Clinical trial NCT00179465: Treating Schizophrenia by Correcting Abnormal Brain Development
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Schizophrenia
Keywords: Treatment
fMRI
Cognition
Brain development
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
Collaborators: name: Dartmouth-Hitchcock Medical Center
First posted: 2005-09-16
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 25
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Neurocognitive Functions-Working Memory
timeFrame: 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
measure: Neurocognitive Functions-Executive Function
timeFrame: 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 outcomes:
measure: Clinical symptoms
timeFrame: Symptoms will be assessed at baseline and at 6-month time point to see if symptoms change after 6 months compared to baseline measures
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School
name: T.-U. Wilson Woo, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
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.