Treating Schizophrenia by Correcting Abnormal Brain Development

• Sponsor: Beth Israel Deaconess Medical Center (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT00179465
• Collaborator: Dartmouth-Hitchcock Medical Center (Other)
• Enrollment: 36
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 226
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: Tiagabine; Drug: Placebo	Phase 3

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Nov 1, 2003
• Anticipated Primary Completion Date: Sep 1, 2022
• Anticipated Study Completion Date: Sep 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Antipsychotic plus study drug Half of the subjects will receive the study medications in addition to their ongoing antipsychotic regimen.	Drug: Tiagabine; Up to 36 mg daily; Other Names: Antipsychotic
Placebo Comparator: Antipsychotics plus placebo Half of the subjects will receive placebo in addition to their antipsychotic regimen.	Drug: Placebo; Placebo; Other Names: Antipsychotic

Outcome Measures

Primary Outcome Measures

1. 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

2. 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

1. 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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 25 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Beth Israel Deaconess Medical Center
• Dartmouth-Hitchcock Medical Center

Investigators

• Principal Investigator: T.-U. Wilson Woo, M.D., Ph.D., Beth Israel Deaconess Medical Center, Harvard Medical School

Study Documents (Full-Text)

None provided.

More Information

Publications

• Woo TU, Crowell AL. Targeting synapses and myelin in the prevention of schizophrenia. Schizophr Res. 2005 Mar 1;73(2-3):193-207. Review.
• 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.
• 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.

• Responsible Party: Tsung-Ung Wilson Woo, Assistant Professor of Psychiatry, Beth Israel Deaconess Medical Center
• ClinicalTrials.gov Identifier: NCT00179465
• Other Study ID Numbers: 2004P000078
• First Posted: Sep 16, 2005
• Last Update Posted: May 11, 2021
• Last Verified: May 1, 2021

• Keywords provided by Tsung-Ung Wilson Woo, Assistant Professor of Psychiatry, Beth Israel Deaconess Medical Center: Treatment; fMRI; Cognition; Brain development
• Additional relevant MeSH terms: Schizophrenia; Tiagabine; Antipsychotic Agents

Study Results

No Results Posted as of May 11, 2021