Functional Connectivity as a Biomarker of rTMS

Traumatic Brain Injury Clinical Trial

Official title:

Functional Connectivity as a Biomarker of rTMS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03050801
• Other study ID #: 170055
• Secondary ID: 17-N-0055
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 24, 2017
• Est. completion date: August 7, 2020

Study information

• Verified date: June 2020
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Objective: To use resting state functional connectivity (FC) as a biomarker of synaptic modulation by repetitive transcranial magnetic stimulation (rTMS) in paradigms intended to improve memory and learning. Ancillary outcomes include the effects of rTMS on the interaction between the explicit implicit memory systems.

Study population: Healthy adult volunteers

Design: The study contains two experiments. Experiment 1 is designed to establish the number of rTMS sessions required to produce a meaningful change in resting parieto-hippocampal FC in healthy subjects. Experiment 2 will replicate a prior experiment which used rTMS to enhance the explicit memory system in healthy subjects, and look for potential effects on the implicit system. This intervention will be contrasted with a negative control condition (vertex stimulation) in a between-groups design.

Outcome measures: The primary outcome measure is the change in FC produced by serially applied rTMS and improvement in explicit memory. We will explore whether enhancement of the explicit system has effects on resting state connectivity in the implicit system and whether white matter integrity predicts changes in FC in healthy subjects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: August 7, 2020
• Est. primary completion date: March 10, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

INCLUSION CRITERIA:

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.

EXCLUSION CRITERIA:

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

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Traumatic Brain Injury

Intervention

Device:
• rTMS
Altering the connectivity of trans-synaptic pathways

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Implicit Weather Prediction Task (WPT)	Participants learn implicit, probabilistic relationships between stimuli and responses through feedback. 1, 2 and 3 card combinations of 4 possible cards are presented on a computer; the subject is asked to predict whether it will be rainy or fine. After each prediction, the subject receives corrective feedback. Each card is independently associated with one outcome with a fixed probability.The WPT was administered at baseline and 1 day after and 7-14 days after the last rTMS session. Scores at each time point represent the proportion of responses associated with a reward (optimal responses). We calculated improvement by subtracting the number of optimal responses 1 day after stimulation from the number at baseline (Changes one day after rTMS). We also calculated if these improvements lasted longer by subtracting the number of optimal responses 7-14 days after stimulation from the number at baseline (Changes 7-14 days after rTMS).Positive scores represent increases in implicit memory.	Changes are calculated before and the day after rTMS, and before and 7-14 days after rTMS

External Links

•   NIH Clinical Center Detailed Web Page