Reducing Hippocampal Hyperactivity and Improving Cognition in Schizophrenia

Study Overview
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Brief Summary
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This study plans to learn more about the effects of levetiracetam (LEV) on brain activity and cognition in schizophrenia and schizoaffective disorder. Levetiracetam is an anti-seizure drug, also called an anticonvulsant.

Detailed Description
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Cognitive symptoms are not currently well-managed in Veterans with schizophrenia, leading to substantially diminished quality of life. Improved treatment strategies clearly are needed. Recent studies suggest taht an overactive hippocampus is associated with cognitive deficits in the illness. Based on findings that the anti-epileptic drug levetiracetam (LEV) reduces hippocampal activity and improves cognition in other clinical populations while being safe and well-tolerated, this study will examine the effects of the drug on hippocampal activity and cognition in Veterans with schizophrenia. In this crossover design, participants will take LEV for 4 weeks and placebo pills for 4 weeks, but will not know the order in which they are taking them.

Official Title
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Reducing Hippocampal Hyperactivity and Improving Cognition in Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Levetiracetam
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of schizophrenia or schizoaffective disorder Good general health Normal vital signs (blood pressure, pulse, respiration) Exclusion Criteria: Substance abuse Significant neurological disorders Significant head trauma/injury Pregnancy MRI-specific exclusion criteria, e.g.,: claustrophobia weight>400 lbs metal in the body

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Levetiracetam, Then Placebo<br>4 weeks of levetiracetam administration (125 mg pill, bid), followed by a 4-week washout, then 4 weeks of placebo pill administration (bid). | Drug: Levetiracetam<br>* Anticonvulsant drug<br>* Other names: Keppra;Drug: Placebo<br>* Placebo<br>|
| Experimental: Placebo, Then Levetiracetam<br>4 weeks of placebo administration (bid), followed by a 4-week washout, then 4 weeks of levetiracetam administration (125 mg pill, bid). | Drug: Levetiracetam<br>* Anticonvulsant drug<br>* Other names: Keppra;Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurocognitive function | Cognitive function as measured by the Repeatable Battery for the Assessment of Neurological Status (RBANS) | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resting-state neuronal response | Neuronal response (measured via functional magnetic resonance imaging, fMRI) in the hippocampus during rest. | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia