Motor ActivityEarly Phase 1NCT03584438
iTBS Methods and Motor Cortex Excitability
A Early Phase 1 study testing Real iTBS in people with Motor Activity, run by Medical University of South Carolina at 1 site in United States.
Trial summary
In a recent publication by Gamboa et al. 20108 it was shown that extended theta-burst stimulation duration might have reverse effects on cortical excitability when compared to the original Huang et al. 2005 publication. While the post treatment effects of the original Huang et al. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Motor Activity
- What is being tested?
- Real iTBS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 26 May 2018to 7 Feb 2020
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy adults (18 - 65 years of age)
- Able to read and understand questionnaires and informed consent
Who cannot join
- Pregnancy, females of child bearing age must undergo a pregnancy test to confirm eligibility;
- History of seizure disorder or post-stroke seizure;
- Implanted medical devices or metal in head (except braces);
- Preexisting scalp lesion or wound or bone defect or hemicraniectomy;
- Left-hand dominance
Trial locations and contacts
1 site in 1 country.
United States1 site
Medical University of South Carolina
Charleston, South Carolina, 29425
About this study
Official title: The Effects of Theta-Burst Stimulation Duration on Human Motor Cortex Excitability
In a recent publication by Gamboa et al. 20108 it was shown that extended theta-burst stimulation duration might have reverse effects on cortical excitability when compared to the original Huang et al. 2005 publication. While the post treatment effects of the original Huang et al. 2005 protocol were successfully replicated, when continuous theta burst stimulation (cTBS) protocols were doubled to 1200 pulses over 80 seconds and the iTBS protocols were doubled to 1200 pulses over 390 seconds, there was increased facilitation after the prolonged cTBS and decreased excitability after prolonged iTBS. Currently there is an interest in optimizing repetitive transcranial magnetic stimulation (rTMS) protocols and in particular theta burst stimulation as both a therapeutic and an investigational tool. In Hanlon et al. 2015, a novel theta burst paradigm is described in which two trains of 1800 pulses of cTBS were administered, each train separated by a one-minute interval. In this study 11-cocaine dependent individuals underwent cTBS over the medial prefrontal cortex (MPFC) and showed attenuated craving as well as decreases in activity of the striatum and anterior insula. This study aims to replicate the findings of the Gamboa and Huang protocols as well as investigate how novel theta burst stimulation paradigms such as those described in Hanlon et al. 2015, which are currently being explored as therapeutic methods in addiction may change cortical excitability.
Read the detailed description
rTMS is a method of non-invasive neuromodulation. Although TMS (transcranial magnetic stimulation) has widely been used as a research method to better understand brain neurophysiology, rTMS protocols have been shown to be clinically beneficial to patients suffering from neurological disorders such as Parkinson's Disease and stroke as well as psychiatric diseases such as major depression. In October of 2008 the FDA approved 10 Hertz (Hz) dorsolateral prefrontal cortex (DLPFC) stimulation for patients with medication resistant depression. The typical duration of a single rTMS treatment for depression lasts for about 30 minutes, but must be repeated daily over several weeks. The decision to use DLPFC stimulation was due in part to imaging studies, which suggested depressed patients had decreased activity in the region. Thus, rTMS could be used to reverse those behavioral effects of depression by increasing activity in the DLPFC. Traditionally 5 Hertz (Hz) stimulation and upward has been shown to be excitatory while stimulation of 0.2-1 Hertz (Hz) has been shown to have inhibitory effects on the cortex. Although these parameters appear to be efficacious the development of new rTMS methods are still being explored.
Theta burst stimulation (TBS) is a method with the potential of providing excitatory or inhibitory effects on the cortex, which are as powerful as traditional rTMS methods yet more efficient in duration and intensity required. Evidence from previous studies looking at theta burst as a treatment for depression has highlighted the importance of the method's development. One study indicated that theta-burst stimulation over the dorsomedial prefrontal cortex (DMPFC) for a duration of just 6 minutes can produce comparable anti-depressant effects to traditional 10Hz stimulation over 30 minutes. Theta burst stimulation effects were first empirically tested on the human motor cortex by Huang et al. 2005. The effects of stimulation (80% of active motor threshold) over the motor cortex were measured pre and post treatment with electromyography (EMG) recordings of motor evoked potentials (MEPs) on a small contralateral hand muscle in response to single pulses of TMS. Two protocols showed changes in excitability of the corticospinal tract, including cTBS defined as three burst stimuli at 50 Hz with 20ms between stimuli repeated every 200ms at 5Hz and iTBS defined as a 2s train of TBS repeated every 10 seconds. Although both protocols deliver a total of 600 pulses, the cTBS protocols lasts for 40 seconds while the iTBS protocol lasts for 190 seconds. Huang et al. 2005 determined that cTBS over motor cortex decreased excitability while iTBS increased excitability which were present an hour following treatment.
The excitability of the motor cortex may be modulated differently depending on the type of theta burst stimulation protocol utilized. iTBS was originally described by Huang et al. 2005 resulting in an excitatory effects (LTP like) on the cortex. Gamboa et al. 2010 later confirmed this finding but showed that there was a decrease in excitability (LTD-like) when the protocol is doubled. Both of these protocols are to be replicated and in addition 2 new protocols. In order to investigate how cortical excitability changes as a function of protocol, MEPs will be recorded using EMG on the hand muscle contralateral to the stimulated cortex. Baseline MEPs will be obtained pretreatment, followed by one of the four theta burst protocols, or a sham treatment. Theta burst protocols are to be administered to each participant in randomized order. After theta burst is administered 20 MEPs will be collected at 0, 10, 20, 30, 40, 50 and 60 minutes.
Specific Aim 1: To determine the long-term potentiation (LTP) like and long-term depression (LTD) like effects of four different theta burst stimulation protocols on motor cortex excitability.
- Conditions
- Motor Activity
- Being tested
- Real iTBS, Sham iTBS
- Keywords
- TMS, Motor Cortex, Excitability, LTP, LTD
- Medical subject headings
- Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Real iTBSDevice
This will be delivered with the Magventure Magpro system; pulses are delivered with the active coil (double blinded using the Universal Serial Bus key)
Sham iTBSDevice
This will be delivered with the Magventure Magpro system; pulses are delivered with the sham coil (double blinded using the Universal Serial Bus key). The MagVenture MagPro system has an integrated active sham that passes current through two surface electrodes placed on the skin beneath the B60 coil.
| Study group | Role | What they receive |
|---|---|---|
| Hanlon Real iTBS Protocol 1 | Experimental | One session of real intermittent Theta Burst Stimulation (iTBS) will be delivered to the left motor cortex. 600 pulses of iTBS over the motor cortex (C3), 3600 pulses are delivered over 19 minutes. Receives: Device: Real iTBS |
| Hanlon Real iTBS Protocol 2 | Experimental | One session of real intermittent Theta Burst Stimulation (iTBS) will be delivered to the left motor cortex. 600 pulses of iTBS over the motor cortex (C3), 1800 pulses are delivered over 9 minutes and 30 seconds. Receives: Device: Real iTBS |
| Huang Real iTBS Protocol | Experimental | One session of real intermittent Theta Burst Stimulation (iTBS) will be delivered to the left motor cortex. (2 sec trains of tbs every 10 sec) was applied over the left motor cortex (C3) for 190 seconds (a total of 600 TMS pulses). Receives: Device: Real iTBS |
| Gamboa Real iTBS Protocol | Experimental | One session of real intermittent Theta Burst Stimulation (iTBS) will be delivered to the left motor cortex. (2 sec trains of tbs every 10 sec) was applied over the left motor cortex (C3) for 380 seconds (a total of 1200 TMS pulses). Receives: Device: Real iTBS |
| Sham iTBS protocol | Sham comparator | One session of sham intermittent Theta Burst Stimulation (iTBS) will be delivered to the left motor cortex. The MagVenture MagPro system has an integrated active sham that passes current through two surface electrodes placed on the skin over the left motor cortex (C3) and beneath the coil. Receives: Device: Sham iTBS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effects of theta burst stimulation protocols of LTP-like and LTD-like stimulation on change in motor cortex excitability
The excitability of the motor cortex may be modulated differently depending on the type of TBS protocol utilized. iTBS was originally described by Huang et al. 20057 resulting in an excitatory effects (LTP like) on the cortex. Gamboa et al. 20108 later confirmed this finding but showed that there was a decrease in excitability (LTD-like) when the protocol is doubled. Both of these protocols are to be replicated and in addition 2 new protocols. In order to investigate how cortical excitability changes as a function of protocol, MEPs (motor evoked potentials) will be recorded using EMG (electromyography) on the hand muscle contralateral to the stimulated cortex. Baseline MEPs will be obtained pretreatment, followed by one of the four theta burst protocols, or a sham treatment. Theta burst protocols are to be administered to each participant in randomized order. After theta burst is administered 20 MEPs will be collected at 0, 10, 20, 30, 40, 50 and 60 minutes.
Measured: Through study completion, an average of two weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2018
- Study start26 May 2018
- Primary completion7 Feb 2020
- Study completion7 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Motor ActivityStudies 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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 30 healthy controls will undergo four Active TMS treatment sessions (separated by at least 24 hrs), along with a Sham TMS treatment session. The theta-burst treatments will be counterbalanced across participants.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of South Carolina
- Sponsor type
- University, hospital or other
- Collaborators
- MUSC Center for Biomedical Research Excellence in Stroke Recovery
- Responsible party
- Sponsor
- Investigators
- Lisa McTeague, PhD, Principal investigator, Medical University of South Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03584438
- Sponsor's protocol ID
- 68775
- Status last verified
- Mar 2020
- First submitted
- 15 Jun 2018
- Last updated
- 12 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Theta-Burst Stimulation Duration on Human Motor Cortex Excitability
- ClinicalTrials.gov ID
- NCT03584438
- Acronym / sponsor ID
- 68775
- Conditions
- Motor Activity
- Keywords
- TMS, Motor Cortex, Excitability, LTP, LTD
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Medical University of South CarolinaUniversity, hospital or other
- Collaborators
- MUSC Center for Biomedical Research Excellence in Stroke Recovery
- Study start
- 26 May 2018 (actual)
- Primary completion
- 7 Feb 2020 (actual)
- Study completion
- 7 Feb 2020 (actual)
- First posted
- 12 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In a recent publication by Gamboa et al. 20108 it was shown that extended theta-burst stimulation duration might have reverse effects on cortical excitability when compared to the original Huang et al. 2005 publication. While the post treatment effects of the original Huang et al. 2005 protocol were successfully replicated, when continuous theta burst stimulation (cTBS) protocols were doubled to 1200 pulses over 80 seconds and the iTBS protocols were doubled to 1200 pulses over 390 seconds, there was increased facilitation after the prolonged cTBS and decreased excitability after prolonged iTBS. Currently there is an interest in optimizing repetitive transcranial magnetic stimulation (rTMS) protocols and in particular theta burst stimulation as both a therapeutic and an investigational tool. In Hanlon et al. 2015, a novel theta burst paradigm is described in which two trains of 1800 pulses of cTBS were administered, each train separated by a one-minute interval. In this study 11-cocaine dependent individuals underwent cTBS over the medial prefrontal cortex (MPFC) and showed attenuated craving as well as decreases in activity of the striatum and anterior insula. This study aims to replicate the findings of the Gamboa and Huang protocols as well as investigate how novel theta burst stimulation paradigms such as those described in Hanlon et al. 2015, which are currently being explored as therapeutic methods in addiction may change cortical excitability.
Detailed description
rTMS is a method of non-invasive neuromodulation. Although TMS (transcranial magnetic stimulation) has widely been used as a research method to better understand brain neurophysiology, rTMS protocols have been shown to be clinically beneficial to patients suffering from neurological disorders such as Parkinson's Disease and stroke as well as psychiatric diseases such as major depression. In October of 2008 the FDA approved 10 Hertz (Hz) dorsolateral prefrontal cortex (DLPFC) stimulation for patients with medication resistant depression. The typical duration of a single rTMS treatment for depression lasts for about 30 minutes, but must be repeated daily over several weeks. The decision to use DLPFC stimulation was due in part to imaging studies, which suggested depressed patients had decreased activity in the region. Thus, rTMS could be used to reverse those behavioral effects of depression by increasing activity in the DLPFC. Traditionally 5 Hertz (Hz) stimulation and upward has been shown to be excitatory while stimulation of 0.2-1 Hertz (Hz) has been shown to have inhibitory effects on the cortex. Although these parameters appear to be efficacious the development of new rTMS methods are still being explored.
Theta burst stimulation (TBS) is a method with the potential of providing excitatory or inhibitory effects on the cortex, which are as powerful as traditional rTMS methods yet more efficient in duration and intensity required. Evidence from previous studies looking at theta burst as a treatment for depression has highlighted the importance of the method's development. One study indicated that theta-burst stimulation over the dorsomedial prefrontal cortex (DMPFC) for a duration of just 6 minutes can produce comparable anti-depressant effects to traditional 10Hz stimulation over 30 minutes. Theta burst stimulation effects were first empirically tested on the human motor cortex by Huang et al. 2005. The effects of stimulation (80% of active motor threshold) over the motor cortex were measured pre and post treatment with electromyography (EMG) recordings of motor evoked potentials (MEPs) on a small contralateral hand muscle in response to single pulses of TMS. Two protocols showed changes in excitability of the corticospinal tract, including cTBS defined as three burst stimuli at 50 Hz with 20ms between stimuli repeated every 200ms at 5Hz and iTBS defined as a 2s train of TBS repeated every 10 seconds. Although both protocols deliver a total of 600 pulses, the cTBS protocols lasts for 40 seconds while the iTBS protocol lasts for 190 seconds. Huang et al. 2005 determined that cTBS over motor cortex decreased excitability while iTBS increased excitability which were present an hour following treatment.
The excitability of the motor cortex may be modulated differently depending on the type of theta burst stimulation protocol utilized. iTBS was originally described by Huang et al. 2005 resulting in an excitatory effects (LTP like) on the cortex. Gamboa et al. 2010 later confirmed this finding but showed that there was a decrease in excitability (LTD-like) when the protocol is doubled. Both of these protocols are to be replicated and in addition 2 new protocols. In order to investigate how cortical excitability changes as a function of protocol, MEPs will be recorded using EMG on the hand muscle contralateral to the stimulated cortex. Baseline MEPs will be obtained pretreatment, followed by one of the four theta burst protocols, or a sham treatment. Theta burst protocols are to be administered to each participant in randomized order. After theta burst is administered 20 MEPs will be collected at 0, 10, 20, 30, 40, 50 and 60 minutes.
Specific Aim 1: To determine the long-term potentiation (LTP) like and long-term depression (LTD) like effects of four different theta burst stimulation protocols on motor cortex excitability.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 5
- Model description
- 30 healthy controls will undergo four Active TMS treatment sessions (separated by at least 24 hrs), along with a Sham TMS treatment session. The theta-burst treatments will be counterbalanced across participants.
| Arm | Type | Receives |
|---|---|---|
| Hanlon Real iTBS Protocol 1 | Experimental | Device: Real iTBSOne session of real intermittent Theta Burst Stimulation (iTBS) will be delivered to the left motor cortex. 600 pulses of iTBS over the motor cortex (C3), 3600 pulses are delivered over 19 minutes. |
| Hanlon Real iTBS Protocol 2 | Experimental | Device: Real iTBSOne session of real intermittent Theta Burst Stimulation (iTBS) will be delivered to the left motor cortex. 600 pulses of iTBS over the motor cortex (C3), 1800 pulses are delivered over 9 minutes and 30 seconds. |
| Huang Real iTBS Protocol | Experimental | Device: Real iTBSOne session of real intermittent Theta Burst Stimulation (iTBS) will be delivered to the left motor cortex. (2 sec trains of tbs every 10 sec) was applied over the left motor cortex (C3) for 190 seconds (a total of 600 TMS pulses). |
| Gamboa Real iTBS Protocol | Experimental | Device: Real iTBSOne session of real intermittent Theta Burst Stimulation (iTBS) will be delivered to the left motor cortex. (2 sec trains of tbs every 10 sec) was applied over the left motor cortex (C3) for 380 seconds (a total of 1200 TMS pulses). |
| Sham iTBS protocol | Sham comparator | Device: Sham iTBSOne session of sham intermittent Theta Burst Stimulation (iTBS) will be delivered to the left motor cortex. The MagVenture MagPro system has an integrated active sham that passes current through two surface electrodes placed on the skin over the left motor cortex (C3) and beneath the coil. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Healthy adults (18 - 65 years of age)
- Able to read and understand questionnaires and informed consent
Key exclusion criteria (5 listed)
- Pregnancy, females of child bearing age must undergo a pregnancy test to confirm eligibility;
- History of seizure disorder or post-stroke seizure;
- Implanted medical devices or metal in head (except braces);
- Preexisting scalp lesion or wound or bone defect or hemicraniectomy;
- Left-hand dominance
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 |
|---|---|---|
| Real iTBSThis will be delivered with the Magventure Magpro system; pulses are delivered with the active coil (double blinded using the Universal Serial Bus key) | Device | Gamboa Real iTBS Protocol, Hanlon Real iTBS Protocol 1, Hanlon Real iTBS Protocol 2, Huang Real iTBS Protocol |
| Sham iTBSThis will be delivered with the Magventure Magpro system; pulses are delivered with the sham coil (double blinded using the Universal Serial Bus key). The MagVenture MagPro system has an integrated active sham that passes current through two surface electrodes placed on the skin beneath the B60 coil. | Device | Sham iTBS protocol |
Primary outcome
Effects of theta burst stimulation protocols of LTP-like and LTD-like stimulation on change in motor cortex excitability
Time frame: Through study completion, an average of two weeks.
The excitability of the motor cortex may be modulated differently depending on the type of TBS protocol utilized. iTBS was originally described by Huang et al. 20057 resulting in an excitatory effects (LTP like) on the cortex. Gamboa et al. 20108 later confirmed this finding but showed that there was a decrease in excitability (LTD-like) when the protocol is doubled. Both of these protocols are to be replicated and in addition 2 new protocols. In order to investigate how cortical excitability changes as a function of protocol, MEPs (motor evoked potentials) will be recorded using EMG (electromyography) on the hand muscle contralateral to the stimulated cortex. Baseline MEPs will be obtained pretreatment, followed by one of the four theta burst protocols, or a sham treatment. Theta burst protocols are to be administered to each participant in randomized order. After theta burst is administered 20 MEPs will be collected at 0, 10, 20, 30, 40, 50 and 60 minutes.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2020.
- Individual participant dataSharing planned: No
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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.
Lisa McTeague, PhD principal investigator
Medical University of South Carolina
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Real iTBS in people with Motor Activity, run by Medical University of South Carolina 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 2 inclusion and 5 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: finished, as of the sponsor's last update on 12 Mar 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Effects of theta burst stimulation protocols of LTP-like and LTD-like stimulation on change in motor cortex excitability (time frame: Through study completion, an average of two 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 12 Mar 2020.