The Utility of Cerebellar Transcranial Magnetic Stimulation in the Neurorehabilitation of Dysphagia After Stroke

November 30, 2022 updated by: Prof Shaheen Hamdy PhD FRCP, University of Manchester

An Exploration of the Application of Non-invasive Cerebellar Stimulation in the Neurorehabilitation of Dysphagia After Stroke

The study is designed to explore the effectiveness of non-invasive cerebellar stimulation to enhance motor plasticity in the cortex after stroke. The investigators have shown that the human cerebellum is strongly activated during the act of swallowing and when stimulated with single TMS pulses can strongly facilitate the corticobulbar projection to the pharynx in humans. More recently the investigators have identified the most relevant frequency of stimulation of the cerebellum that can produce longer term excitation in the human swallowing motor system. The investigators therefore believe that the potential for cerebellar stimulation in improving swallowing is much greater than other methods for two reasons. Firstly, previous work has shown that unlike successful recovery of hand/arm function which relies on restoring activity in the stroke hemisphere, recovery of swallowing function relies on increased excitability in intact projections from the non-stroke hemisphere. The investigators believe that methods that can enhance these undamaged pathways have a greater chance of inducing recovery in the human swallowing system in unilateral stroke. Additionally cerebellar stimulation produces very high levels of corticobulbar excitation it may also have the advantage of improving dysphagia in posterior fossa strokes. Second, the human cerebellum is relatively easy to target and stimulate and has reduced risk of inducing unwanted effects (such as seizures) which as a consequence makes cerebellar stimulation a more pragmatic method for delivering therapeutic neurorehabilitation to dysphagic stroke patients compared to other more complex/riskier methods.

A final factor is that the investigators have developed a "virtual lesion" model of swallowing dysfunction in healthy volunteers which can be reversed quite successfully with other neuro-stimulation protocols. The investigators can therefore use this model to test the effectiveness of cerebellar stimulation protocols (ipsilateral and contralateral cerebellar sites) before choosing the most effective side to apply stimulation in a proof of principle trial/study in a small group of sub-acute dysphagic patients.

The hypotheses are that cerebellar TMS will:

i. Reverse the brain inhibition and behavioural dysfunction following a virtual lesion model of disrupted swallowing in healthy brain (phase 1); ii. Reduce the degree of aspiration in acute dysphagia after a stroke (phase 2).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Protocols:

Hypothesis 1:

Cortical excitability (in both dominant and non-dominant swallowing cortex) to TMS and swallowing behaviour assessed with a swallowing reaction time task will be measured at baseline. Thereafter, the virtual lesion paradigm will be applied to the dominant swallowing projection followed by the cerebellar intervention (10Hz, 250 pulses). Cerebellar stimulation will be applied (in a randomised fashion) on separate occasions to both the contralateral and ipsilateral cerebellar hemispheres, immediately after the virtual lesion. The investigators have found that placement using known reference landmarks are equivalent to using neuronavigation, so the latter will not be employed. Repeat measurements of cortical excitability and swallowing behaviour will then be performed and analysed against baseline data and a sham cerebellar paradigm. Differences in cortical excitability and swallowing responses will thus be an indication of which cerebellar region (contralesional/ipsilesional) can influence excitability and reverse any behavioural changes most effectively.

Hypothesis 2:

I. Dysphagic stroke patients (n=24) recruited over a 9 month period within 14 days of stroke ictus will have their swallowing assessed by videofluoroscopy before and after receiving either the real or sham cerebellar stimulation (10Hz, 250 pulses) as determined from phase 1. As before, placement of the coil for cerebellar stimulation will be performed using landmarks already established and validated in the work from question 1. Patients will be intubated with the pharyngeal EMG catheter for pre and post recordings of pharyngeal motor evoked potentials (MEPs) to cortical TMS. Power calculations, based on a similar study of pharyngeal stimulation indicated that the investigators would need 12 patients per group to achieve a statistical power of 80% at a 5% significance level to detect changes in the primary outcome measure of aspiration. In this study, the investigators will examine if the chosen site of cerebellar stimulation from phase 1 can induce short-term changes in brain function (pharyngeal MEPs) and swallowing function (videofluoroscopy) compared to sham interventions and baseline measurement, up to 1 hour after the intervention.

II. Following stage I, once it is established that cerebellar stimulation can alter brain and swallowing functions in stroke in the short-term, it will need to be appraised for clinical feasibility, dose response, and longer term efficacy. Dysphagic stroke patients (n=48, 16 patients per group) admitted to the stroke unit and identified by videofluoroscopy will be recruited over the next 21 months. Since it is not known how the cerebellar stimulation method should be delivered to patients, a dose ranging treatment trial will be utilised, randomising patients to one of three groups (A-C), low level stimulation, high level stimulation and sham stimulation. From our previous work with pharyngeal stimulation, the investigators propose that group A will receive stimulation once per day for 3 days. Group B will receive stimulation twice per day for 5 days. Group C will receive sham stimulation (delivered as in protocol I) twice a day for 5 days. Groups A and B will receive stimulation at the optimal site (10Hz, 250 pulses) found in question 1, but all groups will also receive standard speech and language therapy.

Assessments:

Swallowing before and after stimulation will be evaluated using videofluoroscopy, at 1 hour for protocol I. For protocol II the investigators propose both videofluoroscopy and functional scores (Functional oral ingestion scale (FOIS), the dysphagia severity rating scale (DSRS) including feeding status and modified rankin scale (mRS)) at baseline and at 2 weeks.

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Greater Manchester
      • Manchester, Greater Manchester, United Kingdom, M6 8HD
        • Upper G.I laboratory, Salford Royal Hospital
    • Notthinghamshire
      • Nottingham, Notthinghamshire, United Kingdom
        • Stroke Unit, Nottingham University Hospitals

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients aged 18 years and over
  • All patients with an acute anterior or posterior cerebral circulation stroke within 6 weeks of symptom onset.

Exclusion Criteria:

  • Advanced dementia
  • Previous history of dysphagia
  • Patients judged to be clinically unstable
  • Presence of implanted cardiac pacemaker or defibrillator
  • Any severe chronic medical condition that compromises cardiac or respiratory status
  • Patients with acute lower respiratory tract infections requiring antibiotic treatment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Hypothesis 2 Protocol 2 Low dose TMS
Low level cerebellar TMS. Delivered once per day for 3 days.
Device: Cerebellar TMS
Cerebellar transcranial magnetic stimulation
ACTIVE_COMPARATOR: Hypothesis 2 Protocol 2 High dose TMS
High level cerebellar TMS. Delivered twice per day for 5 days.
Device: Cerebellar TMS
Cerebellar transcranial magnetic stimulation
SHAM_COMPARATOR: Hypothesis 2 Protocol 2 Sham
Sham cerebellar TMS. Delivered twice a day for 5 days.
Device: Sham cerebellar TMS
Sham cerebellar transcranial magnetic stimulation
ACTIVE_COMPARATOR: Hypothesis 2 Protocol 1 Cerebellar TMS
Cerebellar TMS at 10Hz, 250 pulses.
Device: Cerebellar TMS
Cerebellar transcranial magnetic stimulation
SHAM_COMPARATOR: Hypothesis 2 Protocol 1 Sham
Sham cerebellar TMS
Device: Sham cerebellar TMS
Sham cerebellar transcranial magnetic stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Penetration aspiration scores on videofluoroscopy (number of swallows out of 6 that score 3 or more on the penetration aspiration scale) (Hypothesis 2 protocols 1 and 2)
Time Frame: 1 hour post intervention and 2 weeks post intervention
Penetration aspiration scores on videofluoroscopy (number of swallows out of 6 that score 3 or more on the penetration aspiration scale)
1 hour post intervention and 2 weeks post intervention

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Improvement of: Functional oral ingestion scale (FOIS) and or the dysphagia severity rating scale (DSRS) (Hypothesis 2 protocol 2)
Time Frame: 2 weeks post intervention
Improvement of: Functional oral ingestion scale (FOIS) and or the dysphagia severity rating scale (DSRS)
2 weeks post intervention

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Manchester

Collaborators

University of Nottingham
Medical Research Council

Investigators

  • Principal Investigator: Shaheen Hamdy, MBChB, PhD, University of Manchester

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

January 14, 2019

Primary Completion (ACTUAL)

June 30, 2022

Study Completion (ACTUAL)

October 31, 2022

Study Registration Dates

First Submitted

August 14, 2017

First Submitted That Met QC Criteria

September 4, 2017

First Posted (ACTUAL)

September 7, 2017

Study Record Updates

Last Update Posted (ACTUAL)

December 1, 2022

Last Update Submitted That Met QC Criteria

November 30, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 5111 protocol ver1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

No identifiable individual participant information will be shared outside the immediate research team. However, identifiable individual participant information will be made available to the Medical research council and the University of Manchester if required for the purposes of auditing the study.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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