Efficacy of Pimozide Augmentation for Clozapine Partial Response

This study has been completed.
Sponsor:
Collaborator:
Stanley Medical Research Institute
Information provided by (Responsible Party):
Handan Gunduz-Bruce, Yale University
ClinicalTrials.gov Identifier:
NCT00374244
First received: September 7, 2006
Last updated: April 26, 2012
Last verified: January 2012
  Purpose

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.


Condition Intervention Phase
Schizophrenia
Drug: Pimozide
Drug: placebo
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Brief Psychiatric Rating Scale (BPRS) [ Time Frame: baseline and monthly ] [ Designated as safety issue: No ]
  • Scale for the Assessment of Negative Symptoms (SANS) [ Time Frame: baseline and monthly ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Clinical Global Impression (CGI) [ Time Frame: Baseline and monthly ] [ Designated as safety issue: No ]
  • Brief neurocognitive battery [ Time Frame: Baseline and monthly ] [ Designated as safety issue: No ]
  • QTC changes [ Time Frame: Baseline and weekly ] [ Designated as safety issue: Yes ]

Enrollment: 29
Study Start Date: January 2004
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 1
placebo pimozide
Drug: placebo
half of the subjects are randomized to placebo
Active Comparator: 2
active pimozide
Drug: Pimozide
half of the subjects are randomized to the active drug

Detailed Description:

If you choose to participate, you will first have screening tests to find out if you are eligible. The study physician will do a number of tests including a physical examination, a routine medical history, lab tests for blood and urine, and EKG (to monitor your heart) and interviews about your physical and mental health.

At each visit you will complete an EKG (to monitor your heart), vital signs, and discuss how you are feeling with the research staff and doctor. Once a month, we will also conduct a slightly longer interview with you about your symptoms and draw one tube of blood to check your Clozapine level. At the beginning and end of the study, you will do some pencil and paper games called "Neurocognitive tests".

If you are interested in participating in this study, we will go over it in greater detail with you, including the possible benefits and risks associated with participating. We will make sure you understand the study before you begin. This study is completely voluntary, which means that you can choose to stop participating in the study at any time.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00374244

Locations
United States, Connecticut
Connecticut Mental Health Center
New Haven, Connecticut, United States, 06508
VA Connecticut Healthcare System
West Haven, Connecticut, United States, 06516
Sponsors and Collaborators
Yale University
Stanley Medical Research Institute
Investigators
Principal Investigator: Handan Gunduz-Bruce, MD Yale University School of Medicine, Dept of Psychiatry
  More Information

No publications provided

Responsible Party: Handan Gunduz-Bruce, Assistant Clinical Professor, Yale University
ClinicalTrials.gov Identifier: NCT00374244     History of Changes
Other Study ID Numbers: 02T-251
Study First Received: September 7, 2006
Last Updated: April 26, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Yale University:
schizophrenia
pimozide
clozapine

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

ClinicalTrials.gov processed this record on April 20, 2014