Mechanisms of Non-Invasive Neuromodulation Interventions: Influence on Human Neurochemistry and Functional Connectivity

November 4, 2019 updated by: University of Minnesota
The aim of this project is to increase our understanding of how two different protocols of repetitive transcranial magnetic stimulation (rTMS), inhibitory (1 Hz) and excitatory (5 Hz), applied over the primary motor cortex of the presumed dominant hemisphere, affect functional connectivity and neurochemistry in the brain.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation method which is effective for treating both psychiatric and non-psychiatric disorders, such as posttraumatic stress disorder, obsessive compulsive disorder, pain syndromes and for improving motor function in neurodegenerative diseases or following stroke. rTMS uses series of brief pulses of magnetic field applied to the surface of the head for a period of time (e.g. 20 minutes). The effects of rTMS are transient, and critically dependent upon the location, frequency and intensity of stimulation. Several studies have provided evidence that rTMS can influence the excitability and function of neurons (neuromodulation) for up to one hour, both near to, and distant from, the site of stimulation. However it is still unclear how these transient local and distant changes in function induced by specific rTMS protocols are mediated. In this project we will combine expertise in Magnetic Resonance Imaging (MRI), Magnetic Resonance Spectroscopy (MRS) and rTMS neuromodulation to develop and test protocols for examining the changes produced by non-invasive brain stimulation on healthy subjects. rTMS will be applied outside the scanner using standard TMS coils and MRI/S at 7 Tesla will be acquired before and immediately after rTMS. Our aim is to increase the understanding of how the two different rTMS protocols, inhibitory (1 Hz) and excitatory (5 Hz), applied over the primary motor cortex of the presumed dominant hemisphere, affect functional connectivity and neurochemistry in the brain.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
8

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Center for Magnetic Resonance Research, Dept. of Radiology, University of Minnesota

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

21 years to 40 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion Criteria:

Those volunteers who are evaluated as normal and not met exclusion criteria will be potential candidates for this study.

Exclusion Criteria:

The following participants will be excluded from this study, including but not limited to:

  • Females
  • Left handed males
  • Participants who never underwent MRI at 7 Tesla

Participants with:

  • any type of bio-implant activated by mechanical, electronic, or magnetic means (e.g. cochlear implants, pacemakers, neurostimulators, bio stimulators, electronic infusion pumps.)
  • any type of ferromagnetic bio-implant that could potentially be displaced or damaged, such as aneurysm clips, metallic skull plates, etc.
  • non-removable piercing or permanent eyeliner
  • retained metal in their body, either from a medical procedure or an injury

Participants who:

  • have been diagnosed by a physician as having a psychiatric disorder, substance abuse, neurological and/or cardiovascular disease
  • have cardiac or known circulatory impairment, and/or the inability to perspire (poor thermoregulatory function)
  • have hyper- or hypotension or arrhythmias
  • have known conditions which can lead to emergency medical care
  • had a head injury that caused them to lose consciousness for more than 30 minutes or have amnesia for more than 24 hours
  • had a brain tumor or stroke
  • had one or more seizures, or been given a diagnosis of epilepsy
  • have a history of sleep apnea or head trauma that may have caused Traumatic Brain Injury (TBI)
  • have a history of anxiety, syncope, panic attacks and/or claustrophobia
  • cannot adhere to the experimental protocol for any reason
  • started taking chemotherapy or immunomodulatory agents, or had any radiation treatment that could affect the brain
  • are currently on any medication

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Inhibitory rTMS (1 Hz)
Subjects are exposed to a 20-min inhibitory rTMS intervention that transiently suppresses the excitability of cortical structures beneath the site of stimulation. Subjects undergo MRI and MRS both before and right after the rTMS intervention.
Device: Inhibitory rTMS (1 Hz)
Participants receive rTMS at a rate of 1 Hz, applied with a 70-mm figure-eight TMS coil connected to a stimulator, over the motor cortex hotspot contralateral to the dominant arm for 20 minutes at an intensity of 90% resting motor threshold (RMT) for a total of 600 TMS pulses. The total number of stimuli applied is well within the published safety guidelines for use of rTMS. rTMS is applied outside the scanner, whereas functional connectivity and neurochemistry are measured with MRI and MRS, respectively, at 7 Tesla. The MRI/MRS data are collected right before and immediately after the inhibitory rTMS intervention.
Experimental: Excitatory rTMS (5 Hz)
Subjects are exposed to a 20-min excitatory rTMS intervention that transiently increases the net excitability of cortical structures beneath the site of stimulation. Subjects undergo MRI and MRS both before and right after the rTMS intervention.
Device: Excitatory rTMS (5 Hz)
Participants receive rTMS at a rate of 5 Hz, applied with a 70-mm figure-eight TMS coil connected to a stimulator, over the motor cortex hotspot contralateral to the dominant arm for 20 minutes at an intensity of 90% RMT for a total of 600 TMS pulses. The total number of stimuli applied is well within the published safety guidelines for use of rTMS. rTMS is applied outside the scanner, whereas functional connectivity and neurochemistry are measured with MRI and MRS, respectively, at 7 Tesla. The MRI/MRS data are collected right before and immediately after the excitatory rTMS intervention.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percent Change of GABA Concentration in a Voxel Encompassing the Left Motor Cortex, Measured at 30 Min After rTMS
Time Frame: Baseline/Pre-rTMS and 30 min after rTMS
GABA concentration is quantified with MRS at 7 Tesla. Percent change of GABA concentration is calculated from baseline (i.e., pre-rTMS).
Baseline/Pre-rTMS and 30 min after rTMS
Percent Change of GABA Concentration in a Voxel Encompassing the Right Motor Cortex, Measured at 60 Min After rTMS
Time Frame: Baseline/Pre-rTMS and 60 min after rTMS
GABA concentration is quantified with MRS at 7 Tesla. Percent change of GABA concentration is calculated from baseline (i.e., pre-rTMS).
Baseline/Pre-rTMS and 60 min after rTMS
Percent Change of Functional Connectivity in Left Motor Cortex, Where Functional Connectivity is Measured as a Dimensionless Fractional Amplitude of Low-frequency Fluctuations (fALFF), at 80 Min After rTMS
Time Frame: Baseline/Pre-rTMS and 80 min after rTMS
Functional connectivity is measured with MRI at 7 Tesla as a dimensionless fractional amplitude of low-frequency fluctuations (fALFF). This is an index which reflects the intensity of spontaneous regional brain activity. It is calculated as the ratio of power spectra of low frequency (0.01-0.08 Hz) to that of the entire frequency range. Percent change of functional connectivity is calculated from baseline (i.e., pre-rTMS).
Baseline/Pre-rTMS and 80 min after rTMS
Percent Change of Functional Connectivity in Right Motor Cortex, Where Functional Connectivity is Measured as a Dimensionless Fractional Amplitude of Low-frequency Fluctuations (fALFF), at 80 Min After rTMS
Time Frame: Baseline/Pre-rTMS and 80 min after rTMS
Functional connectivity is measured with MRI at 7 Tesla as a dimensionless fractional amplitude of low-frequency fluctuations (fALFF). This is an index which reflects the intensity of spontaneous regional brain activity. It is calculated as the ratio of power spectra of low frequency (0.01-0.08 Hz) to that of the entire frequency range. Percent change of functional connectivity is calculated from baseline (i.e., pre-rTMS).
Baseline/Pre-rTMS and 80 min after rTMS

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Minnesota

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Silvia Mangia, PhD, Dept. of Radiology, University of Minnesota

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 29, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 19, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 19, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 2, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 4, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 9, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 18, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 4, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2019

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1601M83405

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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