Clinical trial NCT04741620: Subacute Effect of Pharyngeal Pharmacological Sensory Stimulation in Elderly Patients With Oropharyngeal Dysphagia
Official title: Subacute Effect of Pharmacological Sensory Stimulation of the Oropharynx by Agonists of TRP Receptors in Swallowing Neurophysiology in the Elderly With Oropharyngeal Dysphagia.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Oropharyngeal Dysphagia
Dysphagia
Swallowing Disorder
Keywords: Oropharyngeal dysphagia
TRP agonists
Pharmacological stimulation
Sensory stimulation
Elderly
Lead sponsor: Hospital de Mataró
Sponsor class: OTHER
First posted: 2021-02-05
Enrollment: 150
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in the score of the Penetration Aspiration Scale
timeFrame: Baseline versus 2/3 days after the intervention
Secondary outcomes:
measure: Impaired safety of swallow
timeFrame: Baseline versus 2/3 days after the intervention
measure: Impaired efficacy
timeFrame: Baseline versus 2/3 days after the intervention
measure: Oropharyngeal swallow response (laryngeal vestibule closure time)
timeFrame: Baseline versus 2/3 days after the intervention
measure: Oropharyngeal swallow response (upper esophageal opening time)
timeFrame: Baseline versus 2/3 days after the intervention
measure: Oropharyngeal swallow response (laryngeal vestibule opening time)
timeFrame: Baseline versus 2/3 days after the intervention
measure: Oropharyngeal swallow response (Bolus final velocity)
timeFrame: Baseline versus 2/3 days after the intervention
measure: Pharyngeal sensory evoked potentials
timeFrame: Baseline versus 2/3 days after the intervention
measure: Pharyngeal motor evoked potentials
timeFrame: Baseline versus 2/3 days after the intervention
measure: Sensory threshold
timeFrame: Baseline versus 2/3 days after the intervention
measure: Substance P
timeFrame: Baseline versus 2/3 days after the intervention
measure: Palatability and comfort with the treatment.
timeFrame: Baseline versus 2/3 days after the intervention
Other outcomes:
Locations:
city: Mataró
country: Spain
facility: Consorci Sanitari del Maresme (Hospital de Mataró)
state: Barcelona
Study officials:
affiliation: Hospital de Mataró
name: Pere Clavé, PhD
role: PRINCIPAL_INVESTIGATOR
References: