Treatment of Acute Post-stroke Oropharyngeal Dysphagia With Paired Stimulation

NCT05735626 | Unknown

• 1 other identifier: STROD_ICI_A
• Study Type: interventional
• Target: 60
• 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 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.

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

Outcome Measures

Primary Outcomes (2)

• 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.

• 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 Outcomes (10)

• Nutritional status (MNA-sf)

  Baseline and 3 months follow-up visits.

• Anthropometrics

  Baseline and 3 months follow-up visits.

• Bioimpedance

  Day 1, +24 hours, and at 3 months follow-up.

• Blood analysis

  Baseline and 3 months follow-up visits.

• Neuropeptides in saliva determination

  Day 1, +24 hours, and at 3 months follow-up.

Study Arms (3)

Piperine 150μM + tDCS 2mA

EXPERIMENTAL

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

Piperine 1mM+ tDCS 2mA

EXPERIMENTAL

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

Capsaicin 10μM + tDCS 2mA

EXPERIMENTAL

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

Interventions

Piperine 150μM + tDCS 2mA COMBINATION_PRODUCT

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

Piperine 150μM + tDCS 2mA

Piperine 1mM + tDCS 2mA COMBINATION_PRODUCT

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

Piperine 1mM+ tDCS 2mA

Capsaicin 10μM + tDCS 2mA COMBINATION_PRODUCT

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

Capsaicin 10μM + tDCS 2mA

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

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 (8)

• 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

• 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

• 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

• 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

• 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

• 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.

  PMID: 24326980 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

• 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.

  PMID: 35460440 RESULT

MeSH Terms

Conditions

Stroke; Deglutition Disorders

Interventions

piperine; Capsaicin

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Pharyngeal Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Polyunsaturated Alkamides; Amides; Organic Chemicals; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Fatty Acids; Lipids

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: Blinding will be applicable for clinical and instrumental assessments for investigators, and for intervention condition for patients.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Research and Academic Development at CSdM

Model Details: 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

Study Record Dates

• First Submitted: January 17, 2023
• First Posted: February 21, 2023
• Study Start: July 1, 2021
• Primary Completion: December 1, 2023
• Study Completion: April 1, 2024
• Last Updated: February 21, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)