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

NCT03274947 | Completed DMC

• 1 other identifier: 5111 protocol ver1
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

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).

Conditions

Oropharyngeal Dysphagia; Stroke

Keywords

Oropharyngeal Dysphagia; Stroke

Outcome Measures

Primary Outcomes (1)

• 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)

  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 Outcomes (1)

• Improvement of: Functional oral ingestion scale (FOIS) and or the dysphagia severity rating scale (DSRS) (Hypothesis 2 protocol 2)

  2 weeks post intervention

Study Arms (5)

Hypothesis 2 Protocol 2 Low dose TMS

ACTIVE COMPARATOR

Low level cerebellar TMS. Delivered once per day for 3 days.

Device: Cerebellar TMS

Hypothesis 2 Protocol 2 High dose TMS

ACTIVE COMPARATOR

High level cerebellar TMS. Delivered twice per day for 5 days.

Device: Cerebellar TMS

Hypothesis 2 Protocol 2 Sham

SHAM COMPARATOR

Sham cerebellar TMS. Delivered twice a day for 5 days.

Device: Sham cerebellar TMS

Hypothesis 2 Protocol 1 Cerebellar TMS

ACTIVE COMPARATOR

Cerebellar TMS at 10Hz, 250 pulses.

Device: Cerebellar TMS

Hypothesis 2 Protocol 1 Sham

SHAM COMPARATOR

Sham cerebellar TMS

Device: Sham cerebellar TMS

Interventions

Cerebellar TMS DEVICE

Cerebellar transcranial magnetic stimulation

Hypothesis 2 Protocol 1 Cerebellar TMS; Hypothesis 2 Protocol 2 High dose TMS; Hypothesis 2 Protocol 2 Low dose TMS

Sham cerebellar TMS DEVICE

Sham cerebellar transcranial magnetic stimulation

Hypothesis 2 Protocol 1 Sham; Hypothesis 2 Protocol 2 Sham

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Manchester: lead
• Medical Research Council: collaborator
• University of Nottingham: collaborator

Study Sites (2)

Upper G.I laboratory, Salford Royal Hospital

Manchester, Greater Manchester, M6 8HD, United Kingdom

Location

Stroke Unit, Nottingham University Hospitals

Nottingham, Notthinghamshire, United Kingdom

Location

Related Publications (22)

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• Hamdy S, Aziz Q, Rothwell JC, Power M, Singh KD, Nicholson DA, Tallis RC, Thompson DG. Recovery of swallowing after dysphagic stroke relates to functional reorganization in the intact motor cortex. Gastroenterology. 1998 Nov;115(5):1104-12. doi: 10.1016/s0016-5085(98)70081-2.

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• Jefferson S, Mistry S, Michou E, Singh S, Rothwell JC, Hamdy S. Reversal of a virtual lesion in human pharyngeal motor cortex by high frequency contralesional brain stimulation. Gastroenterology. 2009 Sep;137(3):841-9, 849.e1. doi: 10.1053/j.gastro.2009.04.056. Epub 2009 May 7.

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• Jayasekeran V, Singh S, Tyrrell P, Michou E, Jefferson S, Mistry S, Gamble E, Rothwell J, Thompson D, Hamdy S. Adjunctive functional pharyngeal electrical stimulation reverses swallowing disability after brain lesions. Gastroenterology. 2010 May;138(5):1737-46. doi: 10.1053/j.gastro.2010.01.052. Epub 2010 Feb 2.

  PMID: 20138037 BACKGROUND

• Vasant DH, Mistry S, Michou E, Jefferson S, Rothwell JC, Hamdy S. Transcranial direct current stimulation reverses neurophysiological and behavioural effects of focal inhibition of human pharyngeal motor cortex on swallowing. J Physiol. 2014 Feb 15;592(4):695-709. doi: 10.1113/jphysiol.2013.263475. Epub 2013 Nov 18.

  PMID: 24247983 BACKGROUND

MeSH Terms

Conditions

Deglutition Disorders; Stroke

Condition Hierarchy (Ancestors)

Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Pharyngeal Diseases; Otorhinolaryngologic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Shaheen Hamdy, MBChB, PhD

  University of Manchester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 14, 2017
• First Posted: September 7, 2017
• Study Start: January 14, 2019
• Primary Completion: June 30, 2022
• Study Completion: October 31, 2022
• Last Updated: December 1, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)