Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia

April 7, 2015 updated by: Joseph Friedman, Icahn School of Medicine at Mount Sinai

Pimozide Augmentation of Clozapine in Schizophrenia

This study will assess the effectiveness of pimozide in enhancing the effects of clozapine in the treatment of schizophrenia.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

A significant number of schizophrenics exhibit partial or no response to typical antipsychotic medications. Clozapine has been shown to be more effective in treating schizophrenia than typical antipsychotic drugs. However, only an estimated 30% to 60% of people who are unresponsive to treatment with typical antipsychotics will respond to treatment with clozapine. Taking clozapine with pimozide, an antipsychotic drug, can increase clozapine's effects. However, sufficient research on this approach has not yet been performed. This study will assess the effectiveness of pimozide in enhancing the effects of clozapine in the treatment of schizophrenia.

Participants in this double-blind study will receive a stable dose of clozapine for eight weeks prior to enrollment. For the first 4 weeks following enrollment, baseline measurements will be taken. Once a week, participants will report to the study site, where symptom severity, cognitive ability, and functional status, including reading level, will be assessed. In addition, participants will receive a standard medical examination, which will include blood tests and an EKG. Upon completion of this initial phase, participants will be randomly assigned to one of two treatment groups: clozapine combined with pimozide; or clozapine combined with placebo. This phase will last for 12 weeks. Study visits will continue to occur weekly, and will be used to re-assess the measurements obtained during baseline. In addition, participants will have an EKG at each study visit for the first 4 weeks of treatment. All baseline measurements will be repeated in Week 12.

Study Type

Interventional

Enrollment (Actual)

76

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10029
        • Icahn School of Medicine at Mount Sinai
      • New York, New York, United States, 10035
        • Manhattan Psychiatric Center
      • W. Brentwood, New York, United States, 11717
        • Pilgrim Psychiatric Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosis of schizophrenia according to DSM-IV criteria
  • Any schizoaffective disorder or subtype
  • Score greater than 60 on the Positive and Negative Syndrome Scale (PANSS)
  • Currently taking clozapine
  • Score of four or higher on two or more items from the positive symptom subscale of the PANSS
  • Score of 4 or greater on the Clinical Global Impression (CGI) scale
  • Clozapine plasma level greater than 378 µg/ml
  • Stable dose of clozapine demonstrated to have been associated with a clozapine plasma level greater than 378 µg/ml for at least eight weeks
  • Able to read at an 8th grade level or above

Exclusion Criteria:

  • History of unstable coronary artery disease
  • Congestive heart failure
  • History of long Q-T syndrome
  • History of cardiac arrhythmia
  • History of cardiac conduction delay
  • Baseline QT correction score greater than 0.425 seconds
  • Liver disease
  • History of stroke
  • History of Neuroleptic Malignant Syndrome
  • Hypokalemia
  • Hypocalcemia
  • Current blindness, deafness, language difficulties, or any other disability which may prevent participation or cooperation in the study
  • Current suicidal or homicidal thoughts
  • Currently abusing psychoactive substances
  • Currently receiving antidepressants, thymoleptics, L-DOPA, buspirone, or antipsychotics other than clozapine (Valproic acid and Divalproex sodium are not criteria for exclusion)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: placebo
Participants will receive encapsulated placebo made to match active drug
Drug: Placebo
Active drug and placebo will be encapsulated in an identical fashion. The placebo capsule will be made to match in appearance and weight. There will be flexible dosing, allowing a minimum of 1 capsule per day to 4 capsules per day, in order to match the dosing range of the active treatment.
Other Names:
  • Sugar Pill
Experimental: pimozide
Participants will receive pimozide flexible dosing
Drug: Pimozide
Each capsule of active treatment will contain 2 mg of pimozide. Dosing will be flexible and will range from a minimum of 2 mg per day to 8 mg per day. Dosing will begin at Week 1 with 1 capsule per day. This will be slowly titrated at a rate of 1 capsule per week to a maximum of 4 capsules depending upon clinical response and side effects.
Other Names:
  • Orap

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Positive Syndrome Scale (PANSS) Total Score
Time Frame: Variable change from baseline to week 12
Severity of positive schizophrenic symptoms The Positive Syndrome Scale of the PANSS is comprised of seven items measuring positive such symptoms such as hallucinations, delusions, grandiosity, etc. Each item is scored on a 7 point scale of that particular symptom's severity, ranging from 1 = absent, 2 = minimal, 3 = mild, 4 = moderate, 5 = moderate severe, 6 = severe, and 7 = extreme. The PANSS Positive Subscale seven items has a range of a summed score from 7 (absent) to 49 (extreme psychopathology). Therefore, the higher the score, the more severe the symtpoms.
Variable change from baseline to week 12
Negative Syndrome Scale (PANSS) Total Score
Time Frame: Variable change from baseline to week 12
Severity of negative schizophrenic symptoms, The Negative Syndrome scale is compromised of seven items, each scored on severity with numeric assignments ranging from 1 = absent, 2 = minimal, 3 = mild, 4 = moderate, 5 = moderate severe, 6 = severe, and 7 = extreme. The items which comprise the Negative Syndrome Scale of the PANSS measure things such as emotional withdrawal, apathy, difficulty in abstract thinking, etc. The seven items which comprise the PANSS Negative Subscale has an aggregate range of 7 (absent) to 49 (extreme psychopathology), a higher score indicating more severe symptoms.
Variable change from baseline to week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Global Impression of Change (CGIC)
Time Frame: variable change from baseline to week 12
The Clinical Global Impression-improvement (CGI-improvement) scale is a research rating tool, developed for use in NIMH-sponsored clinical trials provides a brief assessment of the clinician's view of the patient's overall clinical improvement prior to and after initiating a study medication. The CGI-change is rated on a seven point scale ranging from 1= very much improved since the initiation of treatment to 7=very much worse since the initiation of treatment. Therefore, a lower score indicates more improvement in symptoms over time.
variable change from baseline to week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Icahn School of Medicine at Mount Sinai

Collaborators

National Institute of Mental Health (NIMH)

Investigators

  • Principal Investigator: Joseph I. Friedman, MD, Icahn School of Medicine at Mount Sinai

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2004

Primary Completion (Actual)

February 1, 2009

Study Completion (Actual)

February 1, 2009

Study Registration Dates

First Submitted

September 7, 2005

First Submitted That Met QC Criteria

September 7, 2005

First Posted (Estimate)

September 12, 2005

Study Record Updates

Last Update Posted (Estimate)

April 9, 2015

Last Update Submitted That Met QC Criteria

April 7, 2015

Last Verified

April 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GCO 02-0517
  • R01MH067806 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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