Sensory Neuromodulation Protocol for the Treatment of Post-stroke Oropharyngeal Dysphagia. (FIS2014)

Sensory Neuromodulation Protocol for the Treatment of Post-stroke Oropharyngeal Dysphagia. Short-term Neurophysiological Effects.

Study design: Multicenter, experimental, randomized, crossed, double blind study (patient and results analysis).

Aim: To evaluate the effect of different neurostimulation techniques on the neurophysiological and biomechanical swallowing mechanisms of patients with dysphagia associated with chronic stroke and select those techniques with the best results to be evaluated in the second phase of the study (medium-term effects).

Outcome measures:

• Videofluoroscopy: prevalence of impaired efficacy and safety of swallow (penetrations and aspirations), penetration aspiration scale (PAS: from 0 to 8), biomechanical parameters (time to laryngeal vestibule closure, upper esophageal sphincter opening).
• Pharyngeal sensory evoked potentials (pSEP): latency and amplitude of obtained evoked potentials. Higher latency (0 onwards) means worse outcome and higher amplitude (0 onwards) means better outcome.
• Pharyngeal motor evoked potentials (pMEP): latency, amplitude, duration and area of obtained evoked potentials. Higher latency (0 onwards) means worse outcome and higher amplitude (0 onwards) means better outcome.

Treatments and patients: 36 post-stroke patients with oropharyngeal dysphagia (PAS superior or equal to 2) randomized patients in 3 treatment arms (3 groups of 12 patients).

• Active and sham repetitive transcranial magnetic stimulation (rTMS): 90% of the resting motor threshold, 1250 pulses, 5 Hz.
• Active and sham Intrapharyngeal Electrical Stimulation (PES): 75% of tolerance threshold, pulses of 0.2 ms, 5 Hz, 10 min.
• Oral Capsaicin (active intervention, 10-5M, TRPV1 agonist) and placebo solution (sham): 100 mL, single administration.

Administration of study therapies:

The study will be performed in two visits separated for one week. In each visit patients will randomly receive active or sham treatment and a pre-post evaluation of biomechanics of deglutition (with VFS) and neurophysiological mechanisms (swallowing afferent and efferent pathways) will be performed in each visit.

Acute randomized administration -> 1 active session (pre/post evaluation with VFS/pSEP/pMEP) + 1 separate control session 1 week apart (pre/post evaluation with VFS/pSEP/pMEP).

Study Overview

• Status: Completed
• Conditions: Stroke; Dysphagia; Swallowing Disorder; Neurophysiologic Abnormality
• Intervention / Treatment: Device: rTMS active and sham; Device: PES active and sham; Dietary supplement: Capsaicin active and placebo

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients older than 18 years.
• Patients with a diagnosis of stroke of more than 3 months of evolution.
• Patients with clinical signs of dysphagia according to the volume viscosity swallowing test (V-VST).
• Patients capable of complying with the study protocol.
• Explained study and signed informed consent.

Exclusion Criteria:

• History of severe neurodegenerative, digestive diseases, epilepsy or previous seizures.
• Pacemaker or implanted defibrillator carriers.
• Implanted electrode carriers or other stimulation systems.
• Implant carriers or metal plates on the head or neck.
• Cochlear implant carriers.
• Medication pump carriers.
• History of hearing loss associated with noise.
• Cardiopulmonary instability.
• Oropharyngeal dysphagia of structural causes.
• History of head and neck surgery.
• Alcohol or drug dependence.
• Pregnancy or breastfeeding.
• Participate or have participated in another clinical interventionist trial in the 4 weeks prior to inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Repetitive transcranial magnetic stimulation (rtMS); Acute repetitive transcranial magnetic stimulation on the pharyngeal sensory cortex. Applied intensity 90% of the resting motor threshold, 1250 pulses at 5 Hz. Each treatment arm was placebo/sham compared with a time separation of one week. The assignment to either active or sham was randomized.	Device: rTMS active and sham; Repetitive transcranial magnetic stimulation of the pharyngeal sensory cortex.; Other Names: Repetitive transcranial magnetic stimulation
Active Comparator: Intrapharyngeal electrical stimulation (PES); Intrapharyngeal electrical stimulation applied to an intensity of 75% of the tolerance threshold with 0.2 ms pulses at 5 Hz during 10 min. Each treatment arm was placebo/sham compared with a time separation of one week. The assignment to either active or sham was randomized.	Device: PES active and sham; Intrapharyngeal electrical stimulation with a catheter delivering electrical pulses.; Other Names: Intrapharyngeal electrical stimulation
Active Comparator: Capsaicin; 100 mL of oral capsaicin solution at a concentration of 10-5M. Each treatment arm was placebo/sham compared with a time separation of one week. The assignment to either active or sham was randomized	Dietary supplement: Capsaicin active and placebo; Capsaicin solution (TRPV1 agonist) at a concentration of 10-5M or placebo solution.; Other Names: TRPV1 agonist (capsaicin at 10-5M) or placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharyngeal motor evoked potential (pMEP): latency and amplitude	Study the magnitude of the effect by calculating the change of the evoked potential from baseline immediately after the application of the intervention produced by the different treatments. This will be examined and compared between active and sham intervention.	The event wil be assessed with pMEP immediately after the application of the intervention (time frame maximum up to 2 hours).
Pharyngeal sensory evoked potential (pSEP): latency and amplitude	Study the magnitude of the effect by calculating the change of the evoked potential from baseline immediately after the application of the intervention produced by the different treatments. This will be examined and compared between active and sham intervention.	The event wil be assessed with pSEPs immediately after the application of the intervention (time frame maximum up to 2 hours).
Penetration-aspiration scale (PAS) score	Study the magnitude of the effect by calculating the change on the prevalence of unsafe swallow (PAS≥2) in videofluoroscopy (VFS) from baseline immediately after the application of the intervention. This will be examined and compared between active and sham intervention.	The event wil be assessed with the PAS score immediately after the application of the intervention (time frame maximum up to 2 hours from first assessment).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Opening and closing time of the laryngeal vestibule	Time of the laryngeal vestibule opening and closure ranges from 0 to 1000 ms.	The event wil be assessed with VFS immediately after the application of the intervention (time frame maximum up to 2 hours from first assessment).
Prevalence of pharyngeal residue	The presence of pharyngeal residue in individual subjects will be assessed.	The event will be assessed with VFS immediately after the application of the intervention (time frame maximum up to 2 hours from first assessment).
Resting motor threshold (RMT) of the pharyngeal cortex	RMT is defined as the stimulation intensity in which the half of the stimuli are able to evoke a motor evoked potential of al least 10 uV of amplitude.	The event wil be assessed with TMS immediately after the application of the intervention (time frame maximum up to 2 hours from first assessment).
Pharyngeal sensory thresholds	First perception and tolerance thresholds (from 0 to 100 mA) to electrical stimulation of the pharynx will be assessed by asking subjects the exact moment of first perception of the stimulus and the moment in which stimulation is not further tolerated, respectively.	The event wil be assessed with pharyngeal electrical stimulation immediately after the application of the intervention (time frame maximum up to 2 hours from first assessment).
Incidence of Treatment-Emergent Adverse Events	Seizures are the most feared side effect associated with transcranial magnetic stimulation (TMS). Seizures are a rare side event during and/or subsequent to a TMS session (1.4%, Bae et al., 2007) commonly not occurring beyond a few days after the last session. No other major or significant side effects are expected associated with the interventions.	Although its occurrence is early after the TMS session, seizures and other side effects will be monitored up to 3 months after the intervention.

Collaborators and Investigators

• Sponsor: Hospital de Mataró
• Investigators: Principal Investigator: Pere Clavé, PhD, Hospital de Mataro

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2016
• Primary Completion (Actual): December 21, 2018
• Study Completion (Actual): December 21, 2018

Study Registration Dates

• First Submitted: August 2, 2019
• First Submitted That Met QC Criteria: August 8, 2019
• First Posted (Actual): August 9, 2019

Study Record Updates

• Last Update Posted (Actual): August 13, 2019
• Last Update Submitted That Met QC Criteria: August 9, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Stroke; Oropharyngeal dysphagia; Sensory stimulation
• Additional Relevant MeSH Terms: Digestive System Diseases; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Gastrointestinal Diseases; Pharyngeal Diseases; Otorhinolaryngologic Diseases; Esophageal Diseases; Stroke; Deglutition Disorders; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Dermatologic Agents; Antipruritics; Capsaicin
• Other Study ID Numbers: FIS2014

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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