Treating Schizophrenia by Correcting Abnormal Brain Development

Study Overview
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Brief Summary
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The purpose of this study is to determine whether treatment with tiagabine (Gabitril) during the early course of schizophrenia can fundamentally correct the brain deficits associated with the disease. This study is funded by the National Institutes of Health.

Detailed Description
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It is hypothesized that enhancement of GABA neurotransmission during the early course of the illness by tiagabine (Gabitril), a GABA transporter GAT-1-specific inhibitor and a FDA-approved anticonvulsant, will improve both clinical symptoms and working memory in schizophrenia. This improvement is postulated to be the result of tiagabine-mediated modification of the developmental synaptic pruning of prefrontal cortical circuitry. The occurrence of circuitry modification after tiagabine treatment will be assessed by the following independent methodologic approaches: MRI morphometric analysis of prefrontal gray matter volume and fMRI measurements of brain activity patterns during performance of tasks that probe working memory.

Official Title
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Addition of Tiagabine to Second-Generation Antipsychotics in the Treatment of Recent-Onset Schizophrenia by Modification of Developmental Reorganization of the Prefrontal Cortex

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Tiagabine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meets criteria for the diagnosis of schizophrenia, with onset of psychotic symptoms within the past 3 years. Currently on second-generation antipsychotics for at least 3 months. Age 18-25, otherwise healthy. Exclusion Criteria: Diagnosis of schizoaffective disorder. Has failed two or more clinically adequate antipsychotic trials. History of seizures or any neurologic disorders. Pregnant or nursing women. Known HIV infection. Actively suicidal. History of any substance dependence. Currently meets criteria for substance abuse/dependence. Other MRI exclusion criteria per Radiology Department protocols.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 25 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: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Antipsychotic plus study drug<br>Half of the subjects will receive the study medications in addition to their ongoing antipsychotic regimen. | Drug: Tiagabine<br>* Up to 36 mg daily<br>* Other names: Antipsychotic;|
| Placebo Comparator: Antipsychotics plus placebo<br>Half of the subjects will receive placebo in addition to their antipsychotic regimen. | Drug: Placebo<br>* Placebo<br>* Other names: Antipsychotic;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurocognitive Functions-Working Memory | Working memory will be assessed using the n-back working memory test | Working memory will be assessed at baseline and at 6-month time point to see if working memory changes after 6 months compared to baseline measurement | 
| Neurocognitive Functions-Executive Function | Executive function, which is a complex form of working memory, will be assessed using the MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) battery | Executive function will be assessed at baseline and at 6-month time point to see if executive function changes after 6 months compared to baseline measure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical symptoms | Positive and negative symptoms will be quantified using PANSS (positive and negative symptom scale) | Symptoms will be assessed at baseline and at 6-month time point to see if symptoms change after 6 months compared to baseline measures | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment, fMRI, Cognition, Brain development