ICI20/00117: Treatment of Acute Post-stroke Oropharyngeal Dysphagia With Paired Stimulation

Sponsor

Hospital de Mataró (Other)

Overall Status

Recruiting

CT.gov ID

NCT05735626

Collaborator

Consorci Sanitari del Maresme (Other), Instituto de Salud Carlos III (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Stroke Stroke, Acute Oropharyngeal Dysphagia Swallowing Disorder	Combination Product: Piperine 150μM + tDCS 2mA Combination Product: Piperine 1mM + tDCS 2mA Combination Product: Capsaicin 10μM + tDCS 2mA	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

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 202 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

Masking:

Triple (Participant, Care Provider, Outcomes Assessor)

Masking Description:

Blinding will be applicable for clinical and instrumental assessments for investigators, and for intervention condition for patients.

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 1, 2021

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Apr 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Piperine 150μM + tDCS 2mA tDCS will be applied for 20 minutes at 2.0 mA (NeuroConn, Germany) with the anode electrode positioned over the pharyngeal primary motor cortex (M1) of the unaffected hemisphere (3.5 cm lateral / 1 cm anterior to the vertex) and the cathode over the opposite supraorbital region. During central stimulation, 5 ml of piperine (150μM) will be administered orally every 5 min. After each administration, the patient will be asked to perform dry swallows every minute. In order to avoid alterations in the safety and efficacy of swallowing during the procedure, the bolus will be rheologically adapted according to the patient's requirements. Crossover study, each arm includes a placebo + sham stimulation in one of the two days of treatment. Patients will initiate either placebo + sham stimulation or piperine + tDCS randomly in the first or second day depending on the randomization.	Combination Product: Piperine 150μM + tDCS 2mA 2 days treatment with either sham + placebo or piperine 150μM + tDCS 2mA (cross-over randomized study).
Experimental: Piperine 1mM+ tDCS 2mA tDCS will be applied for 20 minutes at 2.0 mA with the anode electrode positioned over the pharyngeal primary motor cortex (M1) of the unaffected hemisphere (3.5 cm lateral / 1 cm anterior to the vertex) and the cathode over the opposite supraorbital region. During central stimulation, 5 ml of piperine (1 mM) will be administered orally every 5 min. After each administration, the patient will be asked to perform dry swallows every minute. In order to avoid alterations in the safety and efficacy of swallowing during the procedure, the bolus will be rheologically adapted according to the patient's requirements. Crossover study, each arm includes a placebo + sham stimulation in one of the two days of treatment. Patients will initiate either placebo + sham stimulation or piperine + tDCS randomly in the first or second day depending on the randomization.	Combination Product: Piperine 1mM + tDCS 2mA 2 days treatment with either sham + placebo or piperine 1mM + tDCS 2mA (cross-over randomized study).
Experimental: Capsaicin 10μM + tDCS 2mA tDCS will be applied for 20 minutes at 2.0 mA with the anode electrode positioned over the pharyngeal primary motor cortex (M1) of the unaffected hemisphere (3.5 cm lateral / 1 cm anterior to the vertex) and the cathode over the opposite supraorbital region. During central stimulation, 5 ml of capsaicin (10 μM) will be administered orally every 5 min. After each administration, the patient will be asked to perform dry swallows every minute. In order to avoid alterations in the safety and efficacy of swallowing during the procedure, the bolus will be rheologically adapted according to the patient's requirements. Crossover study, each arm includes a placebo + sham stimulation in one of the two days of treatment. Patients will initiate either placebo + sham stimulation or capsaicin + tDCS randomly in the first or second day depending on the randomization.	Combination Product: Capsaicin 10μM + tDCS 2mA 2 days treatment with either sham + placebo or capsaicin 10μM + tDCS 2mA (cross-over randomized study).

Arm

Intervention/Treatment

Experimental: Piperine 150μM + tDCS 2mA

tDCS will be applied for 20 minutes at 2.0 mA (NeuroConn, Germany) with the anode electrode positioned over the pharyngeal primary motor cortex (M1) of the unaffected hemisphere (3.5 cm lateral / 1 cm anterior to the vertex) and the cathode over the opposite supraorbital region. During central stimulation, 5 ml of piperine (150μM) will be administered orally every 5 min. After each administration, the patient will be asked to perform dry swallows every minute. In order to avoid alterations in the safety and efficacy of swallowing during the procedure, the bolus will be rheologically adapted according to the patient's requirements. Crossover study, each arm includes a placebo + sham stimulation in one of the two days of treatment. Patients will initiate either placebo + sham stimulation or piperine + tDCS randomly in the first or second day depending on the randomization.

Combination Product: Piperine 150μM + tDCS 2mA

2 days treatment with either sham + placebo or piperine 150μM + tDCS 2mA (cross-over randomized study).

Experimental: Piperine 1mM+ tDCS 2mA

tDCS will be applied for 20 minutes at 2.0 mA with the anode electrode positioned over the pharyngeal primary motor cortex (M1) of the unaffected hemisphere (3.5 cm lateral / 1 cm anterior to the vertex) and the cathode over the opposite supraorbital region. During central stimulation, 5 ml of piperine (1 mM) will be administered orally every 5 min. After each administration, the patient will be asked to perform dry swallows every minute. In order to avoid alterations in the safety and efficacy of swallowing during the procedure, the bolus will be rheologically adapted according to the patient's requirements. Crossover study, each arm includes a placebo + sham stimulation in one of the two days of treatment. Patients will initiate either placebo + sham stimulation or piperine + tDCS randomly in the first or second day depending on the randomization.

Combination Product: Piperine 1mM + tDCS 2mA

2 days treatment with either sham + placebo or piperine 1mM + tDCS 2mA (cross-over randomized study).

Experimental: Capsaicin 10μM + tDCS 2mA

tDCS will be applied for 20 minutes at 2.0 mA with the anode electrode positioned over the pharyngeal primary motor cortex (M1) of the unaffected hemisphere (3.5 cm lateral / 1 cm anterior to the vertex) and the cathode over the opposite supraorbital region. During central stimulation, 5 ml of capsaicin (10 μM) will be administered orally every 5 min. After each administration, the patient will be asked to perform dry swallows every minute. In order to avoid alterations in the safety and efficacy of swallowing during the procedure, the bolus will be rheologically adapted according to the patient's requirements. Crossover study, each arm includes a placebo + sham stimulation in one of the two days of treatment. Patients will initiate either placebo + sham stimulation or capsaicin + tDCS randomly in the first or second day depending on the randomization.

Combination Product: Capsaicin 10μM + tDCS 2mA

2 days treatment with either sham + placebo or capsaicin 10μM + tDCS 2mA (cross-over randomized study).

Outcome Measures

Primary Outcome Measures

Changes in swallowing function [Day 1, +24 hours, and at 3 months follow-up.]
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).
Changes in spontaneous swallowing frequency [Day 1, +24 hours, and at 3 months follow-up.]
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.

Secondary Outcome Measures

Nutritional status (MNA-sf) [Baseline and 3 months follow-up visits.]
Mini nutritional assessment short form score (nutritional status questionnaire).
Anthropometrics [Baseline and 3 months follow-up visits.]
Weight, height and body mass index.
Bioimpedance [Day 1, +24 hours, and at 3 months follow-up.]
Bioimpedance parameters (total body water, extracellular water, intracellular water, phase angle, muscle mass and cell mass)
Blood analysis [Baseline and 3 months follow-up visits.]
Analytical parameters (albumin, pre-albumin, total protein, total lymphocytes and total cholesterol).
Neuropeptides in saliva determination [Day 1, +24 hours, and at 3 months follow-up.]
Determination by ELISA of concentration of the neuropeptides substance P and CGRP (Calcitonin gene-related peptide) in saliva sample.
Length of hospital stay [From baseline to the end of the study (3-months follow-up visit).]
length of stay during the study.
Aspiration pneumonia admissions [From baseline to the end of the study (3-months follow-up visit).]
Aspiration pneumonia admissions during the study period.
General hospital readmissions [From baseline to the end of the study (3-months follow-up visit).]
General hospital readmissions by any cause during the study period.
Mortality over the study period [From baseline to the end of the study (3-months follow-up visit).]
Mortality over the study period.
Safety of the treatment [From baseline to the end of the study (3-months follow-up visit).]
Safety of the treatment applied (adverse events rate) during all the study period.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.