NCT03050801

Brief Summary

Background: Traumatic brain injury (TBI) damages the connections between brain cells. This can lead to problems like memory loss. Repetitive transcranial magnetic stimulation (rTMS) can help improve connections between brain areas in healthy people. Researchers want to see if it can be useful in patients with memory problems after TBI. Objective: To see how repetitive transcranial magnetic stimulation can be used to improve the connections between parts of the brain and whether this will lead to changes in memory. Eligibility: Adults 18-50 years old with TBI who can speak and write in English. Healthy volunteers the same age and English ability. Design: Participants will be screened with a neurological exam and may have a urine pregnancy test. Participants with TBI will have 7-15 visits. Healthy volunteers will have 2-8 visits. At the visits, participants will have all or some of the following:

  • MRI for about 1 hour. Participants will lie in a machine that takes pictures in a magnetic field. Participants will do some memory tasks.
  • Memory and attention tasks with pictures and with a computer
  • Questions about their mental state and well-being
  • TMS: A wire coil is held on the scalp and a short electrical current passes through it. Participants will hear a click and feel a pulling or twitch. They may be asked to make simple movements. rTMS is repeated magnetic pulses in short bursts. They will have this for about 20 minutes. A week after the last visit, some participants will return for a memory test.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
68

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Mar 2017

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 10, 2017

Completed
3 days until next milestone

First Posted

Study publicly available on registry

February 13, 2017

Completed
1 month until next milestone

Study Start

First participant enrolled

March 24, 2017

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 10, 2020

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 7, 2020

Completed
8 months until next milestone

Results Posted

Study results publicly available

April 12, 2021

Completed
Last Updated

April 12, 2021

Status Verified

June 1, 2020

Enrollment Period

3 years

First QC Date

February 10, 2017

Results QC Date

February 11, 2021

Last Update Submit

March 15, 2021

Conditions

Keywords

Explicit MemoryImplicit MemoryMemory Disorder

Outcome Measures

Primary Outcomes (2)

  • Functional Connectivity (FC) Changes Between the Left Hippocampus and Left Parietal Cortex

    Transcranial Magnetic Stimulation (TMS) is a non-invasive technique which applies magnetic pulses to the brain via a coil inducing an electrical current in the brain. Stimulation is typically applied at sufficient intensity to trigger action potentials in nearby neurons.The motor threshold is defined as the minimum percentage of the stimulator output to elicit a motor evoked potential. Repetitive TMS (rTMS) was delivered at 100% of the motor evoked potential threshold with repeated magnetic pulses at a frequency of 20 Hz. Functional MRI (fMRI) measures the change in oxygenated blood in the brain; at rest these levels fluctuate over time. These fluctuations can be similar between different parts of the brain. FC is the similarity in fluctuations of these fMRI signals and suggest how strongly two regions communicate with each other. We measured how TMS can change FC between specific areas of the brain. A positive score suggests a stronger communication between regions of the brain.

    Changes are calculated before and the day after rTMS

  • Associative Memory Test Score Changes

    Participants studied 20 face-word pairs, and after a short delay, were required to recall the word associated with each pair. The number of correctly remembered pairs was recorded. rTMS was administered over different regions of the brain over 3 days. The Associative Memory test was administered at baseline (within a week before the first rTMS session), 1 day after the last rTMS session, and again 7-14 days after the last rTMS session. We calculated improvements on this task by subtracting the number of successfully remembered pairs 1 day after stimulation from the number remembered at baseline ("Changes one day after rTMS"). We also calculated whether these improvements lasted longer by subtracting the number of successfully remembered pairs 7-14 days after stimulation from the number remembered at baseline ("Changes 7-14 days after rTMS"). Positive scores represent increases in associative memory.

    Changes are calculated before and the day after rTMS and before and 7-14 days after rTMS

Secondary Outcomes (1)

  • Implicit Weather Prediction Task (WPT)

    Changes are calculated before and the day after rTMS, and before and 7-14 days after rTMS

Study Arms (6)

Parietal Cortex rTMS stimulation - 1 day

EXPERIMENTAL

Experiment 1

Device: rTMS

Parietal Cortex rTMS stimulation - 3 days

EXPERIMENTAL

Experiment 1

Device: rTMS

Parietal Cortex rTMS stimulation - 4 days

EXPERIMENTAL

Experiment 1

Device: rTMS

Experiment 2 - Parietal Cortex rTMS stimulation - 3 days

EXPERIMENTAL

Experiment 2

Device: rTMS

Experiment 2 - Vertex rTMS stimulation - 3 days

EXPERIMENTAL

Experiment 2

Device: rTMS

Experiment 2 - Prefrontal Cortex rTMS stimulation - 3 days

EXPERIMENTAL

Experiment 2

Device: rTMS

Interventions

rTMSDEVICE

Altering the connectivity of trans-synaptic pathways

Experiment 2 - Parietal Cortex rTMS stimulation - 3 daysExperiment 2 - Prefrontal Cortex rTMS stimulation - 3 daysExperiment 2 - Vertex rTMS stimulation - 3 daysParietal Cortex rTMS stimulation - 1 dayParietal Cortex rTMS stimulation - 3 daysParietal Cortex rTMS stimulation - 4 days

Eligibility Criteria

Age18 Years - 50 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Experiments 1 and 2:
  • Healthy individuals
  • Age 18-50 (inclusive)
  • English speaking and writing
  • Experiment 3:
  • Age 18-50 (inclusive)
  • English speaking and writing
  • History of mild to moderate TBI
  • Performance 1 standard deviation below age-adjusted population norms on the
  • CVLT-2 within the past year from the date of visit.

You may not qualify if:

  • Any current major neurological or psychiatric disorder such as (but not limited to) stroke, Parkinson disease, Alzheimer disease, schizophrenia or major depression
  • History of seizure
  • Medications acting on the central nervous system
  • Ferromagnetic metal in the cranial cavity or eye, implanted neural stimulator, cochlear implant, or ocular foreign body
  • Implanted cardiac pacemaker or auto-defibrillator or pump
  • Non-removable body piercing
  • Claustrophobia
  • Inability to lie supine for 1 hour
  • Pregnancy, nursing, or plans to become pregnant during the study.
  • Members of the NINDS Behavioral Neurology Unit (BNU)
  • For Experiment 2: Participation in Experiment 1

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

  • Wang JX, Rogers LM, Gross EZ, Ryals AJ, Dokucu ME, Brandstatt KL, Hermiller MS, Voss JL. Targeted enhancement of cortical-hippocampal brain networks and associative memory. Science. 2014 Aug 29;345(6200):1054-7. doi: 10.1126/science.1252900.

    PMID: 25170153BACKGROUND

Related Links

MeSH Terms

Conditions

Brain Injuries, TraumaticMemory Disorders

Condition Hierarchy (Ancestors)

Brain InjuriesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesCraniocerebral TraumaTrauma, Nervous SystemWounds and InjuriesNeurobehavioral ManifestationsNeurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and Symptoms

Results Point of Contact

Title
Dr. Eric Wassermann
Organization
National Institutes of Health

Study Officials

  • Eric M Wassermann, M.D.

    National Institute of Neurological Disorders and Stroke (NINDS)

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 10, 2017

First Posted

February 13, 2017

Study Start

March 24, 2017

Primary Completion

March 10, 2020

Study Completion

August 7, 2020

Last Updated

April 12, 2021

Results First Posted

April 12, 2021

Record last verified: 2020-06

Locations