Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03831789 |
| Other study ID # |
IRAS 256171 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
April 8, 2019 |
| Est. completion date |
April 30, 2020 |
Study information
| Verified date |
June 2022 |
| Source |
University of Manchester |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical 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. 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.
Description:
Summary
To determine if 10 Hertz bilateral cerebellar rTMS is more effective than 10 Hertz unilateral
cerebellar rTMS or sham in:
1. Increasing PMEP amplitude over the pharyngeal cortical area
2. 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):
1. Real 10 Hz cerebellar rTMS (250 pulses) to the right cerebellar hemisphere (unilateral)
2. 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):
3. Real 10 Hz cerebellar rTMS (250 pulses) to the right cerebellar hemisphere (unilateral)
4. 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):
5. Real 10 Hz cerebellar rTMS (250 pulses) to the right cerebellar hemisphere (unilateral)
6. 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.
