TinnitusNCT03309696
Regulating Homeostatic Plasticity and the Physiological Response to rTMS
A study testing active tDCS and active rTMS in people with Tinnitus, run by University of Arkansas at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Tinnitus
- What is being tested?
- active tDCS and active rTMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Nov 2017to 1 Oct 2019
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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,
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
About this study
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.
- Conditions
- Tinnitus
- Being tested
- sham tDCS and sham rTMS, sham tDCS and active rTMS, active tDCS and active rTMS
- Medical subject headings
- Tinnitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sham tDCS and sham rTMSDevice
Also called transcranial direct current stimulation (tDCS), repetative transcranial magnetic stimulation (rTMS)
Both combinations of tDCS and rTMS in this intervention are sham.
sham tDCS and active rTMSDevice
Also called transcranial direct current stimulation (tDCS), repetative transcranial magnetic stimulation (rTMS)
tDCS in this intervention is sham and rTMS is active
active tDCS and active rTMSDevice
Also called transcranial direct current stimulation (tDCS), repetative transcranial magnetic stimulation (rTMS)
Both combinations of tDCS and rTMS in this intervention are active
| Study group | Role | What they receive |
|---|---|---|
| tDCS and 1 Hz rTMS delivered over TC | Experimental | 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. . Receives: Device: sham tDCS and sham rTMS; Device: sham tDCS and active rTMS; Device: active tDCS and active rTMS |
| tDCS and 10Hz rTMS delivered over TC | Experimental | 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. Receives: Device: sham tDCS and sham rTMS; Device: sham tDCS and active rTMS; Device: active tDCS and active rTMS |
| tDCS over DLFC and 1 Hz rTMS over TC | Experimental | 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. Receives: Device: sham tDCS and sham rTMS; Device: sham tDCS and active rTMS; Device: active tDCS and active rTMS |
| tDCS over DLFC and 10 Hz rTMS over TC | Experimental | 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. Receives: Device: sham tDCS and sham rTMS; Device: sham tDCS and active rTMS; Device: active tDCS and active rTMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Up to 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2017
- Study start16 Nov 2017
- Primary completion1 Oct 2019
- Study completion1 Oct 2019
Why it stopped: Funding issues
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for TinnitusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arkansas
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mark Mennemeier, PhD, Principal investigator, University of Arkansas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03309696
- Sponsor's protocol ID
- 206326
- Status last verified
- Nov 2020
- First submitted
- 9 Oct 2017
- Last updated
- 17 Nov 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Regulating Homeostatic Plasticity and the Physiological Response to rTMS
- ClinicalTrials.gov ID
- NCT03309696
- Acronym / sponsor ID
- 206326
- Conditions
- Tinnitus
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding issues
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of ArkansasUniversity, hospital or other
- Study start
- 16 Nov 2017 (actual)
- Primary completion
- 1 Oct 2019 (actual)
- Study completion
- 1 Oct 2019 (actual)
- First posted
- 13 Oct 2017 (actual)
- Results
- Posted 6 Nov 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 4
- 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.
| Arm | Type | Receives |
|---|---|---|
| tDCS and 1 Hz rTMS delivered over TC | Experimental | Device: sham tDCS and sham rTMS, Device: sham tDCS and active rTMS, Device: active tDCS and active rTMSParticipants 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. . |
| tDCS and 10Hz rTMS delivered over TC | Experimental | Device: sham tDCS and sham rTMS, Device: sham tDCS and active rTMS, Device: active tDCS and active rTMSParticipants 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. |
| tDCS over DLFC and 1 Hz rTMS over TC | Experimental | Device: sham tDCS and sham rTMS, Device: sham tDCS and active rTMS, Device: active tDCS and active rTMSParticipants 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. |
| tDCS over DLFC and 10 Hz rTMS over TC | Experimental | Device: sham tDCS and sham rTMS, Device: sham tDCS and active rTMS, Device: active tDCS and active rTMSParticipants 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. |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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).
Key exclusion criteria (6 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sham tDCS and sham rTMSAlso: transcranial direct current stimulation (tDCS), repetative transcranial magnetic stimulation (rTMS)Both combinations of tDCS and rTMS in this intervention are sham. | Device | tDCS and 1 Hz rTMS delivered over TC, tDCS and 10Hz rTMS delivered over TC, tDCS over DLFC and 1 Hz rTMS over TC, tDCS over DLFC and 10 Hz rTMS over TC |
| sham tDCS and active rTMSAlso: transcranial direct current stimulation (tDCS), repetative transcranial magnetic stimulation (rTMS)tDCS in this intervention is sham and rTMS is active | Device | tDCS and 1 Hz rTMS delivered over TC, tDCS and 10Hz rTMS delivered over TC, tDCS over DLFC and 1 Hz rTMS over TC, tDCS over DLFC and 10 Hz rTMS over TC |
| active tDCS and active rTMSAlso: transcranial direct current stimulation (tDCS), repetative transcranial magnetic stimulation (rTMS)Both combinations of tDCS and rTMS in this intervention are active | Device | tDCS and 1 Hz rTMS delivered over TC, tDCS and 10Hz rTMS delivered over TC, tDCS over DLFC and 1 Hz rTMS over TC, tDCS over DLFC and 10 Hz rTMS over TC |
Primary outcome
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).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Mennemeier, PhD principal investigator
University of Arkansas
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing active tDCS and active rTMS in people with Tinnitus, run by University of Arkansas at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Nov 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Log Transformed P100 Amplitude of TEPs From the Global Mean Field Analysis. (time frame: Up to 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Nov 2020.