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Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
This study is currently recruiting participants.
Verified by National Institute of Mental Health (NIMH), October 2008
Sponsored by: National Institute of Mental Health (NIMH)
Information provided by: National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier: NCT00158223
  Purpose

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


Condition Intervention Phase
Schizophrenia
Psychotic Disorders
Drug: Pimozide
Drug: Placebo
Phase IV

MedlinePlus related topics: Psychotic Disorders Schizophrenia
Drug Information available for: Clozapine Pimozide
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title: Pimozide Augmentation of Clozapine in Schizophrenia

Further study details as provided by National Institute of Mental Health (NIMH):

Primary Outcome Measures:
  • Positive and Negative Syndrome Scale (PANSS) total score [ Time Frame: Measured weekly for 12 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Clinical Global Impression of Change (CGIC) [ Time Frame: Measured weekly for 12 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 64
Study Start Date: October 2004
Estimated Study Completion Date: February 2009
Estimated Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
2: Placebo Comparator
Participants will receive encapsulted 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 eill be felixble 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.
1: Experimental
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00158223

Contacts
Contact: Joseph I. Friedman, MD 631-761-3607

Locations
United States, New York
The Mount Sinai Hospital Recruiting
New York, New York, United States, 10029
Contact: Mariangela Cavagna     212-659-9223     mariangela.cavagna@mssm.edu    
Principal Investigator: Joseph I. Friedman, MD            
Pilgrim Psychiatric Center Recruiting
W. Brentwood, New York, United States, 11717
Contact: Michelle Bergman     631-761-2717     PGMDMIL@omh.state.ny.us    
Principal Investigator: Joseph I. Friedman, MD            
Manhattan Psychiatric Center Recruiting
New York, New York, United States, 10035
Contact: Frances Alcantara     646-672-6173     Marcffa@omh.state.ny.us    
Principal Investigator: Jean-Pierre I. Lindenmayer, MD            
Sponsors and Collaborators
Investigators
Principal Investigator: Joseph I. Friedman, MD Mount Sinai School of Medicine
  More Information

Publications:
Responsible Party: Mount Sinai School of Medicine ( Joseph I. Friedman )
Study ID Numbers: R01 MH67806, DSIR 83-ATAP
Study First Received: September 7, 2005
Last Updated: October 23, 2008
ClinicalTrials.gov Identifier: NCT00158223  
Health Authority: United States: Federal Government

Keywords provided by National Institute of Mental Health (NIMH):
Schizophrenia
Clozapine
Treatment
Combination
Unresponsive
Schizoaffective Disorders

Study placed in the following topic categories:
Schizophrenia
Dopamine
Mental Disorders
Clozapine
Psychotic Disorders
Pimozide
Serotonin
Schizophrenia and Disorders with Psychotic Features

Additional relevant MeSH terms:
Neurotransmitter Agents
Tranquilizing Agents
Molecular Mechanisms of Pharmacological Action
Anti-Dyskinesia Agents
Physiological Effects of Drugs
Psychotropic Drugs
Central Nervous System Depressants
Dopamine Antagonists
Antipsychotic Agents
Pharmacologic Actions
GABA Antagonists
Serotonin Antagonists
Serotonin Agents
Therapeutic Uses
GABA Agents
Dopamine Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 30, 2009