Effects of 6-month of Treatment With TRPV1 and TRPA1 Agonists in Older Patients With OD
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Study Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- Severity of oropharyngeal dysphagia [Pre treatment visit]
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
- Severity of oropharyngeal dysphagia [1 month follow-up visit]
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
- Severity of oropharyngeal dysphagia [3 month follow-up visit]
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
- Severity of oropharyngeal dysphagia [6 month follow-up visit]
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
- Safety impairment signs [Pre treatment visit]
Prevalence of safety impairment signs (penetrations and/or aspirations) according to videofluoroscopic results
- Safety impairment signs [1 month follow-up visit]
Prevalence of safety impairment signs (penetrations and/or aspirations) according to videofluoroscopic results
- Safety impairment signs [3 month follow-up visit]
Prevalence of safety impairment signs (penetrations and/or aspirations) according to videofluoroscopic results
- Safety impairment signs [6 month follow-up visit]
Prevalence of safety impairment signs (penetrations and/or aspirations) according to videofluoroscopic results
- Efficacy impairment signs [Pre treatment visit]
Prevalence of efficacy impairment signs (oral and pharyngeal residue) according to videofluoroscopic results
- Efficacy impairment signs [1 month follow-up visit]
Prevalence of efficacy impairment signs (oral and pharyngeal residue) according to videofluoroscopic results
- Efficacy impairment signs [3 month follow-up visit]
Prevalence of efficacy impairment signs (oral and pharyngeal residue) according to videofluoroscopic results
- Efficacy impairment signs [6 month follow-up visit]
Prevalence of efficacy impairment signs (oral and pharyngeal residue) according to videofluoroscopic results
- Swallow biomechanics [Pre treatment visit]
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
- Swallow biomechanics [1 month follow-up visit]
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
- Swallow biomechanics [3 month follow-up visit]
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
- Swallow biomechanics [6 month follow-up visit]
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
- Pharyngeal sensory evoked potential (pSEP) [Pre treatment visit]
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.
- Pharyngeal sensory evoked potential (pSEP) [1 month follow-up visit]
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.
- Pharyngeal sensory evoked potential (pSEP) [3 month follow-up visit]
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.
- Pharyngeal sensory evoked potential (pSEP) [6 month follow-up visit]
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.
- Pharyngeal motor evoked potentials (pMEP) [Pre treatment visit]
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).
- Pharyngeal motor evoked potentials (pMEP) [1 month follow-up visit]
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).
- Pharyngeal motor evoked potentials (pMEP) [3 month follow-up visit]
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).
- Pharyngeal motor evoked potentials (pMEP) [6 month follow-up visit]
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).
Secondary Outcome Measures
- Spontaneous swallowing frequency (SSF) [Pre treatment visit and 1, 3 and 6 month follow-up visits]
SSF will be measured with surface neck electromyography and accelerometry for 10min to assess: the number of swallows per minute
- Clinical outcomes: Hospital readmission rate [Pre treatment visit and 1, 3 and 6 month follow-up visits]
Hospital readmissions (readmissions/100 persons-year)
- Clinical outcomes: Prevalence of lower respiratory tract infections [Pre treatment visit and 1, 3 and 6 month follow-up visits]
Lower respiratory tract infections (including pneumonia)
- Clinical outcomes: Mortality [Pre treatment visit and 1, 3 and 6 month follow-up visits]
Mortality rate
- Responders rate [6 month follow-up visit]
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.
- Treatment palatability: Taste [1, 3 and 6 month follow-up visits]
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.
- Treatment palatability: Texture [1, 3 and 6 month follow-up visits]
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.
- Treatment palatability: Future Adherence [1, 3 and 6 month follow-up visits]
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.
- Salivary neuropeptides [1, 3 and 6 month follow-up visits]
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
- Treatment safety [From the inclusion to the study until the end of their participation (6 month)]
Adverse events occurring during the study will be monitored according to the guideline of categories described by the world health organization
- Treatment compliance [Pre treatment visit and 1, 3 and 6 month follow-up visits]
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.
Eligibility Criteria
Criteria
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).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hospital de Mataró | Mataró | Barcelona | Spain | 08304 |
Sponsors and Collaborators
- Hospital de Mataró
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PI22/01101