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Completed

NCT Number: NCT02260570

Remediation of Impaired Self-Regulation in Patients With Mild TBI

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.

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Key information

Conditions

Mild Traumatic Brain Injury Brain Concussion Brain Diseases Brain Injuries Brain Injuries, Traumatic Central Nervous System Diseases Craniocerebral Trauma Head Injuries, Closed Mental Disorders Nervous System Diseases Stress Disorders, Post-Traumatic Stress Disorders, Traumatic Trauma and Stressor Related Disorders Trauma, Nervous System Wounds and Injuries Wounds, Nonpenetrating

Age range

18 year–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Early Phase 1

Primary location

VA Northern California Health Care System, Mather, CA

Sacramento, California, 95655, United States

About this study

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).

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Tolcapone

Drug

COMT Inhibitor

Other names: Tasmar

Placebo

Drug

A pill that contains no active ingredient

Primary outcomes

  1. Blood Oxygen Level Dependent (BOLD) Brain Signal Measured Using Functional MRI.

    Time frame: Approximately 60-240 minutes following tolcapone/placebo administration

    Functional MRI measures blood flow changes. Blood Oxygen Level Dependent (BOLD) signals provide an indirect unitless measure of brain activity typically described as a percentage. However, because fMRI data sets are large (> 10,000 comparisons), analysis packages present results as F statistics or similar measures for individual voxels across the brain. Thus, no single mean or median value describes the 3-way interaction between drug (tolcapone minus placebo), stimulus emotion (neutral versus anxious), and CAPS-score with degrees of freedom = [1,1,60]. Because each subject serves as his/her own control, drug results are also intrinsically paired -- i.e. data are presented for participants as tolcapone minus placebo results within subject. The data values below represent the number of above-threshold, neighboring voxels in the largest clusters of voxels in the brain for the patient group as a whole, not separately for each participant.

  2. Performance on Cognitive Testing

    Time frame: Approximately 60-240 minutes following tolcapone/placebo administration

    Tasks to assess cognition were performed while subjects are scanned. Signal detection theory (SDT) assesses the ability of subjects to accurately recall working memory memoranda. In SDT, the sensitivity index d' results from subtracting the normalized false alarm rate from the normalized hit rate; thus, higher values of d' indicate better working memory performance.

    Here we evaluate the interaction with respect to d' between drug condition (tolcapone minus placebo) and Post-Traumatic Stress Disorder severity as measured by the total score on the *Clinician Administered PTSD Scale*, or CAPS. Total CAPS scores range from 0 to 80, with higher scores indicating greater PTSD severity. Because each subject serves as his/her own control, drug results for behavior are intrinsically paired -- i.e. data are presented for participants as tolcapone minus placebo results, as prespecified in the statistical analysis plan.

Sponsors and collaborators

Lead sponsor

VA Office of Research and Development

Fed

Collaborators

  • University of California, Berkeley
  • University of California, San Francisco

Registry information

Important dates

Study start
2015
Primary completion
2021
Study completion
2021
First posted
Oct 9, 2014
Registry last updated
Sep 22, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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