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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 10ĀµM (TRPV1 agonist), 2) piperine 150ĀµM (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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Capsaicin | Active Comparator | Natural TRPV1 agonist at a concentration of 10mcM. Posology: 10 mL every 8h for 6 month. |
|
| Piperine | Active Comparator | Natural TRPA1/V1 agonist at a concentration of 150mcM. Posology: 10 mL every 8h for 6 month. |
|
| Placebo | Placebo Comparator | Deionized water + the same preservatives as in the active treatments |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Capsaicin | Dietary Supplement | Oral stimulation with natural TRPV1 agonist |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Severity of oropharyngeal dysphagia | The severity of oropharyngeal dysphagia will be determined according the penetration-aspiration scale during the videofluoroscopy:
| Pre treatment visit |
| Severity of oropharyngeal dysphagia | The severity of oropharyngeal dysphagia will be determined according the penetration-aspiration scale during the videofluoroscopy:
| 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:
|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Pere ClavƩ, PhD | Contact | 937417700 | 2284 | pere.clave@ciberehd.org |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital de MatarĆ³ | MatarĆ³ | Barcelona | 08304 | Spain |
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| ID | Term |
|---|---|
| D003680 | Deglutition Disorders |
| ID | Term |
|---|---|
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D010608 | Pharyngeal Diseases |
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| ID | Term |
|---|---|
| D002211 | Capsaicin |
| C008922 | piperine |
| ID | Term |
|---|---|
| D053284 | Polyunsaturated Alkamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D000475 | Alkenes |
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Single-center, double-blinded, three-arm randomized clinical trial
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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.
| Piperine |
| Dietary Supplement |
Oral stimulation with natural TRPA1/V1 agonist |
|
| Placebo | Dietary Supplement | Oral stimulation with placebo solution |
|
| 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:
| 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:
| Pre treatment visit |
| Swallow biomechanics | Measurement of the timing of oropharyngeal swallow response during the videofluoroscopy:
| 1 month follow-up visit |
| Swallow biomechanics | Measurement of the timing of oropharyngeal swallow response during the videofluoroscopy:
| 3 month follow-up visit |
| Swallow biomechanics | Measurement of the timing of oropharyngeal swallow response during the videofluoroscopy:
| 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 |
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 SalivetteĀ® 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 |
| D010038 | Otorhinolaryngologic Diseases |
| D006839 |
| Hydrocarbons, Acyclic |
| D006838 | Hydrocarbons |
| D002396 | Catechols |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D012991 | Solanaceous Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D005229 | Fatty Acids, Monounsaturated |
| D005231 | Fatty Acids, Unsaturated |
| D005227 | Fatty Acids |
| D008055 | Lipids |