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Remediation of Impaired Self-Regulation in Patients With Mild TBI

Primary Purpose

Mild Traumatic Brain Injury

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Tolcapone
Placebo
Sponsored by
VA Office of Research and Development
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Mild Traumatic Brain Injury focused on measuring concussion, traumatic brain injury, MRI, memory, tolcapone

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts 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 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

Sites / Locations

  • VA Northern California Health Care System, Mather, CA

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Functional MRI Arm

Arm 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

Outcomes

Primary Outcome Measures

Blood Oxygen Level Dependent (BOLD) brain signal measured using functional MRI
BOLD signal provides an indirect measure of brain activity during cognitive testing
Performance on Cognitive Testing
Tasks to assess cognition will be performed while subjects are in the MRI scanner

Secondary Outcome Measures

Full Information

First Posted
October 6, 2014
Last Updated
February 23, 2022
Sponsor
VA Office of Research and Development
Collaborators
University of California, Berkeley, University of California, San Francisco
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1. Study Identification

Unique Protocol Identification Number
NCT02260570
Brief Title
Remediation of Impaired Self-Regulation in Patients With Mild TBI
Official Title
Remediation of Impaired Self-Regulation in Patients With Mild TBI
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
August 1, 2015 (Actual)
Primary Completion Date
June 30, 2021 (Actual)
Study Completion Date
June 30, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
VA Office of Research and Development
Collaborators
University of California, Berkeley, University of California, San Francisco

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mild Traumatic Brain Injury
Keywords
concussion, traumatic brain injury, MRI, memory, tolcapone

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
55 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Functional MRI Arm
Arm Type
Experimental
Arm 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
Intervention Type
Drug
Intervention Name(s)
Tolcapone
Other Intervention Name(s)
Tasmar
Intervention Description
COMT Inhibitor
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
A pill that contains no active ingredient
Primary Outcome Measure Information:
Title
Blood Oxygen Level Dependent (BOLD) brain signal measured using functional MRI
Description
BOLD signal provides an indirect measure of brain activity during cognitive testing
Time Frame
Approximately 60-240 minutes following tolcapone/placebo administration
Title
Performance on Cognitive Testing
Description
Tasks to assess cognition will be performed while subjects are in the MRI scanner
Time Frame
Approximately 60-240 minutes following tolcapone/placebo administration

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrew S Kayser, MD PhD
Organizational Affiliation
VA Northern California Health Care System, Mather, CA
Official's Role
Principal Investigator
Facility Information:
Facility Name
VA Northern California Health Care System, Mather, CA
City
Sacramento
State/Province
California
ZIP/Postal Code
95655
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34253715
Citation
Westphal AJ, Ballard ME, Rodriguez N, Vega TA, D'Esposito M, Kayser AS. Working memory, cortical dopamine tone, and frontoparietal brain recruitment in post-traumatic stress disorder: a randomized controlled trial. Transl Psychiatry. 2021 Jul 12;11(1):389. doi: 10.1038/s41398-021-01512-6.
Results Reference
result

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Remediation of Impaired Self-Regulation in Patients With Mild TBI

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