Treating Schizophrenia by Correcting Abnormal Brain Development

Schizophrenia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00179465
• Other study ID #: 2004P000078
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 2003
• Est. completion date: September 2024

Study information

• Verified date: June 2023
• Source: Beth Israel Deaconess Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 36
• Est. completion date: September 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 25 Years

Eligibility

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.

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• Tiagabine
Up to 36 mg daily
• Placebo
Placebo

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Beth Israel Deaconess Medical Center	Dartmouth-Hitchcock Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (3)

Woo TU, Crowell AL. Targeting synapses and myelin in the prevention of schizophrenia. Schizophr Res. 2005 Mar 1;73(2-3):193-207. doi: 10.1016/j.schres.2004.07.022. — View Citation

Woo TU, Spencer K, McCarley RW. Gamma oscillation deficits and the onset and early progression of schizophrenia. Harv Rev Psychiatry. 2010 May-Jun;18(3):173-89. doi: 10.3109/10673221003747609. — View Citation

Woo TU, Whitehead RE, Melchitzky DS, Lewis DA. A subclass of prefrontal gamma-aminobutyric acid axon terminals are selectively altered in schizophrenia. Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5341-6. doi: 10.1073/pnas.95.9.5341. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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