Remediation of Impaired Self-Regulation in Patients With Mild TBI

Sponsor

VA Office of Research and Development (U.S. Fed)

Overall Status

Completed

CT.gov ID

NCT02260570

Collaborator

University of California, Berkeley (Other), University of California, San Francisco (Other)

Enrollment

Location

Arm

Actual Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Mild Traumatic Brain Injury	Drug: Tolcapone Drug: Placebo	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

55 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Basic Science

Official Title:

Remediation of Impaired Self-Regulation in Patients With Mild TBI

Actual Study Start Date :

Aug 1, 2015

Actual Primary Completion Date :

Jun 30, 2021

Actual Study Completion Date :

Jun 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Functional MRI Arm 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 COMT Inhibitor Other Names: Tasmar Drug: Placebo A pill that contains no active ingredient

Arm

Intervention/Treatment

Experimental: Functional MRI Arm

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

COMT Inhibitor

Other Names:

Tasmar

Drug: Placebo

A pill that contains no active ingredient

Outcome Measures

Primary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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