Efficacy of Pimozide Augmentation for Clozapine Partial Response

NCT00374244 | Completed Phase 2 Results

• 1 other identifier: 02T-251
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 2

Brief Summary

This is a 12 week outpatient study for patients with schizophrenia who are on Clozapine, but continue to experience symptoms. The purpose of this project is to find out if small doses of pimozide (an antipsychotic medication, taken by mouth) will be helpful in reducing symptoms (such as hearing voices, having trouble in organizing your thoughts, lack of interest in life events and social activities), compared to placebo (an inactive substance, "sugar pill"), when added to clozapine in patients with schizophrenia. The participant will be asked to come in once a week to meet with the research staff and study doctor. The participant will continue to see your regular clinician during this study for all normal appointments. The participant will remain on your current medications throughout the study. During the study you will be randomly selected to be put on a small dose of Pimozide or placebo.

Conditions

Schizophrenia

Keywords

schizophrenia; pimozide; clozapine

Outcome Measures

Primary Outcomes (4)

• Brief Psychiatric Rating Scale (BPRS) Total Score

  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.

  Baseline

• Brief Psychiatric Rating Scale (BPRS) Total Score

  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.

  Endpoint (12 weeks)

• Scale for the Assessment of Negative Symptoms (SANS)

  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.

  baseline

• Scale for the Assessment of Negative Symptoms (SANS)

  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.

  Endpoint (12 weeks)

Secondary Outcomes (17)

• CGI Severity of Illness Scale (CGI-S)

  baseline

• CGI Severity of Illness Scale (CGI-S)

  Endpoint (12 weeks)

• CGI Improvement Scale (CGI-I)

  Endpoint (12 weeks)

• Verbal Fluency

  Baseline

• Verbal Fluency

  Endpoint (12 weeks)

Study Arms (2)

1

PLACEBO COMPARATOR

placebo pimozide

Drug: placebo

2

ACTIVE COMPARATOR

active pimozide

Drug: Pimozide

Interventions

Pimozide DRUG

half of the subjects are randomized to the active drug group

2

placebo DRUG

half of the subjects are randomized to placebo group

1

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosis of schizophrenia or schizoaffective disorder.
• A minimum Brief Psychiatric Rating Scale (BPRS) score of 35 and a BPRS psychotic symptom cluster score of at least 8.
• Currently taking clozapine with a blood level between 350-1000 ng/ml and on a stable dose of clozapine for the past 2 weeks.
• Able to give informed consent.

You may not qualify if:

• A history of significant medical/neurological disease such as thyroid, renal, hepatic abnormality, seizure disorder.
• History of Neuroleptic Malignant Syndrome.
• Current substance abuse determined by urine toxicology.
• Cardiac arrhythmia, sinus bradycardia (heart rate less than 60/min), sinus tachycardia (heart rate greater than 110/min), supraventricular tachycardia, ventricular tachycardia, Wolff-Parkinson-White Syndrome, first, second, third degree atrioventricular (AV) block, atrial fibrillation, atrial flutter and junctional complexes. in baseline electrocardiogram (EKG). Study doctors will examine the EKGs and consult with an internist/cardiologist as needed.
• on EKG: QTc \> 450 ms.
• Current use of macrolide antibiotics (e.g., erythromycin, clarithromycin), azole antifungal agents (e.g., ketoconazole, itraconazole), protease inhibitors (e.g., ritonavir, indinavir), nefazodone, and other medications that are associated with prolonged QTc.
• Current use of antipsychotics other than clozapine.
• Current use of sertraline.
• IQ level below 70.
• At high risk for suicidal/homicidal behavior.
• Pregnancy, lack of birth control for females of childbearing age (female patients must report use of effective method for birth control such as birth control pills, condoms, barrier methods, abstinence or have written statement from their doctors that they are medically sterile).
• Non-English speaking.

Sponsors & Collaborators

• Yale University: lead
• Stanley Medical Research Institute: collaborator

Study Sites (2)

Connecticut Mental Health Center

New Haven, Connecticut, 06508, United States

Location

VA Connecticut Healthcare System

West Haven, Connecticut, 06516, United States

Location

MeSH Terms

Conditions

Schizophrenia

Interventions

Pimozide

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Handan Gunduz-Bruce MD
• Organization: Yale University School of Medicine, Dept of Psychiatry

handan.gunduz-bruce@yale.edu

(203) 932-5711

Study Officials

• Handan Gunduz-Bruce, MD

  Yale University School of Medicine, Dept of Psychiatry

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2006
• First Posted: September 11, 2006
• Study Start: January 1, 2004
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: March 4, 2016
• Results First Posted: March 4, 2016

Record last verified: 2016-02

Locations

US (2)