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Efficacy of Pimozide Augmentation for Clozapine Partial Response

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00374244
Recruitment Status : Completed
First Posted : September 11, 2006
Results First Posted : March 4, 2016
Last Update Posted : March 4, 2016
Sponsor:
Collaborator:
Stanley Medical Research Institute
Information provided by (Responsible Party):
Yale University

Tracking Information
First Submitted Date  ICMJE September 7, 2006
First Posted Date  ICMJE September 11, 2006
Results First Submitted Date  ICMJE January 10, 2013
Results First Posted Date  ICMJE March 4, 2016
Last Update Posted Date March 4, 2016
Study Start Date  ICMJE January 2004
Actual Primary Completion Date June 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 4, 2016)
  • Brief Psychiatric Rating Scale (BPRS) Total Score [ Time Frame: Baseline ]
    The Brief Psychiatric Rating Scale (BPRS) is an 18-item instrument. The items are anchored on a 7-point scale (higher rating: greater severity). Total scores range from 18 to 126 (higher score: greater severity). The instrument covers areas including: somatic concerns, anxiety, emotional withdrawal, conceptual disorganization, guilt feelings, tension, mannerisms and posturing, grandiosity, depressive mood, hostility, suspiciousness, hallucinatory behavior, motor retardation, uncooperativeness, unusual thought content, blunted affect, excitement and disorientation.
  • Brief Psychiatric Rating Scale (BPRS) Total Score [ Time Frame: Endpoint (12 weeks) ]
    The Brief Psychiatric Rating Scale (BPRS) is an 18-item instrument. The items are anchored on a 7-point scale (higher rating: greater severity). Total scores range from 18 to 126 (higher score: greater severity). The instrument covers areas including: somatic concerns, anxiety, emotional withdrawal, conceptual disorganization, guilt feelings, tension, mannerisms and posturing, grandiosity, depressive mood, hostility, suspiciousness, hallucinatory behavior, motor retardation, uncooperativeness, unusual thought content, blunted affect, excitement and disorientation.
  • Scale for the Assessment of Negative Symptoms (SANS) [ Time Frame: baseline ]
    The Scale for the Assessment of Negative Symptoms (SANS) is a rating scale to measure negative symptoms in schizophrenia. The scale has 25 items (20 individual and 5 global) rated on scale of 0-5 (higher rating: greater severity). SANS is split into 5 domains, and within each domain separate symptoms are rated from 0 (absent) to 5 (severe). Domains include: Affective Flattening or Blunting, Alogia, Avolition - Apathy, Anhedonia - Asociality, Attention. The total range of the SANS is from 0 to 120.
  • Scale for the Assessment of Negative Symptoms (SANS) [ Time Frame: Endpoint (12 weeks) ]
    The Scale for the Assessment of Negative Symptoms (SANS) is a rating scale to measure negative symptoms in schizophrenia. The scale has 25 items (20 individual and 5 global) rated on scale of 0-5 (higher rating: greater severity). SANS is split into 5 domains, and within each domain separate symptoms are rated from 0 (absent) to 5 (severe). Domains include: Affective Flattening or Blunting, Alogia, Avolition - Apathy, Anhedonia - Asociality, Attention. The total range of the SANS is from 0 to 120.
Original Primary Outcome Measures  ICMJE
 (submitted: September 8, 2006)
  • Brief Psychiatric Rating Scale (BPRS)
  • Scale for the Assessment of Negative Symptoms (SANS)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 4, 2016)
  • CGI Severity of Illness Scale (CGI-S) [ Time Frame: baseline ]
    CGI Severity of Illness Scale (CGI-S) assesses severity of illness on 1-7 scale. Clinicians' experience is used to gauge the severity of illness from 'normal' (value=1) to 'among the most extremely ill patients' (value=7). The higher rating correlates with more severely ill.
  • CGI Severity of Illness Scale (CGI-S) [ Time Frame: Endpoint (12 weeks) ]
    CGI Severity of Illness Scale (CGI-S) assesses severity of illness on 1-7 scale. Clinicians' experience is used to gauge the severity of illness from 'normal' (value=1) to 'among the most extremely ill patients' (value=7). The higher rating correlates with more severely ill.
  • CGI Improvement Scale (CGI-I) [ Time Frame: Endpoint (12 weeks) ]
    CGI Improvement Scale (CGI-I) higher rating correlates with worsening of condition (vs. improvement with lower rating). The CGI-I is scored from 1 to 7 where 1 = 'very much improved' and 7 = 'very much worse'. Clinicians are asked to rate total improvement in the following manner: "...in your judgement, it is due entirely to drug treatment. Compared to his condition at admission to the project, how much has he changed?"
  • Verbal Fluency [ Time Frame: Baseline ]
    Verbal fluency was measured using the Controlled Word Association Test (COWAT). There is no range for this measure, as it is not a scale. The subjects can generate as many new words as they can, so there is no maximum. The greater the number of words one generates indicates better performance.
  • Verbal Fluency [ Time Frame: Endpoint (12 weeks) ]
    Verbal fluency was measured using the Controlled Word Association Test (COWAT). There is no range for this measure, as it is not a scale. The subjects can generate as many new words as they can, so there is no maximum. The greater the number of words one generates indicates better performance.
  • QTc [ Time Frame: Baseline ]
    The QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart. ECG machines calculate a corrected QT (QTc). QTc is the corrected QT interval in the EKG. Normal range is from 430-470ms.
  • QTc [ Time Frame: Endpoint (12 weeks) ]
    The QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart. ECG machines calculate a corrected QT (QTc). QTc is the corrected QT interval in the EKG. Normal range is from 430-470ms.
  • Processing Speed [ Time Frame: Baseline ]
    Processing speed was assessed using using Digit Symbol Coding from the Wechsler Adult Intelligence Scale, Revised (WAIS-R). The tool is used for the assessment of processing speed. The range of scores is 0 to 100- with the higher number indicating greater performance.
  • Processing Speed [ Time Frame: Endpoint (12 weeks) ]
    Processing speed was assessed using using Digit Symbol Coding from the Wechsler Adult Intelligence Scale, Revised (WAIS-R). The tool is used for the assessment of processing speed. The range of scores is 0 to 100- with the higher number indicating greater performance.
  • Verbal Learning and Memory: List A [ Time Frame: Baseline ]
    Verbal learning and memory were assessed by the Rey Auditory Verbal Learning Test (RAVLT) List A: Total Trials (1-5). This assessment consists of a list of words that the subject repeats back, it does not have an interpret-able range of scores like a traditional scale. Scores are based on number of words repeated back.
  • Verbal Learning and Memory: List A [ Time Frame: Endpoint (12 weeks) ]
    Verbal learning and memory were assessed by the Rey Auditory Verbal Learning Test (RAVLT) List A: Total Trials (1-5). This assessment consists of a list of words that the subject repeats back, it does not have an interpret-able range of scores like a traditional scale. Scores are based on number of words repeated back.
  • Verbal Learning and Memory: List B [ Time Frame: Baseline ]
    Verbal learning and memory were assessed by the Rey Auditory Verbal Learning Test (RAVLT) List B: Single Trial. This assessment consists of a list of words that the subject repeats back, it does not have an interpret-able range of scores like a traditional scale. Scores are based on number of words repeated back.
  • Verbal Learning and Memory: List B [ Time Frame: Endpoint (12 weeks) ]
    Verbal learning and memory were assessed by the Rey Auditory Verbal Learning Test (RAVLT) List B: Single Trial. This assessment consists of a list of words that the subject repeats back, it does not have an interpret-able range of scores like a traditional scale. Scores are based on number of words repeated back.
  • Trail Making Test: Trail A [ Time Frame: Baseline ]
    Working memory by Digit Span and Letter Number Sequencing, and attention/executive functions were measured by the Trail Making Test (Parts A and B). This is an assessment of attention/executive function, it does not have an interpret-able range of scores like a traditional scale. Subjects makes trails on paper against time.
  • Trail Making Test: Trail A [ Time Frame: Endpoint (12 weeks) ]
    The Trail Making Test is a neuropsychological test of visual attention and task switching. It consists of two parts in which the subject is instructed to connect a set of 25 dots as fast as possible while still maintaining accuracy. ( Arnett, James A.; Seth S. Labovitz (1995). "Effect of physical layout in performance of the Trail Making Test". Psychological Assessment 7 (2): 220-221. doi:10.1037/1040-3590.7.2.220. Retrieved 2012-02-22.) Part A is used primarily to examine cognitive processing speed. Part B, in which the subject alternates between numbers and letters, is used to examine executive functioning. (Tombaugh, T.N.T.N (2004). "Trail Making test A and B: Normative Data Stratified by Age and Education". Archives of Clinical Neuropsychology : The Official Journal of the National Academy of Neuropsychologists 19 (2): 203-214. doi:10.1016/s0887-6177(03)00039-8. Retrieved 2012-01-10.)
  • Trail Making Test: Trail B [ Time Frame: Baseline ]
    The Trail Making Test is a neuropsychological test of visual attention and task switching. It consists of two parts in which the subject is instructed to connect a set of 25 dots as fast as possible while still maintaining accuracy. ( Arnett, James A.; Seth S. Labovitz (1995). "Effect of physical layout in performance of the Trail Making Test". Psychological Assessment 7 (2): 220-221. doi:10.1037/1040-3590.7.2.220. Retrieved 2012-02-22.) Part A is used primarily to examine cognitive processing speed. Part B, in which the subject alternates between numbers and letters, is used to examine executive functioning. (Tombaugh, T.N.T.N (2004). "Trail Making test A and B: Normative Data Stratified by Age and Education". Archives of Clinical Neuropsychology : The Official Journal of the National Academy of Neuropsychologists 19 (2): 203-214. doi:10.1016/s0887-6177(03)00039-8. Retrieved 2012-01-10.)
  • Trail Making Test: Trail B [ Time Frame: Endpoint (12 weeks) ]
    The Trail Making Test is a neuropsychological test of visual attention and task switching. It consists of two parts in which the subject is instructed to connect a set of 25 dots as fast as possible while still maintaining accuracy. ( Arnett, James A.; Seth S. Labovitz (1995). "Effect of physical layout in performance of the Trail Making Test". Psychological Assessment 7 (2): 220-221. doi:10.1037/1040-3590.7.2.220. Retrieved 2012-02-22.) Part A is used primarily to examine cognitive processing speed. Part B, in which the subject alternates between numbers and letters, is used to examine executive functioning. (Tombaugh, T.N.T.N (2004). "Trail Making test A and B: Normative Data Stratified by Age and Education". Archives of Clinical Neuropsychology : The Official Journal of the National Academy of Neuropsychologists 19 (2): 203-214. doi:10.1016/s0887-6177(03)00039-8. Retrieved 2012-01-10.)
Original Secondary Outcome Measures  ICMJE
 (submitted: September 8, 2006)
  • Structured Clinical Interview for Axis I DSM-IV Disorders (SCID DSM-IV)
  • Socioeconomic status (SES)
  • Clinical Global Impression (CGI)
  • Schedule for the Deficit Syndrome
  • Straus Carpenter Levels of Function
  • Modified Barnes Akathisia Scale
  • Simpson-Angus Scale for extrapyramidal symptoms (EPS)
  • Abnormal Involuntary Movement Scale (AIMS)
  • Plasma prolactin level
  • Weight
  • Weekly occurrence form
  • Brief neurocognitive battery
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy of Pimozide Augmentation for Clozapine Partial Response
Official Title  ICMJE Efficacy of Pimozide Augmentation for Clozapine Partial Response
Brief Summary

This is a 12 week outpatient study for patients with schizophrenia who are on Clozapine, but continue to experience symptoms. The purpose of this project is to find out if small doses of pimozide (an antipsychotic medication, taken by mouth) will be helpful in reducing symptoms (such as hearing voices, having trouble in organizing your thoughts, lack of interest in life events and social activities), compared to placebo (an inactive substance, "sugar pill"), when added to clozapine in patients with schizophrenia.

The participant will be asked to come in once a week to meet with the research staff and study doctor. The participant will continue to see your regular clinician during this study for all normal appointments. The participant will remain on your current medications throughout the study. During the study you will be randomly selected to be put on a small dose of Pimozide or placebo.

Detailed Description

If you choose to participate, you will first have screening tests to find out if you are eligible. The study physician will do a number of tests including a physical examination, a routine medical history, lab tests for blood and urine, and EKG (to monitor your heart) and interviews about your physical and mental health.

At each visit you will complete an EKG (to monitor your heart), vital signs, and discuss how you are feeling with the research staff and doctor. Once a month, we will also conduct a slightly longer interview with you about your symptoms and draw one tube of blood to check your Clozapine level. At the beginning and end of the study, you will do some pencil and paper games called "Neurocognitive tests".

If you are interested in participating in this study, we will go over it in greater detail with you, including the possible benefits and risks associated with participating. We will make sure you understand the study before you begin. This study is completely voluntary, which means that you can choose to stop participating in the study at any time.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Schizophrenia
Intervention  ICMJE
  • Drug: Pimozide
    half of the subjects are randomized to the active drug group
  • Drug: placebo
    half of the subjects are randomized to placebo group
Study Arms  ICMJE
  • Placebo Comparator: 1
    placebo pimozide
    Intervention: Drug: placebo
  • Active Comparator: 2
    active pimozide
    Intervention: Drug: Pimozide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 4, 2016)
28
Original Enrollment  ICMJE
 (submitted: September 8, 2006)
60
Actual Study Completion Date  ICMJE June 2011
Actual Primary Completion Date June 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of schizophrenia or schizoaffective disorder.
  • A minimum Brief Psychiatric Rating Scale (BPRS) score of 35 and a BPRS psychotic symptom cluster score of at least 8.
  • Currently taking clozapine with a blood level between 350-1000 ng/ml and on a stable dose of clozapine for the past 2 weeks.
  • Able to give informed consent.

Exclusion Criteria:

  • A history of significant medical/neurological disease such as thyroid, renal, hepatic abnormality, seizure disorder.
  • History of Neuroleptic Malignant Syndrome.
  • Current substance abuse determined by urine toxicology.
  • Cardiac arrhythmia, sinus bradycardia (heart rate less than 60/min), sinus tachycardia (heart rate greater than 110/min), supraventricular tachycardia, ventricular tachycardia, Wolff-Parkinson-White Syndrome, first, second, third degree atrioventricular (AV) block, atrial fibrillation, atrial flutter and junctional complexes. in baseline electrocardiogram (EKG). Study doctors will examine the EKGs and consult with an internist/cardiologist as needed.
  • on EKG: QTc > 450 ms.
  • Current use of macrolide antibiotics (e.g., erythromycin, clarithromycin), azole antifungal agents (e.g., ketoconazole, itraconazole), protease inhibitors (e.g., ritonavir, indinavir), nefazodone, and other medications that are associated with prolonged QTc.
  • Current use of antipsychotics other than clozapine.
  • Current use of sertraline.
  • IQ level below 70.
  • At high risk for suicidal/homicidal behavior.
  • Pregnancy, lack of birth control for females of childbearing age (female patients must report use of effective method for birth control such as birth control pills, condoms, barrier methods, abstinence or have written statement from their doctors that they are medically sterile).
  • Non-English speaking.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00374244
Other Study ID Numbers  ICMJE 02T-251
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Yale University
Study Sponsor  ICMJE Yale University
Collaborators  ICMJE Stanley Medical Research Institute
Investigators  ICMJE
Principal Investigator: Handan Gunduz-Bruce, MD Yale University School of Medicine, Dept of Psychiatry
PRS Account Yale University
Verification Date February 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP