Treatment of Acute Post-stroke Oropharyngeal Dysphagia With Paired Stimulation

Stroke Clinical Trial

— ICI20/00117  

Official title:

Treatment of Acute Post-stroke Oropharyngeal Dysphagia With Paired Stimulation Through Peripheral TRVP1 Agonists and Non-invasive Brain Stimulation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05735626
• Other study ID #: STROD_ICI_A
• Status: Recruiting
• Phase: N/A
• Start date: July 1, 2021
• Est. completion date: April 2024

Study information

• Verified date: February 2023
• Source: Hospital de Mataró
• Contact: Pere Clavé, MD, PhD
• Phone: +34937417700
• Email: pclave[@]csdm.cat
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 or piperine and of central motor noninvasive brain stimulation techniques such as transcranial direct current stimulation (tDCS) will be studied. Pairing sensory peripheral and central stimulation may produce greater benefits. The main aim of the project is to study the efficacy of a novel protocol of paired stimulation on acute PS-OD patients. The investigators will assess the acute application of tDCS/piperine or tDCS/capsaicin in the acute phase of stroke, will improve PS-OD. 2 days randomized crossover study with 60 patients in 3 treatment groups (60 patients in the acute stroke phase divided in 3 study arms). We will assess changes in swallow safety, and neurophysiology of the swallow, hospital stay, respiratory and nutritional complications, mortality and QoL.

Description:

• Main hypothesis: Paired neurorehabilitation treatment targeting both pharyngeal sensory and motor components simultaneously through a peripheral pharmacological stimulant (transient receptor potential cation channel [TRPV1] agonist, capsaicin) and central stimulation (NIBS) (tDCS) can improve swallowing function in acute PS-OD patients by promoting cortical plasticity, their QoL and reduce OD associated complications.

• Main objectives: to study the efficacy of a novel protocol of paired stimulation on acute PS-OD patients. The investigators will assess the acute application of tDCS/piperine or tDCS/capsaicin in the acute phase of stroke.

• Secondary aims: to assess 1) safety and adverse events; 2) the effects on safety of swallow with a standardized protocol of swallowing evaluation; 3) clinical outcomes at 3 months follow up; 4) the effect of the treatments on spontaneous swallowing frequency and responsiveness to treatment according to stroke characteristics; 5) the effect in the acute phase on functional severity of OD and specific clinical outcomes.

• Design: 2 days randomized crossover study with 60 patients in 3 treatment groups (60 patients in the acute stroke phase divided in 3 study arms). We will assess changes in swallow safety, and neurophysiology of the swallow, hospital stay, respiratory and nutritional complications, mortality and QoL.

• Study population: 60 Acute PS-OD hospitalized patients.

• Inclusion criteria: Adult patients consecutively admitted with recent (<1month) unilateral hemispheric stroke; impaired safety of swallow (ISS) (V-VST); conscious (NIHSS quest. 1a=0); able to follow the protocol and to give written informed consent (WIC).

• Exclusion criteria: Pregnancy; life expectancy <3m or palliative care; neurodegenerative disorder or previous OD; implanted electronic device; epilepsy; metal in the head; participation in another clinical trial in the previous month.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: April 2024
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Unilateral acute stroke (up to 15 days of evolution).

• Impaired safety or efficacy of swallow according the volume-viscosity swallowing test (V-VST).

• Conscious patient (NIHSS 1a = 0).

• Patient able to follow the protocol and give written informed consent or, failing that, by a family member or legal representative.

Exclusion Criteria:

• Pregnancy.

• Life expectancy less than 3m or palliative care.

• Neurodegenerative disorder.

• Comprehension aphasia.

• Dementia (GDS 4 or higher).

• Previously diagnosed oropharyngeal dysphagia (dysphagia not related to stroke).

• Implanted electronic device.

• Epilepsy.

• Metal in the head.

• Patients with suspected or PCR-confirmed SARS-CoV-2 infection

• Participation in another clinical trial in the previous month.

Related Conditions & MeSH terms

• Deglutition Disorders
• Oropharyngeal Dysphagia
• Stroke
• Stroke, Acute
• Swallowing Disorder

Intervention

Combination Product:
• Piperine 150µM + tDCS 2mA
2 days treatment with either sham + placebo or piperine 150µM + tDCS 2mA (cross-over randomized study).
• Piperine 1mM + tDCS 2mA
2 days treatment with either sham + placebo or piperine 1mM + tDCS 2mA (cross-over randomized study).
• Capsaicin 10µM + tDCS 2mA
2 days treatment with either sham + placebo or capsaicin 10µM + tDCS 2mA (cross-over randomized study).

Locations

Country	Name	City	State
Spain	Hospital de Mataró. Consorci Sanitari del Mareme.	Mataró	Barcelona

Sponsors (3)

Lead Sponsor	Collaborator
Hospital de Mataró	Consorci Sanitari del Maresme, Instituto de Salud Carlos III

Country where clinical trial is conducted

Spain, 

References & Publications (8)

Alvarez-Larruy M, Tomsen N, Guanyabens N, Palomeras E, Clave P, Nascimento W. Spontaneous Swallowing Frequency in Post-Stroke Patients with and Without Oropharyngeal Dysphagia: An Observational Study. Dysphagia. 2023 Feb;38(1):200-210. doi: 10.1007/s00455 — View Citation

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 — View Citation

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. — View Citation

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. — View Citation

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 Proo — View Citation

Rofes L, Arreola V, Martin A, Clave P. Effect of oral piperine on the swallow response of patients with oropharyngeal dysphagia. J Gastroenterol. 2014 Dec;49(12):1517-23. doi: 10.1007/s00535-013-0920-0. Epub 2013 Dec 11. — View Citation

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 Sc — View Citation

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in swallowing function	Changes in the volume-viscosity swallowing test to assess prevalence of signs of impaired efficacy and safety of swallow. Evaluated at visit baseline, post-treatment and at 3 months follow-up).	Day 1, +24 hours, and at 3 months follow-up.
Primary	Changes in spontaneous swallowing frequency	Changes in the electromyographical evaluation of spontaneous swallowing frequency obtaining the number of swallows/min, the amplitude and the latency of swallows. 5 times pre-post treatment visits 1 and pre-post treatment visit 2 and 1 time at 3 months follow-up.	Day 1, +24 hours, and at 3 months follow-up.
Secondary	Nutritional status (MNA-sf)	Mini nutritional assessment short form score (nutritional status questionnaire).	Baseline and 3 months follow-up visits.
Secondary	Anthropometrics	Weight, height and body mass index.	Baseline and 3 months follow-up visits.
Secondary	Bioimpedance	Bioimpedance parameters (total body water, extracellular water, intracellular water, phase angle, muscle mass and cell mass)	Day 1, +24 hours, and at 3 months follow-up.
Secondary	Blood analysis	Analytical parameters (albumin, pre-albumin, total protein, total lymphocytes and total cholesterol).	Baseline and 3 months follow-up visits.
Secondary	Neuropeptides in saliva determination	Determination by ELISA of concentration of the neuropeptides substance P and CGRP (Calcitonin gene-related peptide) in saliva sample.	Day 1, +24 hours, and at 3 months follow-up.
Secondary	Length of hospital stay	length of stay during the study.	From baseline to the end of the study (3-months follow-up visit).
Secondary	Aspiration pneumonia admissions	Aspiration pneumonia admissions during the study period.	From baseline to the end of the study (3-months follow-up visit).
Secondary	General hospital readmissions	General hospital readmissions by any cause during the study period.	From baseline to the end of the study (3-months follow-up visit).
Secondary	Mortality over the study period	Mortality over the study period.	From baseline to the end of the study (3-months follow-up visit).
Secondary	Safety of the treatment	Safety of the treatment applied (adverse events rate) during all the study period.	From baseline to the end of the study (3-months follow-up visit).