Aftereffects of PES Preconditioned with RTMS on the Human Pharyngeal Motor Cortex

NCT ID: NCT06884488

Last Updated: 2025-03-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-14
• Study Completion Date: 2025-08-31

Brief Summary

The goal of this interventional study is to optimize the excitatory brain effects of combined neuromodulatory therapies on swallowing areas of the brain. The main question it aims to answer is:

Does preconditioning with 1 Hertz (Hz) repetitive transcranial magnetic stimulation (rTMS) delivered over hemispheric pharyngeal areas enhance the activating effects of pharyngeal electrical stimulation (PES) on cortical excitability?

Participants will:

• Visit the department three times, with at least a one-week gap between visits.
• Undergo baseline measurements for Pharyngeal motor evoked potential (PMEP) and Thenar motor evoked potential (TMEP), involving an electromyography (EMG) pharyngeal catheter inserted into the pharynx and gel electrodes to detect muscle activity.
• Be randomly allocated to one of the three preconditioning-conditioning procedures during each visit : 1Hz rTMS followed by 5Hz PES, sham 1Hz rTMS followed by 5Hz PES, and 1Hz rTMS followed by sham 5Hz PES

1. Real rTMS will involve a figure-of-eight coil flat against the head delivering 1Hz stimulation at 90% of the thenar resting motor threshold.

2. Sham rTMS will involve holding the coil perpendicular to the scalp to prevent brain stimulation.

3. PES will involve a catheter delivering 0.2-ms pulses at 5Hz and 75% of the maximal tolerated intensity for 10 minutes. Sham PES will involve deactivating the current generator.

• Complete PMEP and TMEP measurements at baseline before intervention and every 15 minutes from 0 - 60 minutes after the rTMS-PES procedure.
• Complete a survey regarding tolerability and safety at the end of each visit.

Detailed Description

1 Study design This is a cross-over study with the order of experimental conditions randomized for each participant. The randomisation will be conducted using a randomisation program (Stats Direct, v2.7.8, StatsDirect Ltd, Altrincham, UK). Each condition will be given on separate days, at least one week apart.

2. Participants Healthy volunteers over the age of 18 will be recruited through adverts placed around Salford Royal Hospital, on a University of Manchester website which advertises for research volunteers and through a departmental database of volunteers who have expressed an interest in future research.

3. Informed consent A participant information sheet will be given to each participant. A researcher with up-to-date Good Clinical Practice (GCP) training will be responsible for obtaining consent from the participants. He/she will explain the study purpose and nature and experimental procedures verbally to the participants. The participants will be given sufficient time (at least 24 hours) to read and digest the written information and discuss with the researcher about the study. The researcher will ensure the participants are volunteering to participate, understand the purpose and nature, experimental procedures, benefits and risks of the study before obtaining written consent from them. The participants should understand that they have the rights to withdraw from the study anytime throughout the study.

4. Study Procedures

Participants will undergo either active or sham preconditioned 1 Hz rTMS interventions with 30 min intervals before active or sham 5 Hz PES (Fig 1). Each session involved:

1. A baseline measurement of PMEP and TMEP.

2. Application of (active/sham) 1 Hz rTMS (preconditioning).

3. A resting interval (30 minutes).

4. Application of (active/sham) 5 Hz PES (conditioning).

5. Measurement of PMEP and TMEP at multiple time points (immediately, 15, 30, 45, and 60 minutes post-PES).

5. End of study The study will come to an end after the period of data collection and analysis by the end of August 2025.

6. Withdraw consent Participants are able to withdraw consent at any time they wish. This will be stressed to all participants by members of the research team. Should this happen, their data will be retained with permission from the subject and they will be removed from the study.

As only healthy participants will be recruited for this study, no participant is expected to lose the capacity to consent during the course of the study. However, if for any reason a loss of capacity is suspected, the participant will be excluded from the study.

Conditions

Healthy Subjects (HS)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

real rTMS + real PES

Participants will receive real 1Hz rTMS over the dominant hemisphere, followed by a 30min interval. After that the participants will receive real 5Hz PES.

Group Type: EXPERIMENTAL

repetitive transcranial magnetic stimulation (Magstim Super Rapid stimulator, The Magstim Company Ltd, Whitland, UK)

Intervention Type: DEVICE

The paradigm will be applied over the dominant cerebral hemisphere for 10 minutes (600 pulses) over the dominant pharyngeal motor cortex capped at 120% of pharyngeal resting motor threshold.

pharyngeal electrical stimulation (Digitimer model DS7; Welwyn-Garden City, Herts, UK)

Intervention Type: DEVICE

The PES (0.2-ms pulses, 280 V) was delivered at a set frequency (5 Hz), intensity (75% of maximal tolerated), and duration (10 minutes), which have been reported as the most effective parameters for PES.

sham rTMS + real PES

Participants will receive sham 1Hz rTMS over the dominant hemisphere, followed by a 30min interval. After that the participants will receive real 5Hz PES.

Group Type: SHAM_COMPARATOR

pharyngeal electrical stimulation (Digitimer model DS7; Welwyn-Garden City, Herts, UK)

Intervention Type: DEVICE

The PES (0.2-ms pulses, 280 V) was delivered at a set frequency (5 Hz), intensity (75% of maximal tolerated), and duration (10 minutes), which have been reported as the most effective parameters for PES.

sham repetitive transcranial magnetic stimulation(Magstim Super Rapid stimulator, The Magstim Company Ltd, Whitland, UK)

Intervention Type: DEVICE

Sham rTMS is delivered with the coil tilted to its side at 90 degrees and with the identical stimulation conditions as active 1 Hz rTMS.

real rTMS + sham PES

Participants will receive real 1Hz rTMS over the dominant hemisphere, followed by a 30min interval. After that the participants will receive sham 5Hz PES.

Group Type: SHAM_COMPARATOR

repetitive transcranial magnetic stimulation (Magstim Super Rapid stimulator, The Magstim Company Ltd, Whitland, UK)

Intervention Type: DEVICE

The paradigm will be applied over the dominant cerebral hemisphere for 10 minutes (600 pulses) over the dominant pharyngeal motor cortex capped at 120% of pharyngeal resting motor threshold.

sham pharyngeal electrical stimulation (Digitimer model DS7; Welwyn-Garden City, Herts, UK)

Intervention Type: DEVICE

For sham pharyngeal stimulation, the same method including the insertion of the catherter will be employed without actual electrical stimulation.

Interventions

repetitive transcranial magnetic stimulation (Magstim Super Rapid stimulator, The Magstim Company Ltd, Whitland, UK)

The paradigm will be applied over the dominant cerebral hemisphere for 10 minutes (600 pulses) over the dominant pharyngeal motor cortex capped at 120% of pharyngeal resting motor threshold.

Intervention Type: DEVICE

pharyngeal electrical stimulation (Digitimer model DS7; Welwyn-Garden City, Herts, UK)

The PES (0.2-ms pulses, 280 V) was delivered at a set frequency (5 Hz), intensity (75% of maximal tolerated), and duration (10 minutes), which have been reported as the most effective parameters for PES.

Intervention Type: DEVICE

sham repetitive transcranial magnetic stimulation(Magstim Super Rapid stimulator, The Magstim Company Ltd, Whitland, UK)

Sham rTMS is delivered with the coil tilted to its side at 90 degrees and with the identical stimulation conditions as active 1 Hz rTMS.

Intervention Type: DEVICE

sham pharyngeal electrical stimulation (Digitimer model DS7; Welwyn-Garden City, Herts, UK)

For sham pharyngeal stimulation, the same method including the insertion of the catherter will be employed without actual electrical stimulation.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

Healthy volunteers over the age of 18 will be recruited through adverts placed around Salford Royal Hospital, on a University of Manchester website which advertises for research volunteers and through a departmental database of volunteers who have expressed an interest in future research. There is no upper age limit for potential participants.

Exclusion Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Manchester

OTHER

Sponsor Role: lead

Responsible Party

Prof Shaheen Hamdy PhD FRCP

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Shaheen Hamdy, PhD

Role: PRINCIPAL_INVESTIGATOR

The University of Manchester

Locations

University of Manchester

Manchester, , United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

Meng Dai, PhD

Role: CONTACT

meng.dai@manchester.ac.uk

44 7585922413

Ayodele Sasegbon, PhD

Role: CONTACT

Facility Contacts

Shaheen Professor Hamdy, PhD

Role: primary

shaheen.hamdy@manchester.ac.uk

44 07973665987

Other Identifiers

2024-20990-37010

Identifier Type: -

Identifier Source: org_study_id