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

NCT05958173 | Unknown

• 1 other identifier: PI22/01101
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Oropharyngeal Dysphagia; Swallowing Disorder

Keywords

TRP agonists; Sensory stimulation; Rehabilitation

Outcome Measures

Primary Outcomes (24)

• Severity of oropharyngeal dysphagia

  The severity of oropharyngeal dysphagia will be determined according the penetration-aspiration scale during the videofluoroscopy: 1. Material does not enter the airway. 2. Material enters the airway. Remains above vocal cords and is ejected from the airway. 3. Material is above vocal cords and is not ejected from the airway. 4. Material enters the airway, contacts vocal cords and is ejected from the airway. 5. Material contacts the vocal cords and is not ejected from the airway. 6. Material passes below the vocal cords and is ejected into larynx or out of the airway. 7. Material passes below the vocal cords and is not ejected from the trachea despite effort. 8. 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: 1. Material does not enter the airway. 2. Material enters the airway. Remains above vocal cords and is ejected from the airway. 3. Material is above vocal cords and is not ejected from the airway. 4. Material enters the airway, contacts vocal cords and is ejected from the airway. 5. Material contacts the vocal cords and is not ejected from the airway. 6. Material passes below the vocal cords and is ejected into larynx or out of the airway. 7. Material passes below the vocal cords and is not ejected from the trachea despite effort. 8. 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: 1. Material does not enter the airway. 2. Material enters the airway. Remains above vocal cords and is ejected from the airway. 3. Material is above vocal cords and is not ejected from the airway. 4. Material enters the airway, contacts vocal cords and is ejected from the airway. 5. Material contacts the vocal cords and is not ejected from the airway. 6. Material passes below the vocal cords and is ejected into larynx or out of the airway. 7. Material passes below the vocal cords and is not ejected from the trachea despite effort. 8. 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: 1. Material does not enter the airway. 2. Material enters the airway. Remains above vocal cords and is ejected from the airway. 3. Material is above vocal cords and is not ejected from the airway. 4. Material enters the airway, contacts vocal cords and is ejected from the airway. 5. Material contacts the vocal cords and is not ejected from the airway. 6. Material passes below the vocal cords and is ejected into larynx or out of the airway. 7. Material passes below the vocal cords and is not ejected from the trachea despite effort. 8. 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 Outcomes (11)

• Spontaneous swallowing frequency (SSF)

  Pre treatment visit and 1, 3 and 6 month follow-up visits

• Clinical outcomes: Hospital readmission rate

  Pre treatment visit and 1, 3 and 6 month follow-up visits

• Clinical outcomes: Prevalence of lower respiratory tract infections

  Pre treatment visit and 1, 3 and 6 month follow-up visits

• Clinical outcomes: Mortality

  Pre treatment visit and 1, 3 and 6 month follow-up visits

• Responders rate

  6 month follow-up visit

Study Arms (3)

Capsaicin

ACTIVE COMPARATOR

Natural TRPV1 agonist at a concentration of 10mcM. Posology: 10 mL every 8h for 6 month.

Dietary Supplement: Capsaicin

Piperine

ACTIVE COMPARATOR

Natural TRPA1/V1 agonist at a concentration of 150mcM. Posology: 10 mL every 8h for 6 month.

Dietary Supplement: Piperine

Placebo

PLACEBO COMPARATOR

Deionized water + the same preservatives as in the active treatments

Dietary Supplement: Placebo

Interventions

Capsaicin DIETARY_SUPPLEMENT

Oral stimulation with natural TRPV1 agonist

Capsaicin

Piperine DIETARY_SUPPLEMENT

Oral stimulation with natural TRPA1/V1 agonist

Piperine

Placebo DIETARY_SUPPLEMENT

Oral stimulation with placebo solution

Placebo

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• ≥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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Hospital de Mataró: lead

Study Sites (1)

Hospital de Mataró

Mataró, Barcelona, 08304, Spain

Location

MeSH Terms

Conditions

Deglutition Disorders

Interventions

Capsaicin; piperine

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Pere Clavé, PhD

CONTACT

937417700; pere.clave@ciberehd.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The products will be prepared in the Pharmacy Department and will be labeled with a code that does not allow its identification neither by the patient nor by the investigator who administers it.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Single-center, double-blinded, three-arm randomized clinical trial

Study Record Dates

• First Submitted: May 23, 2023
• First Posted: July 24, 2023
• Study Start: September 1, 2023
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: July 24, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)