DysphagiaNCT03831789
The Effects of Bilateral Cerebellar rTMS on Cortical Function
A study testing Cerebellar targeted rTMS in people with Dysphagia and Swallowing Disorder, run by University of Manchester at 1 site in United Kingdom.
Trial summary
Swallowing function is controlled by two swallowing centres (one on each half of the brain). There is a dominant and non-dominant swallowing centre. Damage to any part of the brain can lead to swallowing problems, for example in strokes. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Dysphagia, Swallowing Disorder
- What is being tested?
- Cerebellar targeted rTMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 8 Apr 2019to 30 Apr 2020
- Phase
- Interventional
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Adults above 18 years of age
Who cannot join
- Epilepsy
- Cardiac pacemaker
- Previous brain surgery
- Previous swallowing problems
- The use of medication which acts on the central nervous system
- Any implanted metal in the head
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Upper G.I laboratory, Salford Royal Hospital
Manchester, Greater Manchester, M6 8HD
About this study
Official title: The Neurophysiological Effects of Bilateral Cerebellar rTMS on Cortical Activity and Swallowing Function
Swallowing function is controlled by two swallowing centres (one on each half of the brain). There is a dominant and non-dominant swallowing centre. Damage to any part of the brain can lead to swallowing problems, for example in strokes. Recovery of the ability to swallow is associated with increased activity (compensation) over the undamaged centre. The cerebellum is an area of the brain involved in the control and modulation of muscle movements. It is found at the back of the skull.
Over the past few years studies have tried to improve swallowing function using techniques to stimulate regions of the brain and encourage compensation. Repetitive transcranial magnetic stimulation (rTMS) is a technique which can temporarily increase or suppress activity over regions of the brain.
This study will use cerebellar rTMS to attempt to increase activity over the cortical swallowing centres. It will also temporarily suppress activity over the dominant swallowing centre (a virtual lesion) before using cerebellar targeted rTMS to attempt to reverse this suppressive electrical and behavioural effect. The investigators aim to compare the effectiveness of rTMS over the two halves of the cerebellum to rTMS over one half of the cerebellum in increasing activity over the swallowing centres and reversing the suppressive effects of low frequency rTMS 'virtual lesion' over the dominant swallowing centre.
Read the detailed description
Summary
To determine if 10 Hertz bilateral cerebellar rTMS is more effective than 10 Hertz unilateral cerebellar rTMS or sham in:
- Increasing PMEP amplitude over the pharyngeal cortical area
- Reversing focal cortical suppression to the pharyngeal motor cortex induced by a 'virtual lesion'.
This experiment will be performed over six visits to the laboratory.
Experiment Previous studies in our laboratory have shown that focal suppression of the strongest pharyngeal motor representation (1 Hz rTMS for 10 minutes at an intensity of 120% of resting motor threshold) transiently suppresses cortical swallowing activity as measured by PMEP amplitude and function as measured by a swallowing reaction time task, for up to an hour after cessation of rTMS (14, 15). This temporary suppressive effect has been called a cortical 'virtual lesion'. This model has been utilised in several studies (2, 14, 15) as a way of trialling the effects of neurostimulatory interventions in a safe, controlled environment in healthy subjects, before proceeding to patient trials. Studies have also shown that interventions which are capable of reversing the effects of focal cortical suppression more quickly than would ordinarily be the case if the suppressive effects were left to dissipate naturally, are effective in improving post stroke dysphagia (16).
The optimal stimulation sites for the pharyngeal cortical areas and cerebellum will have their resting motor thresholds identified and marked using single pulse TMS with a figure of eight coil (wing diameter of 90mm). Anatomical landmarks will be used to help guide neuronavigation. The vertex of the head will be identified with a tape measure as will the inion (the most prominent part at the back of the skull) (1). Studies have demonstrated that the pharyngeal cortical area is found anterior and lateral to the vertex while both halves of the cerebellum lie inferior and lateral to the inion (1, 15).
Visits 1- 2 (Aim 1 Measurement of Pharyngeal Cortical MEP Amplitude) Cortical and cerebellar PMEPs will be measured by administering single pulse TMS at 10% of stimulator output above resting motor threshold. Ten stimuli (trials) will be given over the pharyngeal motor cortex with greater neuronal activity - lower resting membrane threshold. This stimulus intensity has been shown to give the best reproducibility results for viscerosomatic TMS studies (15). Cerebellar MEPs will be measured by administering 5 stimuli (trials) of single pulse TMS over the cerebellum.
Participants will be randomised to receive one of two cerebellar rTMS interventions (on separate visits):
- Real 10 Hz cerebellar rTMS (250 pulses) to the right cerebellar hemisphere (unilateral)
- Real 10 Hz cerebellar rTMS (250 pulses) to the right and left cerebellar hemispheres (bilateral) The effects of the interventions on PMEPs over cortical pharyngeal areas bilaterally will be measured immediately and every fifteen minutes for an hour post intervention. All data will be compared to baseline MEP amplitude. Visits 3-4 (Aim 2 Measurement of Pharyngeal Cortical MEP Amplitude after Virtual Lesion) A 'virtual lesion' (1 Hz rTMS for 10 minutes at an intensity of 120% of resting motor threshold) will be administered by holding a figure of eight coil flat over the cortical pharyngeal representation with the highest neurological activity - this is the representation with the lowest resting membrane potential (15). After which, over two visits to the laboratory, unilateral and bilateral cerebellar rTMS will administered to the cerebellar sites identified earlier. During these two visits participants will have their baseline pharyngeal MEPs measured in a similar manner to visits 1-2. After focal cortical suppression subjects will be randomised to receive one of two cerebellar rTMS interventions (on separate visits):
- Real 10 Hz cerebellar rTMS (250 pulses) to the right cerebellar hemisphere (unilateral)
- Real 10 Hz cerebellar rTMS (250 pulses) to the right and left cerebellar hemispheres (bilateral) The effects of the interventions on PMEPs over cortical pharyngeal areas bilaterally will then be measured immediately and every fifteen minutes for an hour post intervention before being compared to baseline. Visits 5-6 (Aim 2 Measurement of Swallowing Accuracy Using Reaction Time Task) During these two visits, subjects will have baseline measurements of normal, fast and challenge swallows (*see below for measurement procedure). After focal cortical suppression subjects will be randomised to receive one of two cerebellar rTMS interventions (on separate visits):
- Real 10 Hz cerebellar rTMS (250 pulses) to the right cerebellar hemisphere (unilateral)
- Real 10 Hz cerebellar rTMS (250 pulses) to the right and left cerebellar hemispheres (bilateral)
The effects of the interventions on swallowing function will then be measured by repeating normal, fast and challenge swallow reaction times, immediately and at regular intervals for an hour post intervention.
- Conditions
- Dysphagia, Swallowing Disorder
- Being tested
- Cerebellar targeted rTMS
- Medical subject headings
- Deglutition Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cerebellar targeted rTMSDevice
10 Hz cerebellar rTMS (250 pulses)
| Study group | Role | What they receive |
|---|---|---|
| Unilateral cerebellar rTMS | Active comparator | Not described Receives: Device: Cerebellar targeted rTMS |
| Bilateral cerebellar rTMS | Experimental | Not described Receives: Device: Cerebellar targeted rTMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
PMEP
Pharyngeal motor evoked potential amplitude (PMEP) amplitude
Measured: Every 15 minutes for an hour after the intervention.
Swallowing behaviour
Swallowing accuracy (number of correct swallows on target out of 10 using a swallowing reaction time task)
Measured: Every 15 minutes for an hour after the intervention.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2019
- Study start8 Apr 2019
- Primary completion30 Mar 2020
- Study completion30 Apr 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DysphagiaStudies 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
- Crossover
- Model description
- All participants over the course of three visits will either have: unilateral cerebellar rTMS or bilateral cerebellar rTMS. However, the order in which they will receive these interventions will be randomly allocated.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Manchester
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof Shaheen Hamdy PhD FRCP, University of Manchester
- Investigators
- Shaheen Hamdy, Principal investigator, University of Manchester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03831789
- Sponsor's protocol ID
- IRAS 256171
- Status last verified
- Jun 2022
- First submitted
- 4 Feb 2019
- Last updated
- 9 Jun 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: IPD containing personal identifiable information will not be published. However, anonymised PMEP and swallowing timing data will be published.
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Neurophysiological Effects of Bilateral Cerebellar rTMS on Cortical Activity and Swallowing Function
- ClinicalTrials.gov ID
- NCT03831789
- Acronym / sponsor ID
- IRAS 256171
- Conditions
- Dysphagia, Swallowing Disorder
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University of ManchesterUniversity, hospital or other
- Study start
- 8 Apr 2019 (actual)
- Primary completion
- 30 Mar 2020 (actual)
- Study completion
- 30 Apr 2020 (actual)
- First posted
- 6 Feb 2019 (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.
Swallowing function is controlled by two swallowing centres (one on each half of the brain). There is a dominant and non-dominant swallowing centre. Damage to any part of the brain can lead to swallowing problems, for example in strokes. Recovery of the ability to swallow is associated with increased activity (compensation) over the undamaged centre. The cerebellum is an area of the brain involved in the control and modulation of muscle movements. It is found at the back of the skull.
Over the past few years studies have tried to improve swallowing function using techniques to stimulate regions of the brain and encourage compensation. Repetitive transcranial magnetic stimulation (rTMS) is a technique which can temporarily increase or suppress activity over regions of the brain.
This study will use cerebellar rTMS to attempt to increase activity over the cortical swallowing centres. It will also temporarily suppress activity over the dominant swallowing centre (a virtual lesion) before using cerebellar targeted rTMS to attempt to reverse this suppressive electrical and behavioural effect. The investigators aim to compare the effectiveness of rTMS over the two halves of the cerebellum to rTMS over one half of the cerebellum in increasing activity over the swallowing centres and reversing the suppressive effects of low frequency rTMS 'virtual lesion' over the dominant swallowing centre.
Detailed description
Summary
To determine if 10 Hertz bilateral cerebellar rTMS is more effective than 10 Hertz unilateral cerebellar rTMS or sham in:
- Increasing PMEP amplitude over the pharyngeal cortical area
- Reversing focal cortical suppression to the pharyngeal motor cortex induced by a 'virtual lesion'.
This experiment will be performed over six visits to the laboratory.
Experiment Previous studies in our laboratory have shown that focal suppression of the strongest pharyngeal motor representation (1 Hz rTMS for 10 minutes at an intensity of 120% of resting motor threshold) transiently suppresses cortical swallowing activity as measured by PMEP amplitude and function as measured by a swallowing reaction time task, for up to an hour after cessation of rTMS (14, 15). This temporary suppressive effect has been called a cortical 'virtual lesion'. This model has been utilised in several studies (2, 14, 15) as a way of trialling the effects of neurostimulatory interventions in a safe, controlled environment in healthy subjects, before proceeding to patient trials. Studies have also shown that interventions which are capable of reversing the effects of focal cortical suppression more quickly than would ordinarily be the case if the suppressive effects were left to dissipate naturally, are effective in improving post stroke dysphagia (16).
The optimal stimulation sites for the pharyngeal cortical areas and cerebellum will have their resting motor thresholds identified and marked using single pulse TMS with a figure of eight coil (wing diameter of 90mm). Anatomical landmarks will be used to help guide neuronavigation. The vertex of the head will be identified with a tape measure as will the inion (the most prominent part at the back of the skull) (1). Studies have demonstrated that the pharyngeal cortical area is found anterior and lateral to the vertex while both halves of the cerebellum lie inferior and lateral to the inion (1, 15).
Visits 1- 2 (Aim 1 Measurement of Pharyngeal Cortical MEP Amplitude) Cortical and cerebellar PMEPs will be measured by administering single pulse TMS at 10% of stimulator output above resting motor threshold. Ten stimuli (trials) will be given over the pharyngeal motor cortex with greater neuronal activity - lower resting membrane threshold. This stimulus intensity has been shown to give the best reproducibility results for viscerosomatic TMS studies (15). Cerebellar MEPs will be measured by administering 5 stimuli (trials) of single pulse TMS over the cerebellum.
Participants will be randomised to receive one of two cerebellar rTMS interventions (on separate visits):
- Real 10 Hz cerebellar rTMS (250 pulses) to the right cerebellar hemisphere (unilateral)
- Real 10 Hz cerebellar rTMS (250 pulses) to the right and left cerebellar hemispheres (bilateral) The effects of the interventions on PMEPs over cortical pharyngeal areas bilaterally will be measured immediately and every fifteen minutes for an hour post intervention. All data will be compared to baseline MEP amplitude. Visits 3-4 (Aim 2 Measurement of Pharyngeal Cortical MEP Amplitude after Virtual Lesion) A 'virtual lesion' (1 Hz rTMS for 10 minutes at an intensity of 120% of resting motor threshold) will be administered by holding a figure of eight coil flat over the cortical pharyngeal representation with the highest neurological activity - this is the representation with the lowest resting membrane potential (15). After which, over two visits to the laboratory, unilateral and bilateral cerebellar rTMS will administered to the cerebellar sites identified earlier. During these two visits participants will have their baseline pharyngeal MEPs measured in a similar manner to visits 1-2. After focal cortical suppression subjects will be randomised to receive one of two cerebellar rTMS interventions (on separate visits):
- Real 10 Hz cerebellar rTMS (250 pulses) to the right cerebellar hemisphere (unilateral)
- Real 10 Hz cerebellar rTMS (250 pulses) to the right and left cerebellar hemispheres (bilateral) The effects of the interventions on PMEPs over cortical pharyngeal areas bilaterally will then be measured immediately and every fifteen minutes for an hour post intervention before being compared to baseline. Visits 5-6 (Aim 2 Measurement of Swallowing Accuracy Using Reaction Time Task) During these two visits, subjects will have baseline measurements of normal, fast and challenge swallows (*see below for measurement procedure). After focal cortical suppression subjects will be randomised to receive one of two cerebellar rTMS interventions (on separate visits):
- Real 10 Hz cerebellar rTMS (250 pulses) to the right cerebellar hemisphere (unilateral)
- Real 10 Hz cerebellar rTMS (250 pulses) to the right and left cerebellar hemispheres (bilateral)
The effects of the interventions on swallowing function will then be measured by repeating normal, fast and challenge swallow reaction times, immediately and at regular intervals for an hour post intervention.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- All participants over the course of three visits will either have: unilateral cerebellar rTMS or bilateral cerebellar rTMS. However, the order in which they will receive these interventions will be randomly allocated.
| Arm | Type | Receives |
|---|---|---|
| Unilateral cerebellar rTMS | Active comparator | Device: Cerebellar targeted rTMS |
| Bilateral cerebellar rTMS | Experimental | Device: Cerebellar targeted rTMS |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Adults above 18 years of age
Key exclusion criteria (6 listed)
- Epilepsy
- Cardiac pacemaker
- Previous brain surgery
- Previous swallowing problems
- The use of medication which acts on the central nervous system
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 |
|---|---|---|
| Cerebellar targeted rTMS10 Hz cerebellar rTMS (250 pulses) | Device | Bilateral cerebellar rTMS, Unilateral cerebellar rTMS |
Primary outcome
PMEP
Time frame: Every 15 minutes for an hour after the intervention.
Pharyngeal motor evoked potential amplitude (PMEP) amplitude
Swallowing behaviour
Time frame: Every 15 minutes for an hour after the intervention.
Swallowing accuracy (number of correct swallows on target out of 10 using a swallowing reaction time task)
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 9 Jun 2022.
- Individual participant dataSharing planned: No. IPD containing personal identifiable information will not be published. However, anonymised PMEP and swallowing timing data will be published.
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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.
Shaheen Hamdy principal investigator
University of Manchester
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cerebellar targeted rTMS in people with Dysphagia and Swallowing Disorder, run by University of Manchester at 1 site in United Kingdom.
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 1 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: finished, as of the sponsor's last update on 9 Jun 2022. 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 Kingdom. 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?
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?
PMEP (time frame: Every 15 minutes for an hour after the intervention.). The study lists 2 primary outcomes in all. 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 9 Jun 2022.