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Efficacy of Pimozide Augmentation for Clozapine Partial Response

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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

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Schizophrenia
Interventions Drug: Pimozide
Drug: placebo
Enrollment 28
Recruitment Details This clinical trial was conducted at the outpatient clinics of the West Haven VA, Connecticut Mental Health Center of Yale Department of Psychiatry, and the Zucker-Hillside Hospital of Long Island Jewish Health Care System, and approved by the respective Institutional Review Boards.
Pre-assignment Details Prior to randomization, a stable dose of clozapine for the past 2 weeks with a blood level of at least 350 ng/ml was targeted. Subjects were stratified as to whether they were receiving psychoactive medications such as mood stabilizers, to ensure that about equal numbers of subjects were randomized based on this treatment profile.
Arm/Group Title Placebo Pimozide Active Pimozide
Hide Arm/Group Description Half of the subjects were randomized to placebo group. Half of the subjects are randomized to the active drug.
Period Title: Overall Study
Started 14 14
Completed 14 14
Not Completed 0 0
Arm/Group Title Placebo Pimozide Active Pimozide Total
Hide Arm/Group Description Half of the subjects were randomized to placebo group. Half of the subjects are randomized to the active drug. Total of all reporting groups
Overall Number of Baseline Participants 14 14 28
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 14 participants 14 participants 28 participants
41.5  (2.8) 44.3  (2.0) 43.0  (9.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 14 participants 28 participants
Female
4
  28.6%
4
  28.6%
8
  28.6%
Male
10
  71.4%
10
  71.4%
20
  71.4%
1.Primary Outcome
Title Brief Psychiatric Rating Scale (BPRS) Total Score
Hide Description 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.
Time Frame Baseline
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Subjects were analyzed intent to treat.
Arm/Group Title Placebo Pimozide Active Pimozide
Hide Arm/Group Description:
Half of the subjects were randomized to placebo group.
Half of the subjects are randomized to the active drug.
Overall Number of Participants Analyzed 14 14
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
44.1  (2.0) 44.3  (2.0)
2.Primary Outcome
Title Brief Psychiatric Rating Scale (BPRS) Total Score
Hide Description 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.
Time Frame Endpoint (12 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Subjects were analyzed intent to treat.
Arm/Group Title Placebo Pimozide Active Pimozide
Hide Arm/Group Description:
Half of the subjects were randomized to placebo group.
Half of the subjects are randomized to the active drug.
Overall Number of Participants Analyzed 14 14
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
37.9  (2.1) 39.6  (2.1)
3.Primary Outcome
Title Scale for the Assessment of Negative Symptoms (SANS)
Hide Description 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.
Time Frame baseline
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analyzed intent to treat.
Arm/Group Title Placebo Pimozide Active Pimozide
Hide Arm/Group Description:
Half of the subjects were randomized to placebo group.
Half of the subjects are randomized to the active drug.
Overall Number of Participants Analyzed 14 14
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
44.3  (5.9) 38.5  (5.8)
4.Primary Outcome
Title Scale for the Assessment of Negative Symptoms (SANS)
Hide Description 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.
Time Frame Endpoint (12 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analyzed intent to treat.
Arm/Group Title Placebo Pimozide Active Pimozide
Hide Arm/Group Description:
Half of the subjects were randomized to placebo group.
Half of the subjects are randomized to the active drug.
Overall Number of Participants Analyzed 14 14
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
36.3  (5.9) 37.3  (5.9)
5.Secondary Outcome
Title CGI Severity of Illness Scale (CGI‐S)
Hide Description 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.
Time Frame baseline
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analyzes intent to treat.
Arm/Group Title Placebo Pimozide Active Pimozide
Hide Arm/Group Description:
Half of the subjects were randomized to placebo group.
Half of the subjects are randomized to the active drug.
Overall Number of Participants Analyzed 14 14
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
4.1  (0.5) 4.0  (0.9)
6.Secondary Outcome
Title CGI Severity of Illness Scale (CGI‐S)
Hide Description 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.
Time Frame Endpoint (12 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analyzed intent to treat.
Arm/Group Title Placebo Pimozide Active Pimozide
Hide Arm/Group Description:
Half of the subjects were randomized to placebo group.
Half of the subjects are randomized to the active drug.
Overall Number of Participants Analyzed 14 14
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
3.9  (0.8) 3.9  (0.5)
7.Secondary Outcome
Title CGI Improvement Scale (CGI‐I)
Hide Description 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?"
Time Frame Endpoint (12 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analyzed intent to treat.
Arm/Group Title Placebo Pimozide Active Pimozide
Hide Arm/Group Description:
Half of the subjects were randomized to placebo group.
Half of the subjects are randomized to the active drug.
Overall Number of Participants Analyzed 14 14
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
2.8  (1.0) 3.4  (0.5)
8.Secondary Outcome
Title Verbal Fluency
Hide Description 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.
Time Frame Baseline
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat Analysis
Arm/Group Title Placebo Pimozide Active Pimozide
Hide Arm/Group Description:
Half of the subjects were randomized to placebo group.
Half of the subjects are randomized to the active drug.
Overall Number of Participants Analyzed 14 14
Mean (Standard Deviation)
Unit of Measure: words
12.2  (1.4) 10.5  (1.5)
9.Secondary Outcome
Title Verbal Fluency
Hide Description 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.
Time Frame Endpoint (12 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat Analysis
Arm/Group Title Placebo Pimozide Active Pimozide
Hide Arm/Group Description:
Half of the subjects were randomized to placebo group.
Half of the subjects are randomized to the active drug.
Overall Number of Participants Analyzed 14 14
Mean (Standard Deviation)
Unit of Measure: words
12.3  (1.5) 11.1  (1.5)
10.Secondary Outcome
Title QTc
Hide Description 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.
Time Frame Baseline
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intention to Treat
Arm/Group Title Placebo Pimozide Active Pimozide
Hide Arm/Group Description:
Half of the subjects were randomized to placebo group.
Half of the subjects are randomized to the active drug.
Overall Number of Participants Analyzed 14 14
Mean (Standard Deviation)
Unit of Measure: ms
408.8  (5.0) 412.3  (5.1)
11.Secondary Outcome
Title QTc
Hide Description 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.
Time Frame Endpoint (12 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intention to Treat
Arm/Group Title Placebo Pimozide Active Pimozide
Hide Arm/Group Description:
Half of the subjects were randomized to placebo group.
Half of the subjects are randomized to the active drug.
Overall Number of Participants Analyzed 14 14
Mean (Standard Deviation)
Unit of Measure: ms
412.9  (5.0) 420.3  (5.2)
12.Secondary Outcome
Title Processing Speed
Hide Description 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.
Time Frame Baseline
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat Analysis
Arm/Group Title Placebo Pimozide Active Pimozide
Hide Arm/Group Description:
Half of the subjects were randomized to placebo group.
Half of the subjects are randomized to the active drug.
Overall Number of Participants Analyzed 14 14
Mean (Standard Deviation)
Unit of Measure: units on a scale
48.8  (4.6) 43.3  (4.9)
13.Secondary Outcome
Title Processing Speed
Hide Description 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.
Time Frame Endpoint (12 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat Analysis
Arm/Group Title Placebo Pimozide Active Pimozide
Hide Arm/Group Description:
Half of the subjects were randomized to placebo group.
Half of the subjects are randomized to the active drug.
Overall Number of Participants Analyzed 14 14
Mean (Standard Deviation)
Unit of Measure: units on a scale
46.5  (4.7) 42.8  (5.0)
14.Secondary Outcome
Title Verbal Learning and Memory: List A
Hide Description 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.
Time Frame Baseline
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat Analysis
Arm/Group Title Placebo Pimozide Active Pimozide
Hide Arm/Group Description:
Half of the subjects were randomized to placebo group.
Half of the subjects are randomized to the active drug.
Overall Number of Participants Analyzed 14 14
Mean (Standard Deviation)
Unit of Measure: words
40.0  (3.3) 26.5  (2.8)
15.Secondary Outcome
Title Verbal Learning and Memory: List A
Hide Description 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.
Time Frame Endpoint (12 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat Analysis
Arm/Group Title Placebo Pimozide Active Pimozide
Hide Arm/Group Description:
Half of the subjects were randomized to placebo group.
Half of the subjects are randomized to the active drug.
Overall Number of Participants Analyzed 14 14
Mean (Standard Deviation)
Unit of Measure: words
38.0  (4.8) 32.3  (4.2)
16.Secondary Outcome
Title Verbal Learning and Memory: List B
Hide Description 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.
Time Frame Baseline
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat Analysis
Arm/Group Title Placebo Pimozide Active Pimozide
Hide Arm/Group Description:
Half of the subjects were randomized to placebo group.
Half of the subjects are randomized to the active drug.
Overall Number of Participants Analyzed 14 14
Mean (Standard Deviation)
Unit of Measure: words
3.8  (0.4) 3.5  (0.4)
17.Secondary Outcome
Title Verbal Learning and Memory: List B
Hide Description 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.
Time Frame Endpoint (12 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat Analysis
Arm/Group Title Placebo Pimozide Active Pimozide
Hide Arm/Group Description:
Half of the subjects were randomized to placebo group.
Half of the subjects are randomized to the active drug.
Overall Number of Participants Analyzed 14 14
Mean (Standard Deviation)
Unit of Measure: words
3.4  (0.6) 3.9  (0.6)
18.Secondary Outcome
Title Trail Making Test: Trail A
Hide Description 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.
Time Frame Baseline
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat Analysis
Arm/Group Title Placebo Pimozide Active Pimozide
Hide Arm/Group Description:
Half of the subjects were randomized to placebo group.
Half of the subjects are randomized to the active drug.
Overall Number of Participants Analyzed 14 14
Mean (Standard Deviation)
Unit of Measure: seconds
3.7  (0.1) 3.8  (0.1)
19.Secondary Outcome
Title Trail Making Test: Trail A
Hide Description

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.)

Time Frame Endpoint (12 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat Analysis
Arm/Group Title Placebo Pimozide Active Pimozide
Hide Arm/Group Description:
Half of the subjects were randomized to placebo group.
Half of the subjects are randomized to the active drug.
Overall Number of Participants Analyzed 14 14
Mean (Standard Deviation)
Unit of Measure: seconds
3.6  (0.1) 3.8  (0.1)
20.Secondary Outcome
Title Trail Making Test: Trail B
Hide Description

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.)

Time Frame Baseline
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat Analysis
Arm/Group Title Placebo Pimozide Active Pimozide
Hide Arm/Group Description:
Half of the subjects were randomized to placebo group.
Half of the subjects are randomized to the active drug.
Overall Number of Participants Analyzed 14 14
Mean (Standard Deviation)
Unit of Measure: seconds
4.6  (0.2) 4.9  (0.2)
21.Secondary Outcome
Title Trail Making Test: Trail B
Hide Description

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.)

Time Frame Endpoint (12 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat Analysis
Arm/Group Title Placebo Pimozide Active Pimozide
Hide Arm/Group Description:
Half of the subjects were randomized to placebo group.
Half of the subjects are randomized to the active drug.
Overall Number of Participants Analyzed 14 14
Mean (Standard Deviation)
Unit of Measure: seconds
4.6  (0.2) 4.9  (0.2)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Pimozide Active Pimozide
Hide Arm/Group Description Half of the subjects were randomized to placebo group. Half of the subjects are randomized to the active drug.
All-Cause Mortality
Placebo Pimozide Active Pimozide
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Pimozide Active Pimozide
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/14 (0.00%)      0/14 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Pimozide Active Pimozide
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/14 (7.14%)      1/14 (7.14%)    
Cardiac disorders     
QTc Prolongation  1/14 (7.14%)  1 1/14 (7.14%)  1
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Handan Gunduz-Bruce MD
Organization: Yale University School of Medicine, Dept of Psychiatry
Phone: (203) 932-5711 ext 4130
Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT00374244     History of Changes
Other Study ID Numbers: 02T-251
First Submitted: September 7, 2006
First Posted: September 11, 2006
Results First Submitted: January 10, 2013
Results First Posted: March 4, 2016
Last Update Posted: March 4, 2016