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Probing Cortical Excitability and Cognitive Function With TMS

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ClinicalTrials.gov Identifier: NCT03652012
Recruitment Status : Recruiting
First Posted : August 29, 2018
Last Update Posted : November 1, 2018
Sponsor:
Information provided by (Responsible Party):
Ying-hui Chou, University of Arizona

Brief Summary:

The overarching purpose of this study is to develop a technique that is capable of identifying neurophysiological biomarkers sensitive enough to detect preclinical dementia by integrating Transcranial Magnetic Stimulation (TMS) and Functional Magnetic Resonance Imaging (fMRI). More specifically, this project has two specific aims:

  • 1. To characterize cortical excitability and its relation to cognitive function using single-pulse TMS paradigm in Mild Cognitive Impairment (MCI) and healthy older adults.
  • 2. To delineate cortical plasticity and its association to cognitive function using repetitive TMS paradigm and resting-state fMRI in MCI and healthy older adults.

Techniques to artificially and precisely stimulate brain tissue are increasingly recognized as valuable tools both in clinical practice and in cognitive neuroscience studies among healthy individuals. Transcranial magnetic stimulation (TMS) is a non-invasive approach to stimulate the brain. Importantly, unlike other invasive brain stimulation techniques (e.g., surgical deep brain stimulation), no surgery, anesthesia, or sedation is involved. Instead, TMS involves placing a magnetic coil on the surface of the head. This coil then generates a magnetic field that is about the same strength as the magnetic field used by MRI machines, and when this magnetic field rapidly alternates, the neurons under the coil are excited.

Extensive guidelines have been published by experts in the field to ensure safe use, and the thousands of patients & research participants who have received TMS in compliance with these guidelines demonstrate the safety of this practice. Depending on the method of use, TMS is very versatile -- it can be used to study research questions pertaining to the neural circuitry of the brain, it can be used as a diagnostic device, and it can be used therapeutically to treat various neurological conditions.

In this study, the investigators intend to further study the potential for diagnostic applications of TMS. More specifically, TMS and brain imaging techniques will be used in combination in order to more sensitively diagnose dementia - perhaps even before symptoms emerge. Right now, there is no reliable method for doing so and it is difficult to distinguish between the forgetfulness of healthy aging and the early signs of disease. Our approach may provide a more sensitive diagnostic tool, which is likely to improve clinical outcomes.


Condition or disease Intervention/treatment Phase
Cognitive Dysfunction Device: Transcranial Magnetic Stimulation (TMS) Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Probing Cortical Excitability and Cognitive Function in Mild Cognitive Impairment With Transcranial Magnetic Stimulation
Actual Study Start Date : April 3, 2018
Estimated Primary Completion Date : October 31, 2019
Estimated Study Completion Date : October 31, 2019

Arm Intervention/treatment
Experimental: Mild Cognitive Impairment

The following revised Mayo Clinic criteria for MCI (Petersen, et al. 2014) will be used: (1) cognitive concern expressed by a physician, informant, participant, or nurse; (2) impairment in 1 or more cognitive domains (memory, language, visuospatial skills, or executive functions); (3) essentially normal functional activities; and (4) absence of dementia. Individuals with MCI will have Mini-Mental State Exam (MMSE, Appendix 19) scores between 18 and 23 (inclusive) and have a Clinical Dementia Rating Scale score of 0.5.

This group will undergo Transcranial Magnetic Stimulation (TMS) protocol.

Device: Transcranial Magnetic Stimulation (TMS)
TMS in a non-invasive brain stimulation technique. In this study, we will use TMS to excite brain tissue in the motor cortex and measure the subsequent motor response in the hand. This 'intervention' will be the same in both cohorts, as we are interested in how this motor response to TMS may vary across two distinct cohorts.

Active Comparator: Healthy Controls

Participants who are matched for age and gender.

This group will undergo Transcranial Magnetic Stimulation (TMS) protocol.

Device: Transcranial Magnetic Stimulation (TMS)
TMS in a non-invasive brain stimulation technique. In this study, we will use TMS to excite brain tissue in the motor cortex and measure the subsequent motor response in the hand. This 'intervention' will be the same in both cohorts, as we are interested in how this motor response to TMS may vary across two distinct cohorts.




Primary Outcome Measures :
  1. Cortical Excitability: Resting Motor Threshold (RMT). Measured with EMG, Resting Motor Threshold is the minimum amount of stimulation intensity over the motor hotspot that elicits a motor evoked response. [ Time Frame: Up to 10 minutes. This is a single day trial. Testing session will last a total of 3 hours. ]
    Measured with surface EMG during single-pulse TMS paradigm. Resting Motor Threshold is the minimum amount of stimulation intensity over the motor hotspot that elicits a motor evoked response.


Secondary Outcome Measures :
  1. Cortical Excitability: Stimulus Response Curve. Measured with EMG, this measures motor response to various intensities of magnetic pulse stimuli [ Time Frame: Up to 30 minutes. This is a single day trial. Testing session will last a total of 3 hours. ]
    Measured with surface EMG during single-pulse TMS paradigm. The outcome measure is derived from the varying Motor-Evoked Response potentials that are induced by variable TMS stimulation intensities.

  2. Cortical Excitability: Cortical Silent Period. Measured with EMG, this is a direct measure of cortical inhibition. [ Time Frame: Up to 10 minutes. This is a single day trial. Testing session will last a total of 3 hours. ]
    Measured with surface EMG during single-pulse TMS paradigm. Participants will be asked to voluntary contract hand muscle, at 20% of their maximum contraction force. A TMS pulse is applied while participants are applying this voluntary contraction. The cortical silent period is defined as the duration between the observed motor evoked potential and the resumption of muscle voluntary contraction.

  3. Baseline Functional Magnetic Resonance Imaging (fMRI) to observe functional activation of brain networks prior to intervention. [ Time Frame: Up to 30 minutes. This is a single day trial. Testing session will last a total of 3 hours. ]
    This will be a resting state fMRI scan to measure functional connectivity patterns prior to non-invasive brain stimulation protocol.

  4. Post Functional Magnetic Resonance Imaging (fMRI) to observe functional activation of brain networks immediately following intervention. [ Time Frame: Up to 30 minutes. This is a single day trial. Testing session will last a total of 3 hours. ]
    This will be a resting state fMRI scan to measure functional connectivity patterns immediately following non-invasive brain stimulation protocol.



Information from the National Library of Medicine

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Ages Eligible for Study:   60 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • The following revised Mayo Clinic criteria for MCI will be used: (1) cognitive concern expressed by a physician, informant, participant, or nurse; (2) impairment in 1 or more cognitive domains (memory, language, visuospatial skills, or executive functions); (3) essentially normal functional activities; and (4) absence of dementia. Individuals with MCI will have Mini-Mental State Exam (MMSE, Appendix 19) scores between 18 and 23 (inclusive) and have a Clinical Dementia Rating Scale score of 0.5.
  • Health controls will be screened with MMSE

Exclusion Criteria:

  • Contraindications to MRI
  • Contraindications to TMS
  • history of stroke
  • clinical diagnosis of dementia
  • diagnosis of neuropsychiatric disorder
  • left handed

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03652012


Contacts
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Contact: Mark H Sundman, MS 520-626-7755 marksundman@email.arizona.edu
Contact: Ying-hui Chou, Sc.D. yinghuichou@email.arizona.edu

Locations
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United States, Arizona
University of Arizona Recruiting
Tucson, Arizona, United States, 85721
Contact: Mark Sundman, MS       marksundman@email.arizona.edu   
Contact: Ying-hui Chou, Sc.D       yinghuichou@email.arizona.edu   
Sponsors and Collaborators
University of Arizona

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Responsible Party: Ying-hui Chou, Assistant Professor of Psychology, Cognition and Neural Systems Program, University of Arizona
ClinicalTrials.gov Identifier: NCT03652012     History of Changes
Other Study ID Numbers: 1707654427
First Posted: August 29, 2018    Key Record Dates
Last Update Posted: November 1, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Keywords provided by Ying-hui Chou, University of Arizona:
Mild Cognitive Impairment
Additional relevant MeSH terms:
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Cognitive Dysfunction
Cognition Disorders
Neurocognitive Disorders
Mental Disorders