CClinicalTrials.gg
TerminatedNCT03309696Updated Nov 17, 2020Results posted

Regulating Homeostatic Plasticity and the Physiological Response to rTMS

An interventional study of sham tDCS and sham rTMS and sham tDCS and active rTMS in Tinnitus, sponsored by University of Arkansas. Terminated at 1 site in United States. Open to participants aged 21 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-11-17.

Sponsored by University of Arkansas · Not applicable, Interventional, and Basic science

Why this study was terminated
Funding issues
Phase
Not applicable
Study type
Interventional
Enrollment
10
Allocation
Randomized
Ages
21 Years to 65 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Tinnitus

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03

Who can participate

Ages eligible
21 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

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

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,
04

Study design

Phase
Not applicable
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Outcomes assessor)
Enrollment
10 participants (actual)

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. .

    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.

    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.

    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.

    Device: sham tDCS and sham rTMS · Device: sham tDCS and active rTMS · Device: active tDCS and active rTMS

Interventions

  • Devicesham tDCS and sham rTMS

    Both combinations of tDCS and rTMS in this intervention are sham.

    Also known as: transcranial direct current stimulation (tDCS), repetative transcranial magnetic stimulation (rTMS)

  • Devicesham tDCS and active rTMS

    tDCS in this intervention is sham and rTMS is active

    Also known as: transcranial direct current stimulation (tDCS), repetative transcranial magnetic stimulation (rTMS)

  • Deviceactive tDCS and active rTMS

    Both combinations of tDCS and rTMS in this intervention are active

    Also known as: transcranial direct current stimulation (tDCS), repetative transcranial magnetic stimulation (rTMS)

05

What researchers measure

Primary outcomes

  1. Log Transformed P100 Amplitude of TEPs From the Global Mean Field Analysis.

    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).

    Time frame: Up to 8 weeks

06

Results

Posted Nov 6, 2020
Limitations and caveats
Our pilot study funding ended. Subjects could not be recruited for the 10 Hz rTMS arm. A proposed study of tinnitus patients could not be initiated. Data analysis could only be completed for one arm.

Participant flow

Participant flow — Overall Study
MilestonetDCS and 1 Hz rTMS Delivered Over TCtDCS Over DLFC and 1 Hz rTMS Over TCtDCS and 10Hz rTMS Delivered Over TCtDCS Over DLFC and 10 Hz rTMS Over TC
Started5500
Completed5000
Not completed0500
Withdrew: Analysis of tep data could not be completed0500

Outcome measures

PrimaryLog Transformed P100 Amplitude of TEPs From the Global Mean Field Analysis.

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).

Time frame:
Up to 8 weeks
Reported as:
Mean · log µV
Log Transformed P100 Amplitude of TEPs From the Global Mean Field Analysis.
log µVSham tDCS PreconditioningActive tDCS PreconditioningSham tDCS Preconditioning of Sham rTMSSham tDCS Preconditioning of Active rTMSActive tDCS Preconditioning of Active rTMS
Log Transformed P100 Amplitude of TEPs From the Global Mean Field Analysis.1.85 ± 0.711.26 ± 0.331.59 ± 0.821.30 ± 0.581.11 ± 0.48
Statistical analysis
  • Sham tDCS Preconditioning vs Active tDCS Preconditioning · Mixed Models Analysis · p = .055 (The p value is not adjusted because it was a planned contrast.) · Mean difference (net): -.59Active tDCS - sham tDCS.
  • Sham tDCS Preconditioning vs Sham tDCS Preconditioning of Active rTMS · Mixed Models Analysis · p = 0.0418 (This p value is not adjusted for multiple comparisons because it was a planned contrast.) · Mean difference (net): .36Sham tDCS - Sham tDCS and Active rTMS
  • Sham tDCS Preconditioning of Active rTMS vs Active tDCS Preconditioning of Active rTMS · Mixed Models Analysis · p = 0.40 (The p value is not adjusted as this was a planned contrast.) · Mean difference (net): -0.19Effect of tDCS preconditioning on active rTMS: active tDCS preconditioning of active rTMS - sham tDCS preconditioning of active rTMS.
  • Sham tDCS Preconditioning of Sham rTMS vs Active tDCS Preconditioning of Active rTMS · Mixed Models Analysis · p = .086 (The p value was not adjusted for this planned contrast.) · Mean difference (net): -0.48Active tDCS and Active rTMS - Sham tDCS and Sham rTMS.

Adverse events

Collected over Three lab visits over 6 weeks.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Cumulative Report of Adverse Events0/10 (0%)0/10 (0%)1/10 (10%)
Most frequent other events
Most frequent other events
EventCumulative Report of Adverse Events
HeadacheSkin and subcutaneous tissue disorders1/10

Baseline characteristics

Baseline characteristics are reported for the two arms to which subjects were assigned.

Age, Continuous
Age, Continuous(years)tDCS and 1 Hz rTMS Delivered Over TCtDCS and 1 Hz rTMS Delivered Over DLPFTotal
Mean35.8 ± 16.832 ± 15.1433.9 ± 14.16
Sex: Female, Male
Sex: Female, Male(Participants)tDCS and 1 Hz rTMS Delivered Over TCtDCS and 1 Hz rTMS Delivered Over DLPFTotal
Female448
Male112
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)tDCS and 1 Hz rTMS Delivered Over TCtDCS and 1 Hz rTMS Delivered Over DLPFTotal
Hispanic or Latino011
Not Hispanic or Latino549
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)tDCS and 1 Hz rTMS Delivered Over TCtDCS and 1 Hz rTMS Delivered Over DLPFTotal
American Indian or Alaska Native011
Asian011
Native Hawaiian or Other Pacific Islander000
Black or African American000
White527
More than one race000
Unknown or Not Reported011
Mean baseline P100 amplitude of the GMFA
Mean baseline P100 amplitude of the GMFA(µV)tDCS and 1 Hz rTMS Delivered Over TCtDCS and 1 Hz rTMS Delivered Over DLPFTotal
Mean1.29 ± 0.47—1.29 ± 0.47
07

Study locations

1 site
  • University of Arkansas for Medical Sciences
    Little Rock, Arkansas 72205, United States
08

References and documents

Study documents

  • Protocol and statistical analysis plan · Feb 26, 2018

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03309696
Lead sponsor
University of Arkansas
Responsible party
Sponsor
First posted
Oct 13, 2017
Start date
Nov 16, 2017
Primary completion
Oct 1, 2019
Completion
Oct 1, 2019
Results posted
Nov 6, 2020
Last update
Nov 17, 2020

Study contacts

Mark Mennemeier, PhD
principal investigator · University of Arkansas

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
Yes
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