Treating Schizophrenia by Correcting Abnormal Brain Development

Phase 3

Active, not recruiting

• Conditions: Schizophrenia
• Interventions: Drug: Placebo; Drug: Tiagabine

• Registration Number: NCT00179465
• Lead Sponsor: Beth Israel Deaconess Medical Center

Brief Summary

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

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.

Study Timeline

• Study Start: 2003-11
• Study First Submitted: 2005-09-12
• Study First Submitted QC: 2005-09-12
• Study First Posted: 2005-09-16
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-23
• Last Update Posted: 2025-01-27
• Primary Completion: 2026-09
• Study Completion: 2026-09

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 36

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Antipsychotics plus placebo	Placebo	Half of the subjects will receive placebo in addition to their antipsychotic regimen.
Antipsychotic plus study drug	Tiagabine	Half of the subjects will receive the study medications in addition to their ongoing antipsychotic regimen.

Primary Outcome Measures

Name	Time	Method
Neurocognitive Functions-Working Memory	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	Working memory will be assessed using the n-back working memory test
Neurocognitive Functions-Executive Function	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	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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States