Effects of 6-month of Treatment With TRPV1 and TRPA1 Agonists in Older Patients With OD

Biomechanical, Neurophysiological and Clinical Effects of 6-month Stimulation Using TRPV1 and TRPA1 Agonists in Older Patients With Oropharyngeal Dysphagia

In recent years, the investigators have characterized the impairments in pharyngeal sensory function associated with swallowing disorders in older patients with oropharyngeal dysphagia (OD). The investigators have demonstrated the acute and sub-acute therapeutic effect of TRP agonists on mechanical and neural swallow responses in patients with OD. The present hypothesis is that 6-months treatment with TRPV1 (capsaicin) or TRPA1 (piperine) agonists will improve the biomechanics and neurophysiology of the swallow response without inducing desensitization. The aim of this study is to evaluate the effect on biomechanics assessed by videofluoroscopy (VFS), neurophysiology (pharyngeal evoked sensory potentials -pSEP- and motor evoked potentials -pMEP-), and clinical outcomes during a 6-month treatment with TRP agonists added to the alimentary bolus 3 times a day in older patients with OD. Design: 150 older patients (>70y) with OD will be included in a randomized clinical trial with three treatment arms, in which the effect of oral administration of 1) capsaicin 10µM (TRPV1 agonist), 2) piperine 150µM (TRPA1), and 3) placebo (Control), will be evaluated. Measurements: 1) VFS signs of swallowing safety and efficacy and timing of swallow response ; 2) Spontaneous swallowing frequency; 3) Latency, amplitude and cortical representation of pSEP and pMEP; 4) Concentration of substance P and CGRP in saliva, 5) Clinical outcomes (respiratory and nutritional complications). The results of this study will increase evidence for a new generation of pharmacological treatments for older patients with OD, moving from compensation to rehabilitation of the swallowing function.

Study Overview

• Status: Not yet recruiting
• Conditions: Oropharyngeal Dysphagia; Swallowing Disorder
• Intervention / Treatment: Dietary supplement: Capsaicin; Dietary supplement: Piperine; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pere Clavé, PhD; Phone Number: 2284 937417700; Email: pere.clave@ciberehd.org

Study Locations

• Spain
  • Barcelona
    • Mataró, Barcelona, Spain, 08304
      • Hospital de Mataro

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥70 years
• With a positive Volume-Viscosity Swallow Test for oropharyngeal dysphagia
• Penetration-aspiration scale >1 in videofluoroscopy
• Able to follow the protocol and to give written informed consent.

Exclusion Criteria:

• Life expectancy < 3m or palliative care
• Allergy to iodinated contrast or to the components of the treatment solutions
• Cancer or active infection
• Implanted electronic device
• Epilepsy
• Metal in the head
• Participation in another clinical trial (previous month).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Capsaicin; Natural TRPV1 agonist at a concentration of 10mcM. Posology: 10 mL every 8h for 6 month.	Dietary supplement: Capsaicin; Oral stimulation with natural TRPV1 agonist
Active Comparator: Piperine; Natural TRPA1/V1 agonist at a concentration of 150mcM. Posology: 10 mL every 8h for 6 month.	Dietary supplement: Piperine; Oral stimulation with natural TRPA1/V1 agonist
Placebo Comparator: Placebo; Deionized water + the same preservatives as in the active treatments	Dietary supplement: Placebo; Oral stimulation with placebo solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of oropharyngeal dysphagia	The severity of oropharyngeal dysphagia will be determined according the penetration-aspiration scale during the videofluoroscopy: Material does not enter the airway.; Material enters the airway. Remains above vocal cords and is ejected from the airway.; Material is above vocal cords and is not ejected from the airway.; Material enters the airway, contacts vocal cords and is ejected from the airway.; Material contacts the vocal cords and is not ejected from the airway.; Material passes below the vocal cords and is ejected into larynx or out of the airway.; Material passes below the vocal cords and is not ejected from the trachea despite effort.; Material enters the airway, passes below the vocal cords and no effort is made to eject the material	Pre treatment visit
Severity of oropharyngeal dysphagia	The severity of oropharyngeal dysphagia will be determined according the penetration-aspiration scale during the videofluoroscopy: Material does not enter the airway.; Material enters the airway. Remains above vocal cords and is ejected from the airway.; Material is above vocal cords and is not ejected from the airway.; Material enters the airway, contacts vocal cords and is ejected from the airway.; Material contacts the vocal cords and is not ejected from the airway.; Material passes below the vocal cords and is ejected into larynx or out of the airway.; Material passes below the vocal cords and is not ejected from the trachea despite effort.; Material enters the airway, passes below the vocal cords and no effort is made to eject the material	1 month follow-up visit
Severity of oropharyngeal dysphagia	The severity of oropharyngeal dysphagia will be determined according the penetration-aspiration scale during the videofluoroscopy: Material does not enter the airway.; Material enters the airway. Remains above vocal cords and is ejected from the airway.; Material is above vocal cords and is not ejected from the airway.; Material enters the airway, contacts vocal cords and is ejected from the airway.; Material contacts the vocal cords and is not ejected from the airway.; Material passes below the vocal cords and is ejected into larynx or out of the airway.; Material passes below the vocal cords and is not ejected from the trachea despite effort.; Material enters the airway, passes below the vocal cords and no effort is made to eject the material	3 month follow-up visit
Severity of oropharyngeal dysphagia	The severity of oropharyngeal dysphagia will be determined according the penetration-aspiration scale during the videofluoroscopy: Material does not enter the airway.; Material enters the airway. Remains above vocal cords and is ejected from the airway.; Material is above vocal cords and is not ejected from the airway.; Material enters the airway, contacts vocal cords and is ejected from the airway.; Material contacts the vocal cords and is not ejected from the airway.; Material passes below the vocal cords and is ejected into larynx or out of the airway.; Material passes below the vocal cords and is not ejected from the trachea despite effort.; Material enters the airway, passes below the vocal cords and no effort is made to eject the material	6 month follow-up visit
Safety impairment signs	Prevalence of safety impairment signs (penetrations and/or aspirations) according to videofluoroscopic results	Pre treatment visit
Safety impairment signs	Prevalence of safety impairment signs (penetrations and/or aspirations) according to videofluoroscopic results	1 month follow-up visit
Safety impairment signs	Prevalence of safety impairment signs (penetrations and/or aspirations) according to videofluoroscopic results	3 month follow-up visit
Safety impairment signs	Prevalence of safety impairment signs (penetrations and/or aspirations) according to videofluoroscopic results	6 month follow-up visit
Efficacy impairment signs	Prevalence of efficacy impairment signs (oral and pharyngeal residue) according to videofluoroscopic results	Pre treatment visit
Efficacy impairment signs	Prevalence of efficacy impairment signs (oral and pharyngeal residue) according to videofluoroscopic results	1 month follow-up visit
Efficacy impairment signs	Prevalence of efficacy impairment signs (oral and pharyngeal residue) according to videofluoroscopic results	3 month follow-up visit
Efficacy impairment signs	Prevalence of efficacy impairment signs (oral and pharyngeal residue) according to videofluoroscopic results	6 month follow-up visit
Swallow biomechanics	Measurement of the timing of oropharyngeal swallow response during the videofluoroscopy: Time to laryngeal vestibule closure; Time to upper esophageal sphincter opening; Time to laryngeal vestibule opening	Pre treatment visit
Swallow biomechanics	Measurement of the timing of oropharyngeal swallow response during the videofluoroscopy: Time to laryngeal vestibule closure; Time to upper esophageal sphincter opening; Time to laryngeal vestibule opening	1 month follow-up visit
Swallow biomechanics	Measurement of the timing of oropharyngeal swallow response during the videofluoroscopy: Time to laryngeal vestibule closure; Time to upper esophageal sphincter opening; Time to laryngeal vestibule opening	3 month follow-up visit
Swallow biomechanics	Measurement of the timing of oropharyngeal swallow response during the videofluoroscopy: Time to laryngeal vestibule closure; Time to upper esophageal sphincter opening; Time to laryngeal vestibule opening	6 month follow-up visit
Pharyngeal sensory evoked potential (pSEP)	pSEP will be recorded with a 32-electrode EEG recording cap (10/20 system) during a series of electrical stimuli applied to the pharynx with an intra-pharyngeal catheter.	Pre treatment visit
Pharyngeal sensory evoked potential (pSEP)	pSEP will be recorded with a 32-electrode EEG recording cap (10/20 system) during a series of electrical stimuli applied to the pharynx with an intra-pharyngeal catheter.	1 month follow-up visit
Pharyngeal sensory evoked potential (pSEP)	pSEP will be recorded with a 32-electrode EEG recording cap (10/20 system) during a series of electrical stimuli applied to the pharynx with an intra-pharyngeal catheter.	3 month follow-up visit
Pharyngeal sensory evoked potential (pSEP)	pSEP will be recorded with a 32-electrode EEG recording cap (10/20 system) during a series of electrical stimuli applied to the pharynx with an intra-pharyngeal catheter.	6 month follow-up visit
Pharyngeal motor evoked potentials (pMEP)	pMEPs for both brain hemispheres will be recorded with an intra-pharyngeal catheter by applying 10 pulses of transcraneal magnetic stimulus to each hotspot (tenar and pharyngeal).	Pre treatment visit
Pharyngeal motor evoked potentials (pMEP)	pMEPs for both brain hemispheres will be recorded with an intra-pharyngeal catheter by applying 10 pulses of transcraneal magnetic stimulus to each hotspot (tenar and pharyngeal).	1 month follow-up visit
Pharyngeal motor evoked potentials (pMEP)	pMEPs for both brain hemispheres will be recorded with an intra-pharyngeal catheter by applying 10 pulses of transcraneal magnetic stimulus to each hotspot (tenar and pharyngeal).	3 month follow-up visit
Pharyngeal motor evoked potentials (pMEP)	pMEPs for both brain hemispheres will be recorded with an intra-pharyngeal catheter by applying 10 pulses of transcraneal magnetic stimulus to each hotspot (tenar and pharyngeal).	6 month follow-up visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spontaneous swallowing frequency (SSF)	SSF will be measured with surface neck electromyography and accelerometry for 10min to assess: the number of swallows per minute	Pre treatment visit and 1, 3 and 6 month follow-up visits
Clinical outcomes: Hospital readmission rate	Hospital readmissions (readmissions/100 persons-year)	Pre treatment visit and 1, 3 and 6 month follow-up visits
Clinical outcomes: Prevalence of lower respiratory tract infections	Lower respiratory tract infections (including pneumonia)	Pre treatment visit and 1, 3 and 6 month follow-up visits
Clinical outcomes: Mortality	Mortality rate	Pre treatment visit and 1, 3 and 6 month follow-up visits
Responders rate	Responders were defined as those patients who, after treatment, achieved safe swallow at a lower level of viscosity or, at the same viscosity level, improved at least one point in the penetration-aspiration scale.	6 month follow-up visit
Treatment palatability: Taste	Facial scales on the palatability of the treatment will be performed from V2 to V4. Participants will be asked to respond to questions about the taste using the Face Likert scale: 1. Awful; 2. Not very good; 3. Okay; 4. Really good; 5. Fantastic.	1, 3 and 6 month follow-up visits
Treatment palatability: Texture	Facial scales on the palatability of the treatment will be performed from V2 to V4. Participants will be asked to respond to questions about the texture using the Face Likert scale: 1. Awful; 2. Not very good; 3. Okay; 4. Really good; 5. Fantastic.	1, 3 and 6 month follow-up visits
Treatment palatability: Future Adherence	Facial scales on the palatability of the treatment will be performed from V2 to V4. Participants will be asked to respond to questions about the possible future adherence to the treatment if prescribed using the Face Likert scale: 1. Awful; 2. Not very good; 3. Okay; 4. Really good; 5. Fantastic.	1, 3 and 6 month follow-up visits
Salivary neuropeptides	Saliva samples will be collected in all study visits using the Salivette® technique, by putting a swab under the tongue for 5 min. The concentration of salivary neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) will be determined by using 2 specific commercial Enzyme-Linked ImmunoSorbent Assay (ELISA) kits	1, 3 and 6 month follow-up visits
Treatment safety	Adverse events occurring during the study will be monitored according to the guideline of categories described by the world health organization	From the inclusion to the study until the end of their participation (6 month)
Treatment compliance	A sample of urine will be collected at each study visit and the concentration of riboflavin (part of the composition of the product from the 3 groups) will be extrapolated with fluorescence.	Pre treatment visit and 1, 3 and 6 month follow-up visits

Collaborators and Investigators

• Sponsor: Hospital de Mataró

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: May 23, 2023
• First Submitted That Met QC Criteria: July 14, 2023
• First Posted (Estimated): July 24, 2023

Study Record Updates

• Last Update Posted (Estimated): July 24, 2023
• Last Update Submitted That Met QC Criteria: July 14, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Rehabilitation; TRP agonists; Sensory stimulation
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Pharyngeal Diseases; Otorhinolaryngologic Diseases; Esophageal Diseases; Deglutition Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Sensory System Agents; Dermatologic Agents; Cytochrome P-450 Enzyme Inhibitors; Antipruritics; Capsaicin; Piperine
• Other Study ID Numbers: PI22/01101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No