disorder

Conditions
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Borderline Personality Disorder

Intervention / Treatment
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* Drug: NMDA receptor antagonist (active drug)
* Other: Lactose packed capsule (inert/inactive arm)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Participants will be eligible to proceed in the study if they meet all of the following criteria (as determined in the screening session): Men and women aged between 18-65 years of age A diagnosis of BPD according to the Diagnostic Interview for Borderline patients or the Zanarini Rating Scale for Borderline Personality Disorder Proficient in reading and writing English Exclusion criteria Potential participants who meet the criteria for any of the following will be excluded from participating in the study: Clinical evidence of CNS pathology, neurological disorder, head injury, epileptic seizures or convulsions. Currently pregnant or breastfeeding A current DSM-IV-TR diagnosis of substance abuse or dependence disorder, or another Axis I disorder including a past or current diagnosis of schizophrenia, delusional (paranoid) disorder, schizoaffective disorder, bipolar I (mixed, manic, depressed or euthymic) or psychotic depression. Individuals with bipolar II will be included Clinically significant and active evidence of liver or kidney disease, hematological, respiratory, endocrine or cardiovascular disease. Use of prescription drugs that may cause relevant drug interactions with the study drug according to the summary of product characteristics: NMDAR antagonists (amantadine, ketamine, dextromethorphan), L-Dopa, dopamine agonists and cholinergic agonists. Commencing new psychotherapy/ new medication during the trial period. History of mental retardation or documented IQ below 75

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: NMDA receptor antagonist<br>20mg/daily for 12 weeks (84 days) | Drug: NMDA receptor antagonist (active drug)<br> <br> |
| Placebo Comparator: Placebo tablet<br>1 capsule/daily for 12 weeks (84 days) | Other: Lactose packed capsule (inert/inactive arm)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Zanarini Rating Scale for Borderline Personality Disorder | The Zanarini Rating Scale is a nine-item, validated, clinician-based diagnostic interview. It assesses the severity of DSM-IV-based Borderline personality disorder symptoms. This scale also measures meaningful changes in symptoms over time. | Weeks 0, 2, 4, 6, 8, 10, 12 | 
| Borderline Evaluation of Severity over Time (BEST) | The Borderline Evaluation of Severity over Time (BEST) is a 15-item self-report measure that allows patients with borderline personality disorder (BPD) to rate the degree of impairment or interference from each of the nine BPD criteria over the past two weeks. Each time is rated on a 5-point scale, and scores can range from 12 to 72. Subscales include negative thoughts and feelings, positive behaviours and negative behaviours. The BEST is used to assess the severity of and change in borderline symptoms over the course of treatment. | Weeks 0,2,4,6,8,10,12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cogstate (cognitive assessment) | Cogstate tests have been designed, developed and validated to both identify and measure cognitive impairment, and to track or monitor cognitive change. The tasks use novel visual and verbal stimuli to ensure assessment is culture-neutral and not limited by a participant's level of education. | Baseline and Week 12 | 
| BPDSI | Borderline Personality Disorder Severity Index-IV (BPDSI-IV) | Baseline and Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Boderline Personality Disorder, Mental Illness, Cognition