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Neural Basis of Decision-Making Deficits in Traumatic Brain Injury

Primary Purpose

Traumatic Brain Injury

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

tDCS

[11C] Raclopride

About this trial

This is an interventional basic science trial for Traumatic Brain Injury focused on measuring Traumatic Brain Injury, Decision-Making, Dopaminergic Network, Brain Imaging, Non-Invasive Brain Stimulation, Natural History

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

INCLUSION CRITERIA

Inclusion Criteria for Healthy Volunteers:

Age 18 to 60
Able to give consent
Must be able to follow instructions and perform required tasks
Absence of clinically significant abnormalities during neurological examination

Inclusion Criteria for TBI:

Age 18 to 60
Able to give consent
Must be able to follow instructions and perform required tasks.
History of having a sustained, traumatically induced (e.g., collision between the head and an object, or sudden acceleration/deceleration of the brain without direct

external trauma to the head) physiological disruption of brain function, as manifested by at least one of the following (based on the American Congress of Rehabilitation Medicine Criteria):

Any period of loss of consciousness
Any loss of memory for events immediately before or after the accident
Focal neurological deficit(s) that may or may not be transient
Any alteration in mental state at the time of the accident (e.g., feeling dazed, disoriented, or confused)
Presentation to a healthcare provider within 24 hours of the injury event
History of self-reported complaints or clinical findings related to planning or decision-making deficits

EXCLUSION CRITERIA

Pre-existing and disabling major psychiatric (e.g., schizophrenia, bipolar disorder or post-traumatic stress disorder) or neurological disease (e.g., stroke, dementia, epilepsy, or multiple sclerosis).
Present use of prescribed stimulants (e.g., methylphenidate or amphetamines)
Present use of prescribed dopamine agonists/antagonists other than amantadine
For participants with childbearing capacity, pregnancy (for MRI and PET procedures) or nursing (for PET procedures only)
Contraindication to PET procedures (for PET procedures only)
Contraindication to MRI procedures as per MRI Center screening questionnaire (for MRI procedures only)
Inability to participate in at least two of the imaging procedures (PET, MRI or MEG) due to contraindications
Staff from our section
For TBI patients, history of a penetrating head wound
For healthy volunteers, history of any type of traumatically induced head injury resulting in presentation to an Emergency Department within 24 hours of the injury event

Sites / Locations

National Institutes of Health Clinical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm Description

up to 40 adult TBI patients between the ages of 18 and 60

up to 40 adult healthy volunteers between the ages of 18 and 60

Outcomes

Primary Outcome Measures

The primary objective of this protocol is to: quantify differences in performance on a decision-making task between TBI patients and healthy volunteers.

The primary outcome measure for both Experiment 1 and 2 is performance in a computerized decision-making task.

Secondary Outcome Measures

The secondary objectives of this protocol are to: determine whether baseline features of mesocorticolimbic network structure and function predict subsequent decision-making performance in both TBI patients and healthy volunteers; and determine i...

Secondary outcome measures will include quantitative estimates of structural and functional mesocorticolimbic network features, including MRI-based structural and functional connectivity, MEG-based functional dynamics, baseline dlPFC GABA concentration measured with magnetic resonance spectroscopy (MRS) imaging, dopamine D2 receptor binding potential within mesocorticolimbic subcortical nuclei measured with [11C]raclopride PET (Experiment 1). Multimodal data fusion modeling will be used to explore the predictive relationship between baseline mesocorticolimbic network states and decision-making performance within a unified state-space framework (Experiment 1), as well as the ability of these network states to predict inter-individual differences in the effects of tDCS on decision-making performance (Experiment 2).

Full Information

NCT ID

NCT02169310

First Posted

June 19, 2014

Last Updated

October 20, 2023

Sponsor

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborators

Uniformed Services University of the Health Sciences

1. Study Identification

Unique Protocol Identification Number

NCT02169310

Brief Title

Neural Basis of Decision-Making Deficits in Traumatic Brain Injury

Official Title

Neural Basis of Decision Making Deficits in Traumatic Brain Injury

Study Type

Interventional

2. Study Status

Record Verification Date

September 21, 2023

Overall Recruitment Status

Recruiting

Study Start Date

November 18, 2014 (Actual)

Primary Completion Date

December 31, 2025 (Anticipated)

Study Completion Date

December 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborators

Uniformed Services University of the Health Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

Background: People with a traumatic brain injury (TBI) can have trouble making the best possible decisions. Researchers want to learn more about the parts of the brain that control decision making. They also want to know how these are different between people. This may help predict how people make decisions after TBI. Objective: To learn more about which parts of the brain are involved in making decisions and how decisions may be hurt after TBI. Eligibility: Adults age 18 to 60. Design: Participants will be screened with medical history and physical exam. They will also take memory, attention, concentration, and thinking tests. Participants will do up to 2 experiments. For Experiment 1, participants may have 3 scans: PET: a chemical is injected through a thin tube into an arm vein. Participants lie on a bed that slides in and out of the scanner. MRI: a strong magnetic field and radio waves take pictures of the brain. Participants lie on a table that slides in and out of a metal cylinder. It makes loud knocking noises. Participants will get earplugs. They might be asked to do a task. A coil will be placed over the head. MEG: a cone with magnetic field detectors is lowered onto participants head. After the scans, participants will perform a decision-making task. For Experiment 2, participants will perform a decision-making task before and after receiving transcranial direct current stimulation (tDCS). tDCS: wet electrode sponges are placed over participants' scalp and forehead. A current passes between the electrodes. It stimulating the brain. Participants will return 24-48 hours later to repeat the decision-making task. ...

Detailed Description

Study Description: Deficits in decision-making are commonly found in individuals after traumatic brain injury (TBI) and can have a severe negative impact on quality of life. Converging evidence from both animal model and human studies suggest that decision-making deficits are linked with abnormal mesocorticolimbic network structure and function, and could potentially be mitigated through interventions that improve function within these neuronal circuits. Objectives: Quantify differences in performance on a decision-making task between TBI patients and healthy volunteers; Determine whether baseline features of mesocorticolimbic network structure and function predict subsequent decision-making performance in both TBI patients and healthy volunteers; and Determine if facilitatory transcranial direct current stimulation (tDCS) applied over the dorsolateral prefrontal cortex (dlPFC), a mesocorticolimbic network region crucially involved in decision-making, improves decision-making after TBI. Endpoints: Primary Endpoint: The primary outcome measure for both Experiment 1 and 2 is performance in a computerized decision-making task. Secondary Endpoints: Secondary outcome measures will include quantitative estimates of structural and functional mesocorticolimbic network features, including MRI-based structural and functional connectivity, MEG-based functional connectivity, baseline dlPFC GABA concentration measured with magnetic resonance spectroscopy (MRS) imaging, dopamine D2 receptor binding potential within mesocorticolimbic subcortical nuclei measured with [11C]raclopride PET (Experiment 1). Multimodal data fusion modeling will be used to explore the predictive relationship between baseline mesocorticolimbic network features and decision-making task performance within a unified state-space framework (Experiment 1), as well as the ability of these network features to predict inter-individual differences in the effects of tDCS on decision-making task performance (Experiment 2).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Traumatic Brain Injury

Keywords

Traumatic Brain Injury, Decision-Making, Dopaminergic Network, Brain Imaging, Non-Invasive Brain Stimulation, Natural History

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

up to 40 adult TBI patients between the ages of 18 and 60

Arm Title

Arm Type

Active Comparator

Arm Description

up to 40 adult healthy volunteers between the ages of 18 and 60

Intervention Type

Device

Intervention Name(s)

tDCS

Intervention Description

There is no study intervention for Experiment 1. The study intervention for Experiment 2 is tDCS. tDCS is a non-invasive brain stimulation technique that uses electrodes attached to the scalp to deliver very low intensity direct current to the brain. This intervention has been demonstrated to result in neuromodulatory effects.

Intervention Type

Drug

Intervention Name(s)

[11C] Raclopride

Intervention Description

[11C] Raclopride is administered under an IND 054135. This IND is sponsored by the NIH Clinical Center and [11C] Raclopride is dispensed by the NIH PET Department. Quality Assurance for Radioactive Drug: [11C] Raclopride, is assayed for radiochemical purity under the supervision of the NIH PET Department prior to dispensing the drug for administration. Given that IND PET drugs manufactured at the NIH PET Department are used in a single site and that there is no intent for their commercialization, submission of IBs has not been required by FDA for any of the NIH Office of Research Support and Compliance-sponsored IND applications.

Primary Outcome Measure Information:

Title

The primary objective of this protocol is to: quantify differences in performance on a decision-making task between TBI patients and healthy volunteers.

Description

The primary outcome measure for both Experiment 1 and 2 is performance in a computerized decision-making task.

Time Frame

Participation may be completed over the course of a week, or longer depending on participant s schedule and testing availability. Typically, individuals complete the full study with 4-7 days.

Secondary Outcome Measure Information:

Title

Description

Time Frame

Participation may be completed over the course of a week, or longer depending on participant s schedule and testing availability. Typically, individuals complete the full study with 4-7 days.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

INCLUSION CRITERIA Inclusion Criteria for Healthy Volunteers: Age 18 to 60 Able to give consent Must be able to follow instructions and perform required tasks Absence of clinically significant abnormalities during neurological examination Inclusion Criteria for TBI: Age 18 to 60 Able to give consent Must be able to follow instructions and perform required tasks. History of having a sustained, traumatically induced (e.g., collision between the head and an object, or sudden acceleration/deceleration of the brain without direct external trauma to the head) physiological disruption of brain function, as manifested by at least one of the following (based on the American Congress of Rehabilitation Medicine Criteria): Any period of loss of consciousness Any loss of memory for events immediately before or after the accident Focal neurological deficit(s) that may or may not be transient Any alteration in mental state at the time of the accident (e.g., feeling dazed, disoriented, or confused) Presentation to a healthcare provider within 24 hours of the injury event History of self-reported complaints or clinical findings related to planning or decision-making deficits EXCLUSION CRITERIA Pre-existing and disabling major psychiatric (e.g., schizophrenia, bipolar disorder or post-traumatic stress disorder) or neurological disease (e.g., stroke, dementia, epilepsy, or multiple sclerosis). Present use of prescribed stimulants (e.g., methylphenidate or amphetamines) Present use of prescribed dopamine agonists/antagonists other than amantadine For participants with childbearing capacity, pregnancy (for MRI and PET procedures) or nursing (for PET procedures only) Contraindication to PET procedures (for PET procedures only) Contraindication to MRI procedures as per MRI Center screening questionnaire (for MRI procedures only) Inability to participate in at least two of the imaging procedures (PET, MRI or MEG) due to contraindications Staff from our section For TBI patients, history of a penetrating head wound For healthy volunteers, history of any type of traumatically induced head injury resulting in presentation to an Emergency Department within 24 hours of the injury event

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Tasneem F Malik, C.R.N.P.

Phone

(301) 451-1335

tasneem.malik@nih.gov

First Name & Middle Initial & Last Name or Official Title & Degree

Leonardo G Cohen, M.D.

Phone

(301) 496-9782

cohenl1@mail.nih.gov

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Leonardo G Cohen, M.D.

Organizational Affiliation

National Institute of Neurological Disorders and Stroke (NINDS)

Official's Role

Principal Investigator

Facility Information:

Facility Name

National Institutes of Health Clinical Center

City

Bethesda

State/Province

Maryland

ZIP/Postal Code

20892

Country

United States

Individual Site Status

Recruiting

12. IPD Sharing Statement

Links:

URL

https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2014-N-0083.html

Description

NIH Clinical Center Detailed Web Page

Learn more about this trial

Neural Basis of Decision-Making Deficits in Traumatic Brain Injury

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