NCT04741620

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
150

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Jan 2019

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 17, 2019

Completed
2 years until next milestone

First Submitted

Initial submission to the registry

January 29, 2021

Completed
7 days until next milestone

First Posted

Study publicly available on registry

February 5, 2021

Completed
1.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 27, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 27, 2022

Completed
Last Updated

July 13, 2022

Status Verified

July 1, 2022

Enrollment Period

3.2 years

First QC Date

January 29, 2021

Last Update Submit

July 12, 2022

Conditions

Keywords

Oropharyngeal dysphagiaTRP agonistsPharmacological stimulationSensory stimulationElderly

Outcome Measures

Primary Outcomes (1)

  • Change in the score of the Penetration Aspiration Scale

    Differences found in the videofluoroscopy Penetration Aspiration Scale (from 1 (safe swallow) to 8 (silent aspiration)) between treatments and vs. the placebo group.

    Baseline versus 2/3 days after the intervention

Secondary Outcomes (11)

  • Impaired safety of swallow

    Baseline versus 2/3 days after the intervention

  • Impaired efficacy

    Baseline versus 2/3 days after the intervention

  • Oropharyngeal swallow response (laryngeal vestibule closure time)

    Baseline versus 2/3 days after the intervention

  • Oropharyngeal swallow response (upper esophageal opening time)

    Baseline versus 2/3 days after the intervention

  • Oropharyngeal swallow response (laryngeal vestibule opening time)

    Baseline versus 2/3 days after the intervention

  • +6 more secondary outcomes

Study Arms (6)

Capsaicin 10microM

ACTIVE COMPARATOR

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

Other: Piperine 150microM (TRPV1 & TRPA1 natural agonist)Other: Cinnamaldehyde 756,6microM + zinc 70microM (TRPA1 natural agonist)Other: Citric acid 457,5microM (pH=3,5) (ASIC3 natural agonist)Other: Capsaicin 10microM + Citric acid 457,5microM (pH=3,5) (TRPV1 & ASIC3 natural agonists)Other: Placebo (Methyl benzoate, Propyl benzoate, Propylenglycol)

Piperine 150microM

ACTIVE COMPARATOR

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

Other: Capsaicin 10microM (TRPV1 natural agonist)Other: Cinnamaldehyde 756,6microM + zinc 70microM (TRPA1 natural agonist)Other: Citric acid 457,5microM (pH=3,5) (ASIC3 natural agonist)Other: Capsaicin 10microM + Citric acid 457,5microM (pH=3,5) (TRPV1 & ASIC3 natural agonists)Other: Placebo (Methyl benzoate, Propyl benzoate, Propylenglycol)

Cinnamaldehyde 756,6microM + zinc 70microM

ACTIVE COMPARATOR

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).

Other: Capsaicin 10microM (TRPV1 natural agonist)Other: Piperine 150microM (TRPV1 & TRPA1 natural agonist)Other: Citric acid 457,5microM (pH=3,5) (ASIC3 natural agonist)Other: Capsaicin 10microM + Citric acid 457,5microM (pH=3,5) (TRPV1 & ASIC3 natural agonists)Other: Placebo (Methyl benzoate, Propyl benzoate, Propylenglycol)

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

ACTIVE COMPARATOR

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).

Other: Capsaicin 10microM (TRPV1 natural agonist)Other: Piperine 150microM (TRPV1 & TRPA1 natural agonist)Other: Cinnamaldehyde 756,6microM + zinc 70microM (TRPA1 natural agonist)Other: Capsaicin 10microM + Citric acid 457,5microM (pH=3,5) (TRPV1 & ASIC3 natural agonists)Other: Placebo (Methyl benzoate, Propyl benzoate, Propylenglycol)

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

ACTIVE COMPARATOR

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).

Other: Capsaicin 10microM (TRPV1 natural agonist)Other: Piperine 150microM (TRPV1 & TRPA1 natural agonist)Other: Cinnamaldehyde 756,6microM + zinc 70microM (TRPA1 natural agonist)Other: Citric acid 457,5microM (pH=3,5) (ASIC3 natural agonist)Other: Placebo (Methyl benzoate, Propyl benzoate, Propylenglycol)

Placebo

PLACEBO COMPARATOR

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

Other: Capsaicin 10microM (TRPV1 natural agonist)Other: Piperine 150microM (TRPV1 & TRPA1 natural agonist)Other: Cinnamaldehyde 756,6microM + zinc 70microM (TRPA1 natural agonist)Other: Citric acid 457,5microM (pH=3,5) (ASIC3 natural agonist)Other: Capsaicin 10microM + Citric acid 457,5microM (pH=3,5) (TRPV1 & ASIC3 natural agonists)

Interventions

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

Capsaicin 10microM + Citric acid 457,5microM (pH=3,5)Cinnamaldehyde 756,6microM + zinc 70microMCitric acid 457,5microM (pH=3,5)Piperine 150microMPlacebo

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

Capsaicin 10microMCapsaicin 10microM + Citric acid 457,5microM (pH=3,5)Cinnamaldehyde 756,6microM + zinc 70microMCitric acid 457,5microM (pH=3,5)Placebo

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

Capsaicin 10microMCapsaicin 10microM + Citric acid 457,5microM (pH=3,5)Citric acid 457,5microM (pH=3,5)Piperine 150microMPlacebo

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

Capsaicin 10microMCapsaicin 10microM + Citric acid 457,5microM (pH=3,5)Cinnamaldehyde 756,6microM + zinc 70microMPiperine 150microMPlacebo

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

Capsaicin 10microMCinnamaldehyde 756,6microM + zinc 70microMCitric acid 457,5microM (pH=3,5)Piperine 150microMPlacebo

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

Capsaicin 10microMCapsaicin 10microM + Citric acid 457,5microM (pH=3,5)Cinnamaldehyde 756,6microM + zinc 70microMCitric acid 457,5microM (pH=3,5)Piperine 150microM

Eligibility Criteria

Age70 Years+
Sexall
Healthy VolunteersNo
Age GroupsOlder Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Consorci Sanitari del Maresme (Hospital de Mataró)

Mataró, Barcelona, 08301, Spain

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Deglutition Disorders

Interventions

methyl benzoate

Condition Hierarchy (Ancestors)

Esophageal DiseasesGastrointestinal DiseasesDigestive System DiseasesPharyngeal DiseasesOtorhinolaryngologic Diseases

Study Officials

  • Pere Clavé, PhD

    Hospital de Mataró

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

January 29, 2021

First Posted

February 5, 2021

Study Start

January 17, 2019

Primary Completion

March 27, 2022

Study Completion

March 27, 2022

Last Updated

July 13, 2022

Record last verified: 2022-07

Data Sharing

IPD Sharing
Will not share

Locations