Treating Schizophrenia by Correcting Abnormal Brain Development

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

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00179465

Enrollment

Registered

2005-09-16

Start date

2003-11-30

Completion date

2026-09-30

Last updated

2025-01-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Schizophrenia

Keywords

Treatment, fMRI, Cognition, Brain development

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.

Interventions

DRUGTiagabine

Up to 36 mg daily

DRUGPlacebo

Placebo

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 25 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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)

Countries

United States

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026