Remediation of Impaired Self-Regulation in Patients With Mild TBI

Study Overview
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Brief Summary
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The ability to regulate impulses enables us to plan for the future, to maintain focus in the face of distractions (i.e. to encode memories), and to manage emotions. This self regulation can be compromised in individuals who have a history of mild traumatic brain injury and co-occurring disorders. In this study the investigators are using functional MRI scanning to understand how memory and self regulation are expressed in the brains of people with a history of mild traumatic brain injury. The investigators are also testing whether the medication tolcapone may improve memory and self regulation.

Detailed Description
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In this randomized, double-blind, placebo-controlled, crossover cognitive neuroscience study, the investigators are evaluating whether the COMT inhibitor tolcapone impacts memory and self regulation, as measured both behaviorally (via cognitive testing) and neurophysiologically (via functional MRI). A new study arm that does not include use of tolcapone, nominally equivalent to the placebo arm only, is now also included to address performance on cognitive testing alone.

Official Title
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Remediation of Impaired Self-Regulation in Patients With Mild TBI

Conditions
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Mild Traumatic Brain Injury

Intervention / Treatment
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* Drug: Tolcapone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Veteran ages 18-50 and in general good health; Able to read English at a 6th grade level; Able to provide written informed consent; Normal or corrected to normal visual acuity; Stable doses of all medications (2 weeks or greater); History of mild traumatic brain injury greater than 6 months prior to participation Exclusion Criteria: Contraindications to MRI scanning; Inability to complete basic fMRI requirements; History of brain surgery or penetrating brain injury; Uncontrolled blood pressure (low or high); Contraindications to tolcapone use (not required for subjects who participate only in the study arm that does not include study medication); Use of medications or drugs with dopamine-related actions within 30 days; Active substance abuse or dependence; Clinically severe medical illness requiring treatment; History of psychiatric hospitalization (past 1 year) or suicide attempt (past 5 years); Seizures greater than 4 weeks after TBI event or seizures requiring active treatment; History of brain tumor, stroke, Alzheimer's disease, aneurysm rupture, or multiple sclerosis; History of schizophrenia, ADHD or psychiatric diagnosis EXCEPT depression or PTSD

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Functional MRI Arm<br>This cognitive science study consists of a single arm in which all subjects receive both tolcapone and placebo in randomized, double-blind, counterbalanced, crossover fashion | Drug: Tolcapone<br>* COMT Inhibitor<br>* Other names: Tasmar;Drug: Placebo<br>* A pill that contains no active ingredient<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood Oxygen Level Dependent (BOLD) brain signal measured using functional MRI | BOLD signal provides an indirect measure of brain activity during cognitive testing | Approximately 60-240 minutes following tolcapone/placebo administration | 
| Performance on Cognitive Testing | Tasks to assess cognition will be performed while subjects are in the MRI scanner | Approximately 60-240 minutes following tolcapone/placebo administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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concussion, traumatic brain injury, MRI, memory, tolcapone