Addition of Ondansetron to Ongoing Antipsychotic Treatment for Schizophrenia

Study Overview
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Brief Summary
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This study will examine the effects of ondansetron on auditory nerve activity in people with schizophrenia who are being treated with new antipsychotics.

Detailed Description
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Schizophrenia is a devastating brain disorder. Most people with schizophrenia have difficulty filtering out unimportant auditory information. They have an inability to appropriately inhibit, or gate, sensory information that enters the ear. Standard treatments do not address this problem. When the drug ondansetron is taken in addition to typical antipsychotic drugs, P50 auditory gating improves. However, ondansetron has not been used with some of the newer, atypical antipsychotic drugs. This study will evaluate the effect of combining ondansetron with newer, atypical antipsychotic drugs on P50 auditory gating. Participants in this double-blind study will be randomly assigned to receive either ondansetron or placebo for 3 months. Upon completion of the first 3 months, participants will be crossed over to receive the other treatment for an additional 3 months. All participants will also take an atypical antipsychotic drug, including olanzapine, quetiapine, or aripiprazole. Auditory gating will be assessed using computerized cognitive testing and functional magnetic resonance imaging (fMRI) at baseline and Months 3 and 6. Vital signs and evoked potentials will be assessed at Weeks 1, 3, and 6. Clinical symptoms and cognitive abilities will also be evaluated to determine the effectiveness of ondansetron.

Official Title
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Atypical Antipsychotics and P50 Sensory Gating

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Ondansetron followed by placebo
* Drug: Placebo followed by Ondansetron


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meets DSM-IV criteria for schizophrenia Stable, chronic schizophrenia Currently taking atypical medications Use of effective form of contraception throughout study Exclusion Criteria: History of any alcohol or drug abuse within 3 months of study start date Any other major neurological disorders History of or current head trauma Any medical conditions affecting the central nervous system Current epilepsy, asthma, migraine headache, previous myocardial infarction, stroke, diabetes, hypertension, narrow angle glaucoma, or neuromuscular illnesses Pregnant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ondansetron followed by placebo<br>Participants will take ondansetron then placebo plus an atypical antipsychotic drug | Drug: Ondansetron followed by placebo<br>* Participants will take 16mg of ondansetron daily for the first three months followed by 3 months of placebo. An atypical antipsychotic drug (olanzapine,quetiapine, or aripiprazole) will also be taken throughout the 6 months treatment period.<br>* Other names: Zofran, Zuplenz;|
| Experimental: Placebo followed by Ondansetron<br>Participants will take placebo then ondansetron plus an atypical antipsychotic drug | Drug: Placebo followed by Ondansetron<br>* Participants will take placebo daily for the first three months followed by 3 months of 16mg of ondansetron daily. An atypical antipsychotic drug (olanzapine,quetiapine, or aripiprazole) will also be taken throughout the 6 months treatment period.<br>* Other names: Zofran, Zuplenz;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| P50 Sensory Gating | P50 Sensory Gating as measured by evoked potentials (response to stimuli, in this case, clicking sounds).The P50 potential was identified and measured using a computer algorithm. The amplitude of the P50 test wave was divided by the amplitude of the P50 conditioning wave, expressed as a percentage: the P50 ratio. Lower P50 ratios represent better outcomes. | Up to 3 hours | 
| Cognitive Testing |  | Measured at Months 3 and 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Ondansetron, P50 sensory gating, Evoked potentials, 5-HT3 receptors, Atypical antipsychotics