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Treatment of Acute Post-stroke Oropharyngeal Dysphagia With Paired Stimulation

Not Applicable
Recruiting
Conditions
Swallowing Disorder
Stroke
Stroke, Acute
Oropharyngeal Dysphagia
Interventions
Combination Product: Piperine 1mM + tDCS 2mA
Combination Product: Capsaicin 10μM + tDCS 2mA
Combination Product: Piperine 150μM + tDCS 2mA
Registration Number
NCT05735626
Lead Sponsor
Hospital de Mataró
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
60
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Piperine 1mM+ tDCS 2mAPiperine 1mM + tDCS 2mAtDCS 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.
Capsaicin 10μM + tDCS 2mACapsaicin 10μM + tDCS 2mAtDCS 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.
Piperine 150μM + tDCS 2mAPiperine 150μM + tDCS 2mAtDCS 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.
Primary Outcome Measures
NameTimeMethod
Changes in spontaneous swallowing frequencyDay 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.

Changes in swallowing functionDay 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).

Secondary Outcome Measures
NameTimeMethod
AnthropometricsBaseline and 3 months follow-up visits.

Weight, height and body mass index.

BioimpedanceDay 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 analysisBaseline and 3 months follow-up visits.

Analytical parameters (albumin, pre-albumin, total protein, total lymphocytes and total cholesterol).

Nutritional status (MNA-sf)Baseline and 3 months follow-up visits.

Mini nutritional assessment short form score (nutritional status questionnaire).

Neuropeptides in saliva determinationDay 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.

Aspiration pneumonia admissionsFrom baseline to the end of the study (3-months follow-up visit).

Aspiration pneumonia admissions during the study period.

General hospital readmissionsFrom 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 periodFrom baseline to the end of the study (3-months follow-up visit).

Mortality over the study period.

Length of hospital stayFrom baseline to the end of the study (3-months follow-up visit).

length of stay during the study.

Safety of the treatmentFrom 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.

Trial Locations

Locations (1)

Hospital de Mataró. Consorci Sanitari del Mareme.

🇪🇸

Mataró, Barcelona, Spain

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