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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Joseph Friedman, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:
NCT00158223
First received: September 7, 2005
Last updated: April 7, 2015
Last verified: April 2015
  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 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pimozide Augmentation of Clozapine in Schizophrenia

Resource links provided by NLM:


Further study details as provided by Icahn School of Medicine at Mount Sinai:

Primary Outcome Measures:
  • Positive Syndrome Scale (PANSS) Total Score [ Time Frame: Variable change from baseline to week 12 ] [ Designated as safety issue: Yes ]
    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.

  • Negative Syndrome Scale (PANSS) Total Score [ Time Frame: Variable change from baseline to week 12 ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Clinical Global Impression of Change (CGIC) [ Time Frame: variable change from baseline to week 12 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 76
Study Start Date: October 2004
Study Completion Date: February 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Orap

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00158223

Locations
United States, New York
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
Manhattan Psychiatric Center
New York, New York, United States, 10035
Pilgrim Psychiatric Center
W. Brentwood, New York, United States, 11717
Sponsors and Collaborators
Icahn School of Medicine at Mount Sinai
Investigators
Principal Investigator: Joseph I. Friedman, MD Icahn School of Medicine at Mount Sinai
  More Information

Publications:
Responsible Party: Joseph Friedman, Associate Professor, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier: NCT00158223     History of Changes
Other Study ID Numbers: GCO 02-0517, R01MH067806
Study First Received: September 7, 2005
Results First Received: September 3, 2013
Last Updated: April 7, 2015
Health Authority: United States: Federal Government

Keywords provided by Icahn School of Medicine at Mount Sinai:
Schizophrenia
Clozapine
Treatment
Combination
Unresponsive
Schizoaffective Disorders

Additional relevant MeSH terms:
Mental Disorders
Psychotic Disorders
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Clozapine
Pimozide
Anti-Dyskinesia Agents
Antipsychotic Agents
Central Nervous System Agents
Central Nervous System Depressants
Dopamine Agents
Dopamine Antagonists
GABA Agents
GABA Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Antagonists
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on July 27, 2015