Treatment of Chronic Post-stroke Oropharyngeal Dysphagia With Paired Stimulation

NCT05720871 | Unknown

• 1 other identifier: STROD_ICI_C
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

According WHO, oropharyngeal dysphagia (OD) is a prevalent post-stroke (PS) condition involving the digestive system (ICD-10: I69.391) and an independent risk factor for malnutrition and pulmonary infection; and leads to greater morbimortality and healthcare costs and poorer quality of life (QoL). Currently, OD therapy is mainly compensatory, with low rates of compliance and small benefit, and there is no pharmacological treatment, so new treatments that improve patients' condition are crucial. PS-OD patients present both oropharyngeal sensory and motor deficits, so neurorehabilitation treatments which target both could be optimum. Benefits of paired peripheral sensory stimulation with oral capsaicin and of central motor noninvasive brain stimulation techniques such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) will be studied. Pairing pharmacological peripheral and central stimulation may produce greater benefits. The main aim of the project is to study the efficacy of two novel protocols of paired stimulation on PS-OD patients. The investigators will assess whether 5-day application of tDCS/capsaicin or rTMS/capsaicin in the chronic phase of stroke, will improve PS-OD. One RCT (200 patients in the chronic stroke phase divided in 4 study arms) will assess changes in swallow safety, biomechanics and neurophysiology of the swallow response, hospital stay, respiratory and nutritional complications, mortality and QoL.

Conditions

Oropharyngeal Dysphagia; Stroke; Stroke, Complication; Swallowing Disorder

Keywords

Non-Invasive Brain Stimulation; Sensory Stimulation; Transcranial Magnetic Stimulation; Transcranial Direct Current Stimulation; TRPV1 agonists; Capsaicin

Outcome Measures

Primary Outcomes (11)

• Changes in the videofluoroscopy (signs of safety and efficacy of swallow)

  Pre- vs post-intervention changes in: \- Frequency of videofluoroscopic (VFS) signs of safety and efficacy of swallow.

  5 days (changes between basal visit, time 0, and post-treatment visit, time + 5 days)

• Changes in the videofluoroscopy (Penetration-Aspiration scale)

  Pre- vs post-intervention changes in: \- Penetration-Aspiration scale (PAS). The scales goes from 1 (safe swallow) to 8 (silent aspiration). The severity increases as the score increases.

  5 days (changes between basal visit, time 0, and post-treatment visit, time + 5 days)

• Timing of oropharyngeal swallow response (total deglutition time) with videofluoroscopy

  \- Total deglutition time (ms).

  5 days (changes between basal visit, time 0, and post-treatment visit, time + 5 days)

• Timing of oropharyngeal swallow response (time to laryngeal vestibule closure) with videofluoroscopy

  \- Time to laryngeal vestibule closure (ms).

  5 days (changes between basal visit, time 0, and post-treatment visit, time + 5 days)

• Timing of oropharyngeal swallow response (time to upper esophageal sphincter opening) with videofluoroscopy

  \- Time to upper esophageal sphincter opening (ms).

  5 days (changes between basal visit, time 0, and post-treatment visit, time + 5 days)

• Timing of oropharyngeal swallow response (bolus velocity) with videofluoroscopy

  \- Bolus velocity (m·s-1).

  5 days (changes between basal visit, time 0, and post-treatment visit, time + 5 days)

• Timing of oropharyngeal swallow response (Kinetic energy) with videofluoroscopy

  \- Kinetic energy of the bolus (mJ).

  5 days (changes between basal visit, time 0, and post-treatment visit, time + 5 days)

• Changes in neurophysiology of swallow (sensory pathway) latency

  \- Latency of pharyngeal sensory evoked potentials to intrapharyngeal electrical stimulation.

  5 days (changes between basal visit, time 0, and post-treatment visit, time + 5 days)

• Changes in neurophysiology of swallow (sensory pathway) amplitude

  \- Amplitude of pharyngeal sensory evoked potentials to intrapharyngeal electrical stimulation.

  5 days (changes between basal visit, time 0, and post-treatment visit, time + 5 days)

• Changes in neurophysiology of swallow (motor pathway) latency

  \- Latency of pharyngeal motor evoked potentials to transcranial magnetic stimulation.

  5 days (changes between basal visit, time 0, and post-treatment visit, time + 5 days)

• Changes in neurophysiology of swallow (motor pathway) amplitude

  \- Amplitude of pharyngeal motor evoked potentials to transcranial magnetic stimulation.

  5 days (changes between basal visit, time 0, and post-treatment visit, time + 5 days)

Secondary Outcomes (10)

• Changes in spontaneous swallowing frequency

  5 days (changes between basal visit, time 0, and post-treatment visit, time + 5 days)

• Safety of the treatment

  Baseline (basal visit) to 3 months follow-up

• Length of stay

  Baseline (basal visit) to 3 months follow-up

• Aspiration pneumonia admission

  Baseline (basal visit) to 3 months follow-up

• Nutritional status

  Baseline (basal visit) to 3 months follow-up

Study Arms (4)

Active rTMS + capsaicin 150μM

EXPERIMENTAL

Each session (5 consecutive days) of active treatment consists of swallowing 10mL capsaicin (150μM) and, just after, of applying focal (alpha D70 coil) rTMS (Magstim Rapid2, UK) over the pharyngeal M1 hotspot of the unaffected hemisphere.

Device: rTMS + capsaicin 150μM (natural TRPV1 agonist)

sham rTMS + placebo

OTHER

The same protocol will be applied, swallowing 10mL of placebo (potassium sorbate) but with the coil tilted 90º from the tangent of the skull, as a standard method for sham rTMS application.

Device: rTMS + capsaicin 150μM (natural TRPV1 agonist)

active tDCS + capsaicin 150μM

EXPERIMENTAL

Active treatment consists of swallowing 10mL capsaicin (150μM) and, just after, of applying 30min of 2.0mA tDCS (DC-Stimulator Plus, NeuroConn, Germany) with the anode placed over the pharyngeal primary motor cortex (M1) of the unaffected hemisphere (3.5cm lateral / 1cm anterior to the vertex) and the cathode over the opposite supraorbital region.

Device: tDCS + capsaicin 150μM (natural TRPV1 agonist)

sham tDCS + placebo

OTHER

The same protocol will be applied, swallowing 10mL of placebo (potassium sorbate) but tDCS current is ramped up over 30s in order to simulate the active tDCS and then turned off for 30min23. Setup characteristics otherwise invariable.

Device: tDCS + capsaicin 150μM (natural TRPV1 agonist)

Interventions

rTMS + capsaicin 150μM (natural TRPV1 agonist) DEVICE

Repetitive transcranial magnetic stimulation (non-invasive brain stimulation) + Capsaicin. 5 consecutive days of active treatment consists of swallowing 10mL capsaicin (150μM) and, just after, of applying focal (alpha D70 coil) rTMS (Magstim Rapid2, UK) over the pharyngeal M1 hotspot of the unaffected hemisphere. A total of 500 pulses/session are delivered consisting of 10 5Hz-trains of 10s of 50 pulses each (total 2500 pulses), with a 1min interval between trains at an intensity of 90% of the resting motor threshold (RMT). The intervention has its respective sham rTMS+placebo group that is also applied over 5 consecutive days.

Also known as: Repetitive transcranial magnetic stimulation (rTMS) (MagStim, UK) + TRPV1 natural agonist capsaicin at 150μM

Active rTMS + capsaicin 150μM; sham rTMS + placebo

tDCS + capsaicin 150μM (natural TRPV1 agonist) DEVICE

Transcranial direct current stimulation (non-invasive brain stimulation) + Capsaicin. Treatment consists of swallowing 10mL capsaicin (150μM) and, just after, of applying 30min of 2.0mA tDCS (DC-Stimulator Plus, NeuroConn, Germany) with the anode placed over the pharyngeal primary motor cortex (M1) of the unaffected hemisphere (3.5cm lateral / 1cm anterior to the vertex) and the cathode over the opposite supraorbital region. The intervention has its respective sham tDCS+placebo group that is also applied over 5 consecutive days.

Also known as: Transcranial direct current stimulation (tDCS) (Neuroconn, Germany) + TRPV1 natural agonist capsaicin at 150μM

active tDCS + capsaicin 150μM; sham tDCS + placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chronic (\>3 and \<24 months) unilateral hemispheric stroke adult patients.
• Patients with impaired safety of swallow with a penetration-aspiration score (PAS) ≥ 2 with videofluoroscopy (VFS).
• Patient able to follow the study protocol and give the written informed consent.

You may not qualify if:

• Pregnancy.
• Life expectancy less than 3m or palliative care.
• Neurodegenerative disorder.
• Previously diagnosed oropharyngeal dysphagia (dysphagia not related to stroke).
• Implanted electronic device.
• Epilepsy.
• Metal in the head.
• Participation in another clinical trial in the previous month.

Sponsors & Collaborators

• Hospital de Mataró: lead
• Consorci Sanitari del Maresme: collaborator
• Instituto de Salud Carlos III: collaborator

Study Sites (1)

Hospital de Mataró. Consorci Sanitari del Mareme.

Mataró, Barcelona, 08304, Spain

RECRUITING

Related Publications (12)

• Cabib C, Ortega O, Kumru H, Palomeras E, Vilardell N, Alvarez-Berdugo D, Muriana D, Rofes L, Terre R, Mearin F, Clave P. Neurorehabilitation strategies for poststroke oropharyngeal dysphagia: from compensation to the recovery of swallowing function. Ann N Y Acad Sci. 2016 Sep;1380(1):121-138. doi: 10.1111/nyas.13135. Epub 2016 Jul 11.

  PMID: 27398981 RESULT

• Cabib C, Nascimento W, Rofes L, Arreola V, Tomsen N, Mundet L, Palomeras E, Michou E, Clave P, Ortega O. Short-term neurophysiological effects of sensory pathway neurorehabilitation strategies on chronic poststroke oropharyngeal dysphagia. Neurogastroenterol Motil. 2020 Sep;32(9):e13887. doi: 10.1111/nmo.13887. Epub 2020 May 24.

  PMID: 32449296 RESULT

• Cabib C, Nascimento W, Rofes L, Arreola V, Tomsen N, Mundet L, Muriana D, Palomeras E, Michou E, Clave P, Ortega O. Neurophysiological and Biomechanical Evaluation of the Mechanisms Which Impair Safety of Swallow in Chronic Post-stroke Patients. Transl Stroke Res. 2020 Feb;11(1):16-28. doi: 10.1007/s12975-019-00701-2. Epub 2019 Apr 2.

  PMID: 30941716 RESULT

• Cabib C, Ortega O, Vilardell N, Mundet L, Clave P, Rofes L. Chronic post-stroke oropharyngeal dysphagia is associated with impaired cortical activation to pharyngeal sensory inputs. Eur J Neurol. 2017 Nov;24(11):1355-1362. doi: 10.1111/ene.13392. Epub 2017 Sep 5.

  PMID: 28872738 RESULT

• Nascimento W, Tomsen N, Acedo S, Campos-Alcantara C, Cabib C, Alvarez-Larruy M, Clave P. Effect of Aging, Gender and Sensory Stimulation of TRPV1 Receptors with Capsaicin on Spontaneous Swallowing Frequency in Patients with Oropharyngeal Dysphagia: A Proof-of-Concept Study. Diagnostics (Basel). 2021 Mar 7;11(3):461. doi: 10.3390/diagnostics11030461.

  PMID: 33799960 RESULT

• Wang Z, Wu L, Fang Q, Shen M, Zhang L, Liu X. Effects of capsaicin on swallowing function in stroke patients with dysphagia: A randomized controlled trial. J Stroke Cerebrovasc Dis. 2019 Jun;28(6):1744-1751. doi: 10.1016/j.jstrokecerebrovasdis.2019.02.008. Epub 2019 Apr 5.

  PMID: 30956054 RESULT

• Tomsen N, Ortega O, Alvarez-Berdugo D, Rofes L, Clave P. A Comparative Study on the Effect of Acute Pharyngeal Stimulation with TRP Agonists on the Biomechanics and Neurophysiology of Swallow Response in Patients with Oropharyngeal Dysphagia. Int J Mol Sci. 2022 Sep 15;23(18):10773. doi: 10.3390/ijms231810773.

  PMID: 36142680 RESULT

• Tomsen N, Ortega O, Rofes L, Arreola V, Martin A, Mundet L, Clave P. Acute and subacute effects of oropharyngeal sensory stimulation with TRPV1 agonists in older patients with oropharyngeal dysphagia: a biomechanical and neurophysiological randomized pilot study. Therap Adv Gastroenterol. 2019 Apr 30;12:1756284819842043. doi: 10.1177/1756284819842043. eCollection 2019.

  PMID: 31068978 RESULT

• Hamdy S, Aziz Q, Rothwell JC, Crone R, Hughes D, Tallis RC, Thompson DG. Explaining oropharyngeal dysphagia after unilateral hemispheric stroke. Lancet. 1997 Sep 6;350(9079):686-92. doi: 10.1016/S0140-6736(97)02068-0.

  PMID: 9291902 RESULT

• Kumar S, Wagner CW, Frayne C, Zhu L, Selim M, Feng W, Schlaug G. Noninvasive brain stimulation may improve stroke-related dysphagia: a pilot study. Stroke. 2011 Apr;42(4):1035-40. doi: 10.1161/STROKEAHA.110.602128. Epub 2011 Mar 24.

  PMID: 21441148 RESULT

• Park JW, Oh JC, Lee JW, Yeo JS, Ryu KH. The effect of 5Hz high-frequency rTMS over contralesional pharyngeal motor cortex in post-stroke oropharyngeal dysphagia: a randomized controlled study. Neurogastroenterol Motil. 2013 Apr;25(4):324-e250. doi: 10.1111/nmo.12063. Epub 2012 Dec 23.

  PMID: 23279198 RESULT

• Kobayashi M, Pascual-Leone A. Transcranial magnetic stimulation in neurology. Lancet Neurol. 2003 Mar;2(3):145-56. doi: 10.1016/s1474-4422(03)00321-1.

  PMID: 12849236 RESULT

MeSH Terms

Conditions

Deglutition Disorders; Stroke

Interventions

Transcranial Magnetic Stimulation; Transcranial Direct Current Stimulation

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

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics; Electric Stimulation Therapy; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Study Officials

• Pere Clavé, MD, PhD

  Consorci Sanitari del Maresme

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pere Clavé, MD, PhD

CONTACT

+34937417700; pclave@csdm.cat

Omar Ortega, PhD

CONTACT

+34937417700; oortega@csdm.cat

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Double-blinded. Blinding will be applicable for clinical and instrumental assessments for investigators, and for intervention condition for patients.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Research and Academic Development at CSdM

Model Details: Single-center, double-blinded, two-arm, double-randomization RCT to assess the effect of paired sensory (capsaicin vs placebo) and motor stimulation (rTMS vs tDCS) for post-stroke patients with oropharyngeal dysphagia.

Study Record Dates

• First Submitted: January 17, 2023
• First Posted: February 9, 2023
• Study Start: November 28, 2022
• Primary Completion: December 1, 2024
• Study Completion: September 1, 2025
• Last Updated: February 13, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)