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

September 7, 2005
April 7, 2015
October 2004
February 2009   (final data collection date for primary outcome measure)
  • 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.
Positive and Negative Syndrome Scale (PANSS) total score; measured weekly
Complete list of historical versions of study NCT00158223 on ClinicalTrials.gov Archive Site
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.
Clinical Global Impression of Change (CGIC); measured weekly
Not Provided
Not Provided
 
Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Schizophrenia
  • Psychotic Disorders
  • 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
  • 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
  • Placebo Comparator: placebo
    Participants will receive encapsulated placebo made to match active drug
    Intervention: Drug: Placebo
  • Experimental: pimozide
    Participants will receive pimozide flexible dosing
    Intervention: Drug: Pimozide

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
76
February 2009
February 2009   (final data collection date for primary outcome measure)

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)
Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00158223
GCO 02-0517, R01MH067806
Yes
Joseph Friedman, Mount Sinai School of Medicine
Mount Sinai School of Medicine
National Institute of Mental Health (NIMH)
Principal Investigator: Joseph I. Friedman, MD Mount Sinai School of Medicine
Mount Sinai School of Medicine
April 2015

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