Quetiapine Treatment for Symptoms Associated With Borderline Personality Disorder
Condition: Borderline Personality Disorder
MeSH terms: Personality Disorders; Borderline Personality Disorder
Study type: Interventional
Phase: Phase 3

Summary: 
      Objective:

      The objective of this study is to quantitatively examine the efficacy of Seroquel (active
      ingredient quetiapine fumarate) in subjects with Borderline Personality Disorder (BPD). A
      secondary objective is to characterize the safety and tolerability of utilizing quetiapine in
      patients with Borderline Personality Disorder.

      Design:

      Investigator initiated, 6-week, non-placebo controlled, non-randomized, open-label, single
      drug, single-center, medication trial.

      Participants:

      Volunteers (n = 15) diagnosed with Borderline Personality Disorder using the Structured
      Clinical Interview for DSM-IV Personality Disorders (SCID-II).

      Interventions:

      Subjects with Borderline Personality Disorder are washed out of all other medications. The
      subjects are then given the study drug at a dose within the drug's known therapeutic range.
    

Detailed description: 
      Study Design: A six week, open-label, flexible dosing study using quetiapine. Subjects who
      qualify at Screening will then proceed to the baseline visit. If all inclusion and exclusion
      criteria are met, subjects will be administered quetiapine at the baseline visit. Enrollment
      will be 15 subjects. Enrollment is expected to last for a 6 month period.

      Study Flow Sheet

      Duration of Study and Visit Schedule. The subjects will have visits at the following
      intervals:

        -  Screening (Day -1 to -14)

        -  Visit 1 (Baseline)

        -  Visit 2 (Week 1)

        -  Visit 3 (Week 2)

        -  Visit 4 (Week 3)

        -  Visit 5 (Week 4)

        -  Visit 6 (Week 5)

        -  Visit 7 (Week 6)

      Screening visit (Day -1 to -14): The following procedures will be performed:

        1. Review of Inclusion and Exclusion criteria

        2. Informed consent: Subject will be enrolled after signing an IRB approved informed
           consent. A signed copy will be given to the subject.

        3. Review of Concomitant Medications

        4. Medical/Disease History & Physical Exam, Vital Signs: The subject will have a H&P
           administered by an investigator. Weight, TPR, BP will be assessed. This will be done in
           Family medicine by Dr. Robert Hudrick, DO or Dr. Andrea Woll, DO.

        5. A 12 Lead EKG will be done in Family medicine by Dr. Robert Hudrick, DO or Dr. Andrea
           Woll, DO.

        6. Diagnostic Interview and Psychological Testing: Mental status will be conducted by the
           investigator and a SCID I and SCID II psychological test will be administered for
           screening and the Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI-II),
           Buss-Durkee Hostility Inventory (BDHI), Global Assessment of Functioning (GAF), Symptom
           Checklist 90 (SCL-90-R) and the Clinical Global Impression Scale (CGI) for severity of
           illness (Global Improvement and Efficacy not rated) will be utilized to measure the
           efficacy of quetiapine in this disorder.

        7. Lab Parameters: Clinical laboratory samples will be collected and tests will be
           performed at Kennedy Health System Cherry Hill, NJ. They will be as follows:

           A. Comprehensive Metabolic Panel

             -  albumin

             -  total bilirubin

             -  calcium

             -  carbon dioxide

             -  chloride

             -  creatinine

             -  glucose

             -  alkaline phosphatase

             -  potassium

             -  total protein

             -  sodium

             -  SGOT (AST)

             -  SGPT (ALT)

             -  urea nitrogen (BUN)

           B. Urine Drug Screen

             -  amphetamines

             -  barbiturates

             -  benzo

             -  cocaine

             -  opiate

             -  PCP

             -  cannabinoids

           C. Urine HCG in women

           D. TSH

           E. CBC/Differential

           F. Electrocardiogram: EKG will screen for heart disease and arrhythmias

        8. Subjects who have abnormal laboratory results will be discontinued from the study.

      Visit 1 (Baseline).

      Review of the following:

        -  Lab work

        -  Adverse Events

        -  Concomitant Medications

        -  Inclusion and Exclusion Criteria

        -  Beck Anxiety Inventory (BAI)

        -  Beck Depression Inventory ( BDI-II)

        -  Buss-Durkee Hostility Inventory (BDHI)

        -  Global Assessment of Functioning (GAF)

        -  Symptom Checklist 90 (SCL-90-R)

        -  Clinical Global Impression Scale (CGI) for severity of illness (Global Improvement and
           Efficacy not rated)

        -  Abnormal Involuntary Movement Scale (AIMS)

        -  Simpson-Angus Scale

      Study Medication:

      The investigator completes all evaluations and determines the medication dosage.

      The study coordinator will then dispense the appropriate number of quetiapine tablets.

      Visit 2 (Week 1); Visit 3 (Week 2); Visit 4 (Week 3); Visit 5 (Week 4); Visit 6 (Week 5).

      Scales that will be used to assess positive change and medication safety during these visits
      are:

      Scales (in alphabetical order):

        -  Abnormal Involuntary Movement Scale (AIMS)

        -  Beck Anxiety Inventory

        -  Beck Depression Inventory

        -  Buss-Durkee Hostility Inventory (BDHI)

        -  Clinical Global Impression (CGI)

        -  Global Assessment of Functioning GAF

        -  Simpson-Angus Scale

      Inclusion Criteria:

      To be considered for inclusion in this study subject must:

        -  Provide written informed consent before beginning any study related activities

        -  Be between age 18 and 55 years

        -  Be able to speak, read and write English and follow simple instructions for completing
           self-rated scales

        -  Meet DSM-IV criteria for BPD as assessed by the Structured Clinical Interview for DSM-IV
           Personality Disorders (SCID-II). Those items screened positive by the subject on the
           Personality questionnaire will be further evaluated by pertinent subsections of the
           SKID-II.

      Concomitant Therapy

      Antipsychotic agents other than quetiapine will not be allowed during the study period.
      Patients who are taking other antipsychotic medication will require at least a three day
      washout period prior to the baseline visit.

      Patients on anticonvulsants, lithium and benzodiazepines will be allowed to enter the study
      if they have been on the same dose of these agents for three months prior to the baseline
      visit

      How Will the Study Be Analyzed

      Laboratory Studies: Studies will be done at baseline and will screen for liver disease,
      kidney disease, electrolyte imbalance, thyroid or parathyroid dysfunction, respiratory
      acidosis or alkalosis, anemia, adequate blood cell and platelet count, pregnancy, and
      presence of illegal drugs. Any subjects with significant laboratory abnormalities will be
      excluded from the study.

      Adverse Events: Subjects will be screened for the following side effects of quetiapine which
      are dizziness (10%), postural hypotension (7%), dry mouth (7%), and dyspepsia (6%),
      tachycardia (7%) and somnolence (18%). Patients will be also be monitored for other rare
      events including seizures, tardive dyskinesia, and neuroleptic malignant syndrome (NMS).
      Other less common side effects (> 1%) include headache (19% vs placebo 17%), asthenia (3% vs
      2%), abdominal pain (3% vs 1%), back pain (2% vs 1%), fever (2% vs 1%), constipation (9% vs
      5%),w eight gain (2% vs 0%), rash (4% vs 3%), rhinitis (3% vs 1%), and ear pain (1% vs 0%).

      Data Analysis

      The following will be reported and statistically analyzed:

        -  Number of patients who begin and complete the study (maximum n = 15).

        -  Patients who dropout of the study or are terminated with reasons.

        -  Demographic characteristics of the patients.

        -  Number of patients who had personality disorders in addition to Borderline Personality
           Disorder.

        -  The final average dose of quetiapine.

        -  The total score and percentage change of each scale and subscale utilized in the study
           and whether there was a statistically significant increase or reduction during the
           period of quetiapine administration.

        -  Movement Disorder side effects as assessed by the Abnormal Involuntary Movement Scale
           and the Simpson-Angus Scale and whether there was a statistically significant increase
           or reduction during the period of quetiapine administration.

        -  The number and percentage of adverse events that occurred during the period of
           quetiapine administration.

        -  The number and percentage of any abnormal laboratory results that occurred during the
           period of quetiapine administration.

      After completion of data collection, the data will be analyzed to determine appropriate
      parametric analyses. As the N for this study will be 15, a T-test analysis may be applicable
      if the data permit. We anticipate a preliminary demonstration of treatment effect. Individual
      weekly scores will serve as dependent variables which lend themselves to a one-way analysis
      to demonstrate difference between baseline and 6 weeks of active treatment. If our data
      permit, a two-way T-test will also be employed to demonstrate statistically significant
      differences in treatment effect. As our data will likely require the utilization of multiple
      two-way analyses, our data will be Bonferroni corrected in order to adjust for the
      possibility of false positive (type II) errors. Other parametric analyses will be employed as
      the data warrant.
    

Intervention name(s): Quetiapine Fumarate
Intervention type(s): Drug
Intervention description(s): Dosage can vary from 50 to 150 mg at PI's discretion
Other intervention name(s): Seroquel
Intervention MeSH terms: Quetiapine Fumarate
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Borderline Personality Disorder; Personality Disorder; Quetiapine; Atypical Antipsychotics; Seroquel; Antipsychotics