Cerebellar Metaplasticity in the Swallowing Motor System

Dysphagia is common and leads to significant morbidity and mortality within healthcare settings. Current approaches to dysphagia management involve altering the consistency of food and fluids. However, these approaches are not supported by a robust evidence base. Repetitive transcranial magnetic stimulation (rTMS) offers a non-invasive way to manipulate neuroelectric activity within the brain. Within the swallowing motor system, rTMS at a frequency of 5Hertz (Hz) and above is excitatory while 1Hz is suppressive.

Cortical rTMS targeting pharyngeal motor areas can alter brain activity and swallowing behaviour in healthy participants and has been shown to improve post-stroke dysphagia (PSD). Despite this, it has a small seizure risk. Cerebellar rTMS is a newer and safer technique which is more easily targeted and is effective at altering swallowing related brain activity and behaviour. Recent studies have also shown it can improve PSD.

Critically, individual responsiveness to rTMS is variable, potentially reducing its effectiveness. Metaplasticity whereby the brain is preconditioned with a neuroelectric stimulus before the treating stimulus is administered is a potential way of reducing variability. Metaplasticity has recently been shown to improve responses within the swallowing motor system following cortical rTMS. However, to date no cerebellar rTMS study has applied this approach. This is a gap in our understanding which will need to be addressed.

The overarching aim of the study is to develop a less variable and more effective treatment for neurogenic dysphagia. More specifically the study objectives are to establish:

1. Whether 10Hz Cer-rTMS delivered over hemispheric pharyngeal areas can induce SMS metaplastic changes in healthy participants.
2. If a cerebellar rTMS metaplastic stimulation protocol can affect swallowing behaviour.

Study Overview

• Status: Not yet recruiting
• Conditions: Dysphagia; Swallowing
• Intervention / Treatment: Device: Cerebellar rTMS

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ayodele Sasegbon; Phone Number: 0161 789 7373; Email: ayodele.sasegbon@manchester.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Healthy participants > 18 years of age

Exclusion Criteria:

Exclusion criteria will be the presence or a history of:

1. Epilepsy
2. Cardiac pacemaker
3. Previous brain surgery
4. Previous swallowing problems
5. The use of medication which acts on the central nervous system
6. Any implanted metal in the head
7. Pregnancy (self-declared)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; 1. Real 10 Hz cerebellar rTMS (250 pulses) to the right cerebellar hemisphere immediately followed by 1 Hz cerebellar rTMS (600 pulses) to the same area. Pharyngeal motor evoked potential (PMEP) amplitude measured	Device: Cerebellar rTMS; Cerebellar rTMS applied to pharyngeal area of right hemisphere
Experimental: Arm 2; 2. Sham 10 Hz cerebellar rTMS (250 pulses) to the right cerebellar hemisphere immediately followed by 1 Hz cerebellar rTMS (600 pulses) to the same area. PMEP amplitude measured	Device: Cerebellar rTMS; Cerebellar rTMS applied to pharyngeal area of right hemisphere
Experimental: Arm 3; 3. Real 10 Hz cerebellar rTMS (250 pulses) to the right cerebellar hemisphere followed after 45 minutes by 1 Hz cerebellar rTMS (600 pulses) to the same area. PMEP amplitude measured	Device: Cerebellar rTMS; Cerebellar rTMS applied to pharyngeal area of right hemisphere
Experimental: Arm 4; 4. Real 10 Hz cerebellar rTMS (250 pulses) to the right cerebellar hemisphere followed after 90 minutes by 1 Hz cerebellar rTMS (600 pulses) to the same area. PMEP amplitude measured	Device: Cerebellar rTMS; Cerebellar rTMS applied to pharyngeal area of right hemisphere
Experimental: Arm 5; 5. Real 1 Hz cerebellar rTMS (600 pulses) to the right cerebellar hemisphere immediately followed by 10 Hz cerebellar rTMS (250 pulses) to the same area. PMEP amplitude measured	Device: Cerebellar rTMS; Cerebellar rTMS applied to pharyngeal area of right hemisphere
Experimental: Arm 6; 6. Sham 1 Hz cerebellar rTMS (600 pulses) to the right cerebellar hemisphere immediately followed by 10 Hz cerebellar rTMS (250 pulses) to the same area. PMEP amplitude measured	Device: Cerebellar rTMS; Cerebellar rTMS applied to pharyngeal area of right hemisphere
Experimental: Arm 7; 7. Real 1 Hz cerebellar rTMS (600 pulses) to the right cerebellar hemisphere followed after 30 minutes by 10 Hz cerebellar rTMS (250 pulses) to the same area. PMEP amplitude measured	Device: Cerebellar rTMS; Cerebellar rTMS applied to pharyngeal area of right hemisphere
Experimental: Arm 8; 8. Real 1 Hz cerebellar rTMS (600 pulses) to the right cerebellar hemisphere followed after 60 minutes by 10 Hz cerebellar rTMS (250 pulses) to the same area. PMEP amplitude measured	Device: Cerebellar rTMS; Cerebellar rTMS applied to pharyngeal area of right hemisphere
Experimental: Arm 9; Most excitatory metaplastic protocol (comparing effects of arms 1-8 against one another) to right cerebellar hemisphere. Swallowing accuracy measurements.	Device: Cerebellar rTMS; Cerebellar rTMS applied to pharyngeal area of right hemisphere
Experimental: Arm 10; Single dose cerebellar rTMS to right hemisphere. Swallowing accuracy measurements.	Device: Cerebellar rTMS; Cerebellar rTMS applied to pharyngeal area of right hemisphere

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharyngeal motor evoked potential (PMEP) amplitude	PMEP amplitude measured using single pulse transcranial magnetic stimulation over pharyngeal motor areas of the cortex and cerebellum	10 measurements made at baseline, 0 minutes post stimulation, 15 minutes post stimulation, 30 minutes post stimulation, 45 minutes post stimulation and 60 minutes post stimulation
Swallowing accuracy	Swallowing accuracy measured using a reaction time task	10 measurements made at baseline, 0 minutes post stimulation, 15 minutes post stimulation, 30 minutes post stimulation, 45 minutes post stimulation and 60 minutes post stimulation

Collaborators and Investigators

• Sponsor: University of Manchester
• Investigators: Principal Investigator: Ayodele Sasegbon, University of Manchester

Study record dates

Study Major Dates

• Study Start (Estimated): December 20, 2024
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: December 3, 2024
• First Submitted That Met QC Criteria: December 3, 2024
• First Posted (Estimated): December 6, 2024

Study Record Updates

• Last Update Posted (Estimated): December 6, 2024
• Last Update Submitted That Met QC Criteria: December 3, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Esophageal Diseases; Otorhinolaryngologic Diseases; Pharyngeal Diseases; Deglutition Disorders
• Other Study ID Numbers: 341596

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No identifiable data pertaining to individual participants will be shared with other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No