Regulating Homeostatic Plasticity and the Physiological Response to rTMS

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

Tracking Information

• First Submitted Date: October 9, 2017
• First Posted Date: October 13, 2017
• Results First Submitted Date: October 1, 2020
• Results First Posted Date: November 6, 2020
• Last Update Posted Date: November 17, 2020
• Actual Study Start Date: November 16, 2017
• Actual Primary Completion Date: October 1, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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).

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Regulating Homeostatic Plasticity and the Physiological Response to rTMS
• Official Title: 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: Interventional
• Study Phase: Not Applicable

Study Design

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: Tinnitus

Intervention

• 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

• 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

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: December 3, 2019): 10
• Original Estimated Enrollment (submitted: October 9, 2017): 20
• Actual Study Completion Date: October 1, 2019
• Actual Primary Completion Date: October 1, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 21 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03309696
• Other Study ID Numbers: 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: Not Provided
• Current Responsible Party: University of Arkansas
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Arkansas
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Mark Mennemeier, PhD; University of Arkansas

• PRS Account: University of Arkansas
• Verification Date: November 2020