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Regulating Homeostatic Plasticity and the Physiological Response to rTMS

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ClinicalTrials.gov Identifier: NCT03309696
Recruitment Status : Terminated (Funding issues)
First Posted : October 13, 2017
Results First Posted : November 6, 2020
Last Update Posted : November 17, 2020
Sponsor:
Information provided by (Responsible Party):
University of Arkansas

Tracking Information
First Submitted Date  ICMJE October 9, 2017
First Posted Date  ICMJE October 13, 2017
Results First Submitted Date  ICMJE October 1, 2020
Results First Posted Date  ICMJE November 6, 2020
Last Update Posted Date November 17, 2020
Actual Study Start Date  ICMJE November 16, 2017
Actual Primary Completion Date October 1, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 1, 2020)
Log Transformed P100 Amplitude of TEPs From the Global Mean Field Analysis. [ Time Frame: Up to 8 weeks ]
TEPs refer to TMS-evoked EEG potentials. The P100 amplitude of TEPs is one means of assessing cortical excitability. The P100 amplitude has been shown to be a reliable metric in studies of healthy subjects. The P100 amplitude is used in this study to assess the excitation state of two regions of interest (ROIs), one in the TC and one in the DLPFC, at each period of TEP recording (i.e., Baseline, Post tDCS, Post rTMS, and 20 minute delay).
Original Primary Outcome Measures  ICMJE
 (submitted: October 9, 2017)
Change in cortical excitability - the local mean field potential [ Time Frame: Up to 8 weeks ]
The local mean field potential of regions of interest over the temporal and frontal cortex will be measured from TMS evoked electroencephlagram (EEG) potentials (TEPs).
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Regulating Homeostatic Plasticity and the Physiological Response to rTMS
Official Title  ICMJE Regulating Homeostatic Plasticity and the Physiological Response to rTMS
Brief Summary This device-study includes a pilot, physiological investigation of normal human subjects. The aim is to determine how existing non-invasive neuromodulation devices affect brain circuitry as measured by EEG recording. Currently, the application of non-invasive neuromodulation is rarely guided by detailed knowledge of how neural activity is altered in the brain circuits that are targeted for intervention. This gap in knowledge is problematic for interpreting response variability, which is common. To address this gap, the current proposal aims to combine two forms of neuromodulation sequentially, transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), to regulate homeostatic plasticity prior to rTMS delivery at different frequencies of rTMS. Homeostatic plasticity, the initial activation state of a targeted circuit, is a key determinant of whether rTMS induces long term potentiation (LTP) or long term depression (LTD) Yet, homeostatic plasticity is rarely measured or controlled in rTMS studies. We aim to control homeostatic plasticity by preconditioning the targeted circuits with tDCS prior to rTMS delivery. The protocol included an exploratory aim to examine physiological changes in patients with tinnitus but this aim was not part of the pilot physiological investigation and it could not be completed due to funding limitations.
Detailed Description Background and Rationale: The current proposal aims to combine two forms of neuromodulation, transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), to regulate homeostatic plasticity prior to rTMS delivery at two different frequencies (1Hz and 10Hz). Homeostatic plasticity, the initial activation state of a targeted circuit, is a theoretical determinant of whether rTMS induces long term potentiation (LTP) or long term depression (LTD).Yet, homeostatic plasticity is rarely measured or controlled in rTMS studies. In a physiological investigation of health subjects, we aim to control homeostatic plasticity by preconditioning the targeted circuits with tDCS prior to rTMS delivery. The justification for this study is that controlling homeostatic plasticity can reduce subject variability and the knowledge gained can be used to optimize rTMS delivery. What is needed to move the field forward is a method for combining tDCS and rTMS and for measuring neuronal responses directly which we aim to establish in this study. The pilot study project will examine the targeted effects of neuromodulation in normal subjects. The brain regions targeted for intervention include auditory areas in the temporal cortex (TC) that process sounds and functionally connected regions of the dorsolateral frontal cortex (DLFC) that mediate sensory habituation. Due to funding limitations, only the 1 Hz rTMS condition could be initiated.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
This prospective, experimental design includes a block randomized, blinded, sham controlled, mixed effects model with sequential assignment to treatment arms (1 or 10 Hz rTMS) and random assignment to the tDCS conditions within each arm. The order of the three experimental conditions within each arm is randomized.
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Basic Science
Condition  ICMJE Tinnitus
Intervention  ICMJE
  • Device: sham tDCS and sham rTMS
    Both combinations of tDCS and rTMS in this intervention are sham.
    Other Name: transcranial direct current stimulation (tDCS), repetative transcranial magnetic stimulation (rTMS)
  • Device: sham tDCS and active rTMS
    tDCS in this intervention is sham and rTMS is active
    Other Name: transcranial direct current stimulation (tDCS), repetative transcranial magnetic stimulation (rTMS)
  • Device: active tDCS and active rTMS
    Both combinations of tDCS and rTMS in this intervention are active
    Other Name: transcranial direct current stimulation (tDCS), repetative transcranial magnetic stimulation (rTMS)
Study Arms  ICMJE
  • Experimental: tDCS and 1 Hz rTMS delivered over TC
    Participants receive sham and active 2mA tDCS over the temporal cortex (TC) prior to receiving sham and active 1 Hz rTMS (900 rTMS pulses at 110% motor threshold) delivered to the TC. .
    Interventions:
    • Device: sham tDCS and sham rTMS
    • Device: sham tDCS and active rTMS
    • Device: active tDCS and active rTMS
  • Experimental: tDCS and 10Hz rTMS delivered over TC
    Participants receive sham and active 2mA tDCS over the temporal cortex (TC) prior to receiving sham and active 10 Hz rTMS (900 rTMS pulses at 110% motor threshold) delivered to the TC.
    Interventions:
    • Device: sham tDCS and sham rTMS
    • Device: sham tDCS and active rTMS
    • Device: active tDCS and active rTMS
  • Experimental: tDCS over DLFC and 1 Hz rTMS over TC
    Participants receive sham and active 2mA tDCS over the dorsolateral frontal cortex (DLFC) prior to receiving sham and active 1 Hz rTMS (900 rTMS pulses at 110% motor threshold) delivered to the TC.
    Interventions:
    • Device: sham tDCS and sham rTMS
    • Device: sham tDCS and active rTMS
    • Device: active tDCS and active rTMS
  • Experimental: tDCS over DLFC and 10 Hz rTMS over TC
    Participants receive sham and active 2mA tDCS over the dorsolateral frontal cortex (DLFC) prior to receiving sham and active 10 Hz rTMS (900 rTMS pulses at 110% motor threshold) delivered to the TC.
    Interventions:
    • Device: sham tDCS and sham rTMS
    • Device: sham tDCS and active rTMS
    • Device: active tDCS and active rTMS
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: December 3, 2019)
10
Original Estimated Enrollment  ICMJE
 (submitted: October 9, 2017)
20
Actual Study Completion Date  ICMJE October 1, 2019
Actual Primary Completion Date October 1, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • complete the informed consent process
  • men and women, age: 21-65 years
  • negative pregnancy test (female subjects of childbearing age must take a pregnancy test).

Exclusion Criteria:

  • a personal or family history of epilepsy,
  • severe head injury, aneurysm, stroke, previous cranial neurosurgery,
  • sever or recurrent migraine headaches,
  • metal implants in the head or neck, a pacemaker,
  • pregnancy,
  • medications that lower seizure threshold,
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03309696
Other Study ID Numbers  ICMJE 206326
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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: Yes
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party University of Arkansas
Original Responsible Party Same as current
Current Study Sponsor  ICMJE University of Arkansas
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Mark Mennemeier, PhD University of Arkansas
PRS Account University of Arkansas
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP