Clinical trial NCT02260570: 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
Overall status: COMPLETED
Phase: NA
Conditions: Mild Traumatic Brain Injury
Keywords: concussion
traumatic brain injury
MRI
memory
tolcapone
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
Collaborators: name: University of California, Berkeley
name: University of California, San Francisco
First posted: 2014-10-09
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Blood Oxygen Level Dependent (BOLD) brain signal measured using functional MRI
timeFrame: Approximately 60-240 minutes following tolcapone/placebo administration
measure: Performance on Cognitive Testing
timeFrame: Approximately 60-240 minutes following tolcapone/placebo administration
Secondary outcomes:
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: VA Northern California Health Care System, Mather, CA
state: California
Study officials:
affiliation: VA Northern California Health Care System, Mather, CA
name: Andrew S Kayser, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.