Clinical trial NCT05735626: Treatment of Acute Post-stroke Oropharyngeal Dysphagia With Paired Stimulation
Official title: Treatment of Acute Post-stroke Oropharyngeal Dysphagia With Paired Stimulation Through Peripheral TRVP1 Agonists and Non-invasive Brain Stimulation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Stroke
Stroke, Acute
Oropharyngeal Dysphagia
Swallowing Disorder
Keywords: TRPV1 agonists
TRPV1/A1 agonists
Transcranial Direct Current Stimulation
Non-invasive Brain Stimulation
Sensory Stimulation
Capsaicin
Lead sponsor: Hospital de Mataró
Sponsor class: OTHER
Collaborators: name: Consorci Sanitari del Maresme
name: Instituto de Salud Carlos III
First posted: 2023-02-21
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 2 days randomized crossover study with 60 patients in 3 treatment groups:

* Piperine 150μM + tDCS 2mA 20'
* Piperine 1mM+ tDCS 2mA 20'
* Capsaicin 10μM + tDCS 2mA 20
Primary purpose: TREATMENT

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 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Changes in swallowing function
timeFrame: Day 1, +24 hours, and at 3 months follow-up.
measure: Changes in spontaneous swallowing frequency
timeFrame: Day 1, +24 hours, and at 3 months follow-up.
Secondary outcomes:
measure: Nutritional status (MNA-sf)
timeFrame: Baseline and 3 months follow-up visits.
measure: Anthropometrics
timeFrame: Baseline and 3 months follow-up visits.
measure: Bioimpedance
timeFrame: Day 1, +24 hours, and at 3 months follow-up.
measure: Blood analysis
timeFrame: Baseline and 3 months follow-up visits.
measure: Neuropeptides in saliva determination
timeFrame: Day 1, +24 hours, and at 3 months follow-up.
measure: Length of hospital stay
timeFrame: From baseline to the end of the study (3-months follow-up visit).
measure: Aspiration pneumonia admissions
timeFrame: From baseline to the end of the study (3-months follow-up visit).
measure: General hospital readmissions
timeFrame: From baseline to the end of the study (3-months follow-up visit).
measure: Mortality over the study period
timeFrame: From baseline to the end of the study (3-months follow-up visit).
measure: Safety of the treatment
timeFrame: From baseline to the end of the study (3-months follow-up visit).
Other outcomes:
Locations:
city: Mataró
country: Spain
facility: Hospital de Mataró. Consorci Sanitari del Mareme.
state: Barcelona
Study officials:
affiliation: Consorci Sanitari del Maresme
name: Pere Clavé, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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 Y Acad Sci. 2016 Sep;1380(1):121-138. doi: 10.1111/nyas.13135. Epub 2016 Jul 11.
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.
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 Sci. 2022 Sep 15;23(18):10773. doi: 10.3390/ijms231810773.
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. Epub 2019 Apr 5.
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.
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 Proof-of-Concept Study. Diagnostics (Basel). 2021 Mar 7;11(3):461. doi: 10.3390/diagnostics11030461.
citation: 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/s00455-022-10451-3. Epub 2022 Apr 23.