Subacute Effect of Pharyngeal Pharmacological Sensory Stimulation in Elderly Patients With Oropharyngeal Dysphagia

NCT ID: NCT04741620

Last Updated: 2022-07-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

150 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-01-17

Study Completion Date

2022-03-27

Brief Summary

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Oropharyngeal sensory impairments are a potential target for treatment of oropharyngeal dysphagia (OD) in older patients. We previously found acute administration of TRP sensory stimulants improved VFS signs and swallow response. We hypothesized that sub-acute administration of TRP pharyngeal sensory stimulants, would improve cortical neuroplasticity and will lead into a faster and stronger swallow response, however desensitization of TRP receptors may occur. Therefore, the aim of the present study was to assess the biomechanical (Videofluoroscopy) and neurophysiological (pharyngeal sensory evoked potentials -PSEPs- and motor-evoked potentials (MEPs)) effect of 2 week treatment with TRP agonists in older patients with OD. Design: 150 older (\>70yr) patients with OD will be included in a Randomized Control Trial assessing the effect of oral administration of either: a) capsaicin (TRPV1); b) piperine (TRPV1/TRPA1) c) cinnamaldehyde (TRPA1); d) citric acid (ASIC3); e) capsaicin+citric acid (TRPV1/ASIC3); and f) placebo (Control). Measurements: 1) VFS signs of safety and efficacy of swallow and timing and extent of swallow response; 2) Latency, amplitude and cortical representation of PSEP and MEP; 3) Substance P concentration in saliva by ELISA as a marker of peripheral stimulation. Results from this study might help to develop new and effective pharmacological treatments for older dysphagic patients, from compensation to recovery of swallow function.

Detailed Description

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The project consists of a randomized, double-blind controlled interventional clinical trial (patient and analysis of results) with five treatment arms and a control group (placebo) involving a total of 150 elderly patients with oropharyngeal dysphagia (25 patients per group).

The recruitment of participants for the study will be carried out from the patients referred to the Dysphagia Unit of the Hospital de Mataró for the evaluation of swallowing disorders. The swallowing function of all candidates to be included in the study will be clinically evaluated using the volume-viscosity swallowing test (V-VST). Those patients with signs of impaired safety of swallowing during the examination (cough, decreased O2 saturation greater than 2% or voice change) will be candidates to participate in the study. They will be informed and in case of acceptance a saliva sample will be taken, and a videofluoroscopy (VFS) will be performed. If the patient presents impaired safety of swallow (Penetration aspiration scale higher or equal than 2), the patient will be definitively randomized to one of the branches of intervention and the rest of the explorations will proceed (sensory evoked potentials to pharyngeal electrical stimulation and pharyngeal motor evoked potentials to transcranial magnetic stimulation). After the treatment period a second evaluation of study procedures will be performed.

The treatment will consist of administering 10mL solution of the study product, according to randomization, 3 times a day (before breakfast, lunch and dinner) for 14 consecutive days after inclusion in the study. Treatment selected according our previous studies (Alvarez-Berdugo et al. Neurogastroenterol Motil 2017) are: Capsaicin 10microM, Piperine 150microM, Cinnamaldehyde 756,6microM + zinc 70microM, citric acid 457,5microM (pH=3,5), Capsaicin 10microM + citric acid 457,5microM (pH=3,5). For the control group, placebo product will be administered, which will be the vehicle solution with a more neutral pH.

Conditions

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Oropharyngeal Dysphagia Dysphagia Swallowing Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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Capsaicin 10microM

10mL capsaicin 10microM solution 3 times/day during 14 consecutive days (2 weeks).

Group Type ACTIVE_COMPARATOR

Piperine 150microM (TRPV1 & TRPA1 natural agonist)

Intervention Type OTHER

10 mL Piperine 150microM solution 3 times per day (before each meal) during 14 consecutive days.

Cinnamaldehyde 756,6microM + zinc 70microM (TRPA1 natural agonist)

Intervention Type OTHER

10 mL Cinnamaldehyde 756,6microM + zinc 70microM solution 3 times per day (before each meal) during 14 consecutive days.

Citric acid 457,5microM (pH=3,5) (ASIC3 natural agonist)

Intervention Type OTHER

10 mL Citric acid 457,5microM (pH=3,5) solution 3 times per day (before each meal) during 14 consecutive days.

Capsaicin 10microM + Citric acid 457,5microM (pH=3,5) (TRPV1 & ASIC3 natural agonists)

Intervention Type OTHER

10 mL Capsaicin 10microM + Citric acid 457,5microM (pH=3,5) solution 3 times per day (before each meal) during 14 consecutive days.

Placebo (Methyl benzoate, Propyl benzoate, Propylenglycol)

Intervention Type OTHER

10 mL placebo solution 3 times per day (before each meal) during 14 consecutive days.

Piperine 150microM

10mL Piperine 150microM solution 3 times/day during 14 consecutive days (2 weeks).

Group Type ACTIVE_COMPARATOR

Capsaicin 10microM (TRPV1 natural agonist)

Intervention Type OTHER

10 mL Capsaicin 10microM solution 3 times per day (before each meal) during 14 consecutive days.

Cinnamaldehyde 756,6microM + zinc 70microM (TRPA1 natural agonist)

Intervention Type OTHER

10 mL Cinnamaldehyde 756,6microM + zinc 70microM solution 3 times per day (before each meal) during 14 consecutive days.

Citric acid 457,5microM (pH=3,5) (ASIC3 natural agonist)

Intervention Type OTHER

10 mL Citric acid 457,5microM (pH=3,5) solution 3 times per day (before each meal) during 14 consecutive days.

Capsaicin 10microM + Citric acid 457,5microM (pH=3,5) (TRPV1 & ASIC3 natural agonists)

Intervention Type OTHER

10 mL Capsaicin 10microM + Citric acid 457,5microM (pH=3,5) solution 3 times per day (before each meal) during 14 consecutive days.

Placebo (Methyl benzoate, Propyl benzoate, Propylenglycol)

Intervention Type OTHER

10 mL placebo solution 3 times per day (before each meal) during 14 consecutive days.

Cinnamaldehyde 756,6microM + zinc 70microM

10mL Cinnamaldehyde 756,6microM + zinc 70microM solution 3 times/day during 14 consecutive days (2 weeks).3 times/day during 14 consecutive days (2 weeks).

Group Type ACTIVE_COMPARATOR

Capsaicin 10microM (TRPV1 natural agonist)

Intervention Type OTHER

10 mL Capsaicin 10microM solution 3 times per day (before each meal) during 14 consecutive days.

Piperine 150microM (TRPV1 & TRPA1 natural agonist)

Intervention Type OTHER

10 mL Piperine 150microM solution 3 times per day (before each meal) during 14 consecutive days.

Citric acid 457,5microM (pH=3,5) (ASIC3 natural agonist)

Intervention Type OTHER

10 mL Citric acid 457,5microM (pH=3,5) solution 3 times per day (before each meal) during 14 consecutive days.

Capsaicin 10microM + Citric acid 457,5microM (pH=3,5) (TRPV1 & ASIC3 natural agonists)

Intervention Type OTHER

10 mL Capsaicin 10microM + Citric acid 457,5microM (pH=3,5) solution 3 times per day (before each meal) during 14 consecutive days.

Placebo (Methyl benzoate, Propyl benzoate, Propylenglycol)

Intervention Type OTHER

10 mL placebo solution 3 times per day (before each meal) during 14 consecutive days.

Citric acid 457,5microM (pH=3,5)

10mL Citric acid 457,5microM (pH=3,5) solution 3 times/day during 14 consecutive days (2 weeks).3 times/day during 14 consecutive days (2 weeks).

Group Type ACTIVE_COMPARATOR

Capsaicin 10microM (TRPV1 natural agonist)

Intervention Type OTHER

10 mL Capsaicin 10microM solution 3 times per day (before each meal) during 14 consecutive days.

Piperine 150microM (TRPV1 & TRPA1 natural agonist)

Intervention Type OTHER

10 mL Piperine 150microM solution 3 times per day (before each meal) during 14 consecutive days.

Cinnamaldehyde 756,6microM + zinc 70microM (TRPA1 natural agonist)

Intervention Type OTHER

10 mL Cinnamaldehyde 756,6microM + zinc 70microM solution 3 times per day (before each meal) during 14 consecutive days.

Capsaicin 10microM + Citric acid 457,5microM (pH=3,5) (TRPV1 & ASIC3 natural agonists)

Intervention Type OTHER

10 mL Capsaicin 10microM + Citric acid 457,5microM (pH=3,5) solution 3 times per day (before each meal) during 14 consecutive days.

Placebo (Methyl benzoate, Propyl benzoate, Propylenglycol)

Intervention Type OTHER

10 mL placebo solution 3 times per day (before each meal) during 14 consecutive days.

Capsaicin 10microM + Citric acid 457,5microM (pH=3,5)

10mL Capsaicin 10microM + Citric acid 457,5microM (pH=3,5) solution 3 times/day during 14 consecutive days (2 weeks).3 times/day during 14 consecutive days (2 weeks).

Group Type ACTIVE_COMPARATOR

Capsaicin 10microM (TRPV1 natural agonist)

Intervention Type OTHER

10 mL Capsaicin 10microM solution 3 times per day (before each meal) during 14 consecutive days.

Piperine 150microM (TRPV1 & TRPA1 natural agonist)

Intervention Type OTHER

10 mL Piperine 150microM solution 3 times per day (before each meal) during 14 consecutive days.

Cinnamaldehyde 756,6microM + zinc 70microM (TRPA1 natural agonist)

Intervention Type OTHER

10 mL Cinnamaldehyde 756,6microM + zinc 70microM solution 3 times per day (before each meal) during 14 consecutive days.

Citric acid 457,5microM (pH=3,5) (ASIC3 natural agonist)

Intervention Type OTHER

10 mL Citric acid 457,5microM (pH=3,5) solution 3 times per day (before each meal) during 14 consecutive days.

Placebo (Methyl benzoate, Propyl benzoate, Propylenglycol)

Intervention Type OTHER

10 mL placebo solution 3 times per day (before each meal) during 14 consecutive days.

Placebo

10mL placebo solution 3 times/day during 14 consecutive days (2 weeks).3 times/day during 14 consecutive days (2 weeks).

Group Type PLACEBO_COMPARATOR

Capsaicin 10microM (TRPV1 natural agonist)

Intervention Type OTHER

10 mL Capsaicin 10microM solution 3 times per day (before each meal) during 14 consecutive days.

Piperine 150microM (TRPV1 & TRPA1 natural agonist)

Intervention Type OTHER

10 mL Piperine 150microM solution 3 times per day (before each meal) during 14 consecutive days.

Cinnamaldehyde 756,6microM + zinc 70microM (TRPA1 natural agonist)

Intervention Type OTHER

10 mL Cinnamaldehyde 756,6microM + zinc 70microM solution 3 times per day (before each meal) during 14 consecutive days.

Citric acid 457,5microM (pH=3,5) (ASIC3 natural agonist)

Intervention Type OTHER

10 mL Citric acid 457,5microM (pH=3,5) solution 3 times per day (before each meal) during 14 consecutive days.

Capsaicin 10microM + Citric acid 457,5microM (pH=3,5) (TRPV1 & ASIC3 natural agonists)

Intervention Type OTHER

10 mL Capsaicin 10microM + Citric acid 457,5microM (pH=3,5) solution 3 times per day (before each meal) during 14 consecutive days.

Interventions

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Capsaicin 10microM (TRPV1 natural agonist)

10 mL Capsaicin 10microM solution 3 times per day (before each meal) during 14 consecutive days.

Intervention Type OTHER

Piperine 150microM (TRPV1 & TRPA1 natural agonist)

10 mL Piperine 150microM solution 3 times per day (before each meal) during 14 consecutive days.

Intervention Type OTHER

Cinnamaldehyde 756,6microM + zinc 70microM (TRPA1 natural agonist)

10 mL Cinnamaldehyde 756,6microM + zinc 70microM solution 3 times per day (before each meal) during 14 consecutive days.

Intervention Type OTHER

Citric acid 457,5microM (pH=3,5) (ASIC3 natural agonist)

10 mL Citric acid 457,5microM (pH=3,5) solution 3 times per day (before each meal) during 14 consecutive days.

Intervention Type OTHER

Capsaicin 10microM + Citric acid 457,5microM (pH=3,5) (TRPV1 & ASIC3 natural agonists)

10 mL Capsaicin 10microM + Citric acid 457,5microM (pH=3,5) solution 3 times per day (before each meal) during 14 consecutive days.

Intervention Type OTHER

Placebo (Methyl benzoate, Propyl benzoate, Propylenglycol)

10 mL placebo solution 3 times per day (before each meal) during 14 consecutive days.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* More than 70 years old.
* Oropharyngeal dysphagia with impaired safety of swallow (penetration aspiration score higher or equal than 2).
* Patients able to comply with the study protocol.
* Signature or the written informed consent.

Exclusion Criteria

* Previous history of severe gastrointestinal diseases.
* Epilepsy or previous convulsive crisis episodes.
* Pacemaker or implanted defibrillator carriers.
* Cardiopulmonary instability.
* Oropharyngeal dysphagia of structural cause.
* Previous history of head and neck surgery.
* Neurodegenerative disease.
* Advanced dementia (GDS higher than 5).
* Gastroesophageal reflux.
* Taking drugs with effects on dopamine.
* Neoplasia or active infection.
* Alcohol, tobacco or drugs dependence.
* Participate or have participated in another interventionist clinical trial in the 4 weeks prior to inclusion.
Minimum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hospital de Mataró

OTHER

Sponsor Role lead

Responsible Party

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Pere Clave

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Pere Clavé, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital de Mataró

Locations

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Consorci Sanitari del Maresme (Hospital de Mataró)

Mataró, Barcelona, Spain

Site Status

Countries

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Spain

References

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Guanyabens N, Tomsen N, Palomeras E, Mundet L, Clave P, Ortega O. Neurophysiological characterization of oropharyngeal dysphagia in older patients. Clin Neurophysiol. 2024 Jun;162:129-140. doi: 10.1016/j.clinph.2024.03.030. Epub 2024 Apr 4.

Reference Type DERIVED
PMID: 38615499 (View on PubMed)

Other Identifiers

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PI18/00241

Identifier Type: -

Identifier Source: org_study_id

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