Remediation of Impaired Self-Regulation in Patients With Mild TBI

VA Office of Research and Development

Status and phase: Completed; Early Phase 1

Conditions: Mild Traumatic Brain Injury

Treatments: Drug: Placebo; Drug: Tolcapone

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT02260570

1I01RX000825-01 (U.S. NIH Grant/Contract)

D0825-I

Details and patient eligibility

About

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.

Full description

In this randomized, double-blind, placebo-controlled, crossover cognitive neuroscience study, the investigators are evaluating whether the catechol-O-methyltransferase (COMT) inhibitor tolcapone impacts memory and self regulation, as measured both behaviorally (via cognitive testing) and neurophysiologically (via functional MRI).

Enrollment: 55 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

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 magnetic resonance imaging (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;
• 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 traumatic brain injury (TBI) event or seizures requiring active treatment;
• History of brain tumor, stroke, Alzheimer's disease, aneurysm rupture, or multiple sclerosis;
• History of schizophrenia, attention deficit hyperactivity disorder (ADHD) or psychiatric diagnosis EXCEPT depression or post-traumatic stress disorder (PTSD)

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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55 participants in 2 patient groups

Functional MRI Arm 1: Tolcapone first, then placebo

Experimental group

Description:

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. Subjects have been divided into two arms based on the order in which they received the drug intervention. Because baseline dopamine levels can vary substantially between individuals, this grouping by sequence rather than by drug condition retains the within-subject information necessary for subsequent analyses.

Treatment:

Drug: Tolcapone

Drug: Placebo

Functional MRI Arm 2: Placebo first, then tolcapone

Experimental group

Description:

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. Subjects have been divided into two arms based on the order in which they received the drug intervention. Because baseline dopamine levels can vary substantially between individuals, this grouping by sequence rather than by drug condition retains the within-subject information necessary for subsequent analyses.

Treatment:

Drug: Tolcapone

Drug: Placebo