NCT02465034

Brief Summary

The purpose of this study is to examine how different areas in the brain interact with each other and how using brain imaging and brain stimulation approaches can influence these interactions.

Trial Health

57
Monitor

Trial Health Score

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

Enrollment
45

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started May 2015

Longer than P75 for not_applicable

Geographic Reach
1 country

2 active sites

Status
terminated

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

Study Start

First participant enrolled

May 1, 2015

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

June 3, 2015

Completed
5 days until next milestone

First Posted

Study publicly available on registry

June 8, 2015

Completed
4.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 24, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 24, 2019

Completed
2.3 years until next milestone

Results Posted

Study results publicly available

November 26, 2021

Completed
Last Updated

November 26, 2021

Status Verified

October 1, 2021

Enrollment Period

4.2 years

First QC Date

June 3, 2015

Results QC Date

October 29, 2021

Last Update Submit

October 29, 2021

Conditions

Cerebrovascular Stroke

Keywords

Neural plasticityNoninvasive brain stimulationMotor cortex

Outcome Measures

Primary Outcomes (3)

  • Change in Long-term Potentiation-like Plasticity

    Long-term potentiation-like plasticity was measured using paired associative stimulation (PAS). PAS consists of repeated peripheral electric stimulation paired with Transcranial Magnetic Stimulation (TMS) applied to the motor cortex at varying interstimulus intervals. Participants received 180 paired stimuli at 0.25 hertz (Hz) for 12 minutes. Impaired long-term potentiation-like plasticity points towards reduced excitatory synaptic connectivity and deficits in sensorimotor integration. Decrease or no change in the amplitudes of motor-evoked potentials (MEPs) indicates impaired long-term potentiation-like plasticity.

    Baseline, 1 Minute Post-Paired Associative Stimulation

  • Electroencephalography Recordings at Baseline and 5 MInutes Post-PAS

    Electroencephalography (EEG) data were recorded using a 64-channel TMS-compatible electrode cap (Easy Cap). Signals were collected at 2000 hertz (Hz) during pre- and post-transcranial magnetic stimulation epochs (-100ms to 200ms). Up to fifty suprathreshold (120% AMT) transcranial magnetic stimulation pulses were applied to motor cortex while the subject was seated quietly with eyes open. This procedure was conducted bilaterally. Data epochs (-1000 to 4000 ms with respect to TMS delivery) were extracted for subsequent imaginary phase coherence analysis. Post-TMS coherence values between electrodes overlying M1 bilaterally (C3 and C4) were calculated within the beta frequency range (15 to 30 Hz). EEG data values are unit-free that can range from 0 to 1. Higher values represent greater coherence which is thought to indicate stronger connectivity.

    Baseline, 5 Minutes Post-Paired Associative Stimulation

  • Abbreviated Wolf Motor Function Test Time

    Three items of the Wolf Motor Function Test (WMFT) were used to evaluate functional motor performance. The 3 items were selected based on task difficulty ranging from easiest (hand to table) to most difficult (stack checkers) along with a task of moderate difficulty (lift can). Each task has different control demands and number of actions required to complete successfully. Task performance is timed in seconds, with a maximum time of 120 seconds.

    Baseline, 10 Minutes Post-Paired Associative Stimulation

Secondary Outcomes (5)

  • Wolf Motor Function Test

    Baseline

  • Abbreviated Wolf Motor Function Test Time

    30 minutes post-Paired Associative Stimulation, 24 hours post-Paired Associative Stimulation

  • Long-term Potentiation-like Plasticity

    30 minutes post-Paired Associative Stimulation, 24 hours post-Paired Associative Stimulation

  • Electroencephalography Recordings at 30 Minutes and 24 Hours Post-PAS

    30 minutes post-Paired Associative Stimulation, 24 hours post-Paired Associative Stimulation

  • Serial Reaction Time Task (SRTT) Performance

    Baseline, 10 minutes post-PAS, 30 minutes post-PAS, and 24 hours post-PAS

Study Arms (2)

Subcortical stroke

ACTIVE COMPARATOR

Subjects with subcortical stroke in the chronic phase of recovery with mild-moderate impairment of arm function will undergo noninvasive targeting of cortical locations by stereotactic neuronavigation using Transcranial Magnetic Stimulation (TMS), median nerve stimulation and arm motor function assessments. A paired associative stimulation (PAS) protocol using noninvasive stimulation will also be used which will be one of the following, a traditional or a corticocortical or a sham paired associative stimulation protocol. The subjects will also undergo median nerve stimulation.

Device: Transcranial Magnetic StimulationDevice: Traditional Paired Associative StimulationDevice: Median Nerve StimulationDevice: Corticocortical Paired Associative StimulationDevice: Sham Paired Associative Stimulation

Healthy Control

ACTIVE COMPARATOR

Healthy individuals will undergo noninvasive targeting of cortical locations by stereotactic neuronavigation using Transcranial Magnetic Stimulation (TMS), median nerve stimulation and arm motor function assessments. A paired associative stimulation (PAS) protocol using noninvasive stimulation will also be used which will be one of the following, a traditional or a corticocortical or a sham paired associative stimulation protocol.

Device: Transcranial Magnetic StimulationDevice: Traditional Paired Associative StimulationDevice: Median Nerve StimulationDevice: Corticocortical Paired Associative StimulationDevice: Sham Paired Associative Stimulation

Interventions

Transcranial Magnetic StimulationDEVICE

Transcranial Magnetic Stimulation (TMS) will be performed using the Magstim BiStim\^2 paired pulse stimulator to measure transient cortical excitability. Single pulse transcranial magnetic stimulation applied at low frequencies (not greater than 0.25 hertz (Hz)) will be used. The may be repeated at multiple study visits. All five study visits will be completed within four weeks of the initial visit.

Also known as: Magstim BiStim^2
Healthy ControlSubcortical stroke
Traditional Paired Associative StimulationDEVICE

Paired associative stimulation (PAS) is a combination of transcranial magnetic stimulation (TMS) and electrical stimulation of the median nerve. 180 paired stimuli are delivered at 0.25 Hz for 12 minutes. Median nerve stimuli at 300% of the perceptual threshold will be applied 25ms prior to transcranial magnetic stimulation delivery over the ipsilesional (stroke) or non-dominant (control) cortex. Transcranial Magnetic Stimulation (TMS) will be performed using the Magstim BiStim\^2 paired pulse stimulator unit and a bipolar bar electrode will be used for median nerve stimulation. This traditional paired associative stimulation may be repeated at multiple study visits. All five study visits will be completed within four weeks of the initial visit.

Also known as: Magstim BiStim^2
Healthy ControlSubcortical stroke
Median Nerve StimulationDEVICE

Stimulation of the median nerve will be performed using a bipolar bar electrode affixed to palmar aspect of the forearm proximal to the crease of the wrist bilaterally. Stimuli will be delivered 23ms prior to the transcranial magnetic stimulation (TMS) pulse with 0.1 milliseconds (ms) rectangular pulses at an intensity to evoke a 1 millivolt (mV) response in the abductor pollicis brevis (APB) muscle. This may may be repeated at multiple study visits. All five study visits will be completed within four weeks of the initial visit.

Healthy ControlSubcortical stroke
Corticocortical Paired Associative StimulationDEVICE

Cortico-cortical Paired Associative Stimulation (CC-PAS) is a combination of TMS and electrical stimulation of the median nerve. 180 paired stimuli are delivered at 0.25 Hz for 12 minutes. The interstimulus interval will range from 5-15 ms depending on site of stimulation.TMS will be performed using the Magstim BiStim\^2 paired pulse stimulator unit and a bipolar bar electrode will be used for median nerve stimulation. This CC-PAS may be repeated at multiple study visits. All five study visits will be completed within four weeks of the initial visit.

Also known as: Magstim BiStim^2
Healthy ControlSubcortical stroke
Sham Paired Associative StimulationDEVICE

The sham PAS is a combination of TMS and electrical stimulation of the median nerve. The coil is rotated and separated from the head with a plastic spacer to ensure indirect contact with the head.180 paired stimuli are delivered at 0.25 Hz for 12 minutes. TMS will be performed using the Magstim BiStim\^2 paired pulse stimulator unit and a bipolar bar electrode will be used for median nerve stimulation. This sham paired associative stimulation may be repeated at multiple study visits. All five study visits will be completed within four weeks of the initial visit.

Also known as: Magstim BiStim^2
Healthy ControlSubcortical stroke

Eligibility Criteria

Age18 Years - 85 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age between 18-85 years
  • Middle cerebral artery stroke
  • Individuals with a first time stroke that affects the corona radiata and/or internal capsule

You may not qualify if:

  • Age outside the age range of 18-85 years
  • Signs of dementia (score \< 24 on the Montreal Cognitive Assessment)
  • Aphasia (score \< 13 on the Frenchay Aphasia Screen)
  • History of head trauma
  • History of a major psychiatric diagnosis
  • History of a neurodegenerative disorder
  • History of substance abuse
  • Contraindications to Transcranial Magnetic Stimulation

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Emory University

Atlanta, Georgia, 30322, United States

Location

Wesley Woods Center

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

  • Borich MR, Wolf SL, Tan AQ, Palmer JA. Targeted Neuromodulation of Abnormal Interhemispheric Connectivity to Promote Neural Plasticity and Recovery of Arm Function after Stroke: A Randomized Crossover Clinical Trial Study Protocol. Neural Plast. 2018 Mar 12;2018:9875326. doi: 10.1155/2018/9875326. eCollection 2018.

    PMID: 29721010DERIVED

MeSH Terms

Conditions

Stroke

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Cerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

Magnetic Field TherapyTherapeutics

Results Point of Contact

Title
Dr. Michael Borich
Organization
Emory University
michael.borich@emory.edu
404-712-0612

Study Officials

  • Michael Borich, DPT, PhD

    Emory University

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor

Study Record Dates

First Submitted

June 3, 2015

First Posted

June 8, 2015

Study Start

May 1, 2015

Primary Completion

July 24, 2019

Study Completion

July 24, 2019

Last Updated

November 26, 2021

Results First Posted

November 26, 2021

Record last verified: 2021-10

Data Sharing

IPD Sharing
Will not share

Locations

US(2)