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

Swallowing Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05958173
• Other study ID #: PI22/01101
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 1, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: July 2023
• Source: Hospital de Mataró
• Contact: Pere Clavé, PhD
• Phone: 937417700
• Email: pere.clave[@]ciberehd.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 150
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 70 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Deglutition Disorders
• Oropharyngeal Dysphagia
• Swallowing Disorder

Intervention

Dietary Supplement:
• Capsaicin
Oral stimulation with natural TRPV1 agonist
• Piperine
Oral stimulation with natural TRPA1/V1 agonist
• Placebo
Oral stimulation with placebo solution

Locations

Country	Name	City	State
Spain	Hospital de Mataró	Mataró	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Hospital de Mataró

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Safety impairment signs	Prevalence of safety impairment signs (penetrations and/or aspirations) according to videofluoroscopic results	Pre treatment visit
Primary	Safety impairment signs	Prevalence of safety impairment signs (penetrations and/or aspirations) according to videofluoroscopic results	1 month follow-up visit
Primary	Safety impairment signs	Prevalence of safety impairment signs (penetrations and/or aspirations) according to videofluoroscopic results	3 month follow-up visit
Primary	Safety impairment signs	Prevalence of safety impairment signs (penetrations and/or aspirations) according to videofluoroscopic results	6 month follow-up visit
Primary	Efficacy impairment signs	Prevalence of efficacy impairment signs (oral and pharyngeal residue) according to videofluoroscopic results	Pre treatment visit
Primary	Efficacy impairment signs	Prevalence of efficacy impairment signs (oral and pharyngeal residue) according to videofluoroscopic results	1 month follow-up visit
Primary	Efficacy impairment signs	Prevalence of efficacy impairment signs (oral and pharyngeal residue) according to videofluoroscopic results	3 month follow-up visit
Primary	Efficacy impairment signs	Prevalence of efficacy impairment signs (oral and pharyngeal residue) according to videofluoroscopic results	6 month follow-up visit
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	Clinical outcomes: Hospital readmission rate	Hospital readmissions (readmissions/100 persons-year)	Pre treatment visit and 1, 3 and 6 month follow-up visits
Secondary	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
Secondary	Clinical outcomes: Mortality	Mortality rate	Pre treatment visit and 1, 3 and 6 month follow-up visits
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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