Effect of a Cooling Sensation Flavor on the Swallow Response in Post-stroke Patients With Oropharyngeal Dysphagia

REFRESH Study: Therapeutic Effect of a Cooling Sensation Flavor in Pre-thickened ONS Products on the Swallow Response in Post-stroke Patients With Oropharyngeal Dysphagia

Current oropharyngeal dysphagia (OD) treatment in older patients is based on compensatory strategies (fluid thickening and texture modified diets) that improve swallow safety but do not improve the swallowing function. One of these strategies is thickening products, which are used to reduce pharyngeal bolus velocity by increasing viscosity of fluids. There are several studies demonstrating the therapeutic effect of thickeners in reducing the prevalence of penetrations and aspirations, and their use has been correlated with reduced prevalence of respiratory infections, aspiration pneumonia and hospital readmissions.

In recent years, new neurorehabilitation treatment strategies for OD have been developed such as peripheral (electrical or chemical stimulation) or central stimulation (transcranial direct current stimulation or repetitive transcranial magnetic stimulation).

The investigators suggest that new generation treatments for OD have to combine thickened fluids and about peripheral stimulation using transient receptor potential (TRP) channels agonists. The aim of this study is to evaluate the therapeutic effect of a cooling sensation (CS) flavor in a pre-thickened oral nutritional supplement (ONS) drink on the biomechanical mechanism of the swallow response in chronic post-stroke patients with OD.

The investigators designed a randomized, crossover, interventional and open-label clinical study. The study includes 2 groups: 1) n=25: 1st visit: stimulation with Control, 2nd visit: stimulation with CS; and 2) n=25: 1st visit: stimulation with CS, 2nd visit: stimulation with Control. Each patient will attend a total of 2 visits, with a washing period of at least 7 days between visits. The procedures to be performed during each visit are: clinical assessment of swallowing with V-VST, spontaneous swallowing frequency measurement using electromyography, and collection of a sample of saliva using a Salivette®.

Study Overview

• Status: Recruiting
• Conditions: Stroke; Oropharyngeal Dysphagia; Swallowing Disorder
• Intervention / Treatment: Dietary supplement: Pre-thickened oral nutritional supplement with a cooling sensation flavour; Dietary supplement: Pre-thickened oral nutritional supplement without a cooling sensation flavour

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pere Clavé, MD, PhD; Phone Number: 2284 937417700; Email: pere.clave@ciberehd.org

Study Locations

• Spain
  • Barcelona
    • Mataró, Barcelona, Spain, 08304
      • Recruiting
      • Hospital de Mataró
      • Contact: Pere Clavé, MD; Phone Number: 2284 937417700; Email: pere.clave@ciberehd.org
      • Principal Investigator: Pere Clavé, MD, PhD
      • Sub-Investigator: Noemí Tomsen, PhD
      • Sub-Investigator: Mireia Bolívar-Prados, PhD
      • Sub-Investigator: Omar Ortega, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥18 years
• Patients with chronic OD as a consequence of stroke (more than 3 month since stroke diagnostic)
• Patients with impaired safety and/or efficacy of swallow (V-VST)
• Patients that can swallow safely the investigation and control product according to the viscosity of the product and the results of the V-VST
• Patients able to follow the protocol and give informed consent

Exclusion Criteria:

• Pregnancy
• Life expectancy <3 months or palliative care
• OD diagnosis prior to stroke
• Dementia (GDS 4 or higher)
• Allergy to the investigation and/or control product or to any of its components
• Participation in another interventional study in the month prior to inclusion
• Current users of a pre-thickened ONS drink with cooling sensation flavor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active; Pre-thickened oral nutritional supplement with a cooling sensation flavour	Dietary supplement: Pre-thickened oral nutritional supplement with a cooling sensation flavour; Pre-thickened oral nutritional supplement (ONS) drink with cooling sensation flavour
Placebo Comparator: Control; Pre-thickened oral nutritional supplement without a cooling sensation flavour	Dietary supplement: Pre-thickened oral nutritional supplement without a cooling sensation flavour; Pre-thickened oral nutritional supplement (ONS) drink without cooling sensation flavour

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pre visit 1 Spontaneous swallowing frequency (SSF)	SSF will be measured with surface neck electromyography (sEMG) and accelerometry for 10min, in which the patient will be asked to breathe normally and to remain calm and quiet. sEMG electrodes will be placed over the digastric-mylohyoid complex and an omnidirectional accelerometer over the cricothyroid cartilage to assess the number of swallows per minute.	Pre intervention in visit 1 (baseline)
Pre visit 1 EMG metrics	EMG metrics (amplitude (Volts), latency (seconds), duration (seconds) and area under the curve (volts·second)) of the recordings using the AcqKnowledge 4.4 software (BIOPAC Systems, USA) will be analyzed and combined to describe the electromyographic response of the suprahyoid muscles.	Pre intervention in visit 1 (baseline)
Post visit 1 Spontaneous swallowing frequency (SSF)	SSF will be measured with surface neck electromyography (sEMG) and accelerometry for 10min, in which the patient will be asked to breathe normally and to remain calm and quiet. sEMG electrodes will be placed over the digastric-mylohyoid complex and an omnidirectional accelerometer over the cricothyroid cartilage to assess the number of swallows per minute.	Post intervention in visit 1 (baseline)
Post visit 1 EMG metrics	EMG metrics (amplitude (Volts), latency (seconds), duration (seconds) and area under the curve (volts·second)) of the recordings using the AcqKnowledge 4.4 software (BIOPAC Systems, USA) will be analyzed and combined to describe the electromyographic response of the suprahyoid muscles.	Post intervention in visit 1 (baseline)
Pre visit 2 Spontaneous swallowing frequency (SSF)	SSF will be measured with surface neck electromyography (sEMG) and accelerometry for 10min, in which the patient will be asked to breathe normally and to remain calm and quiet. sEMG electrodes will be placed over the digastric-mylohyoid complex and an omnidirectional accelerometer over the cricothyroid cartilage to assess the number of swallows per minute.	Pre intervention visit 2 (1 week after)
Pre visit 2 EMG metrics	EMG metrics (amplitude (Volts), latency (seconds), duration (seconds) and area under the curve (volts·second)) of the recordings using the AcqKnowledge 4.4 software (BIOPAC Systems, USA) will be analyzed and combined to describe the electromyographic response of the suprahyoid muscles.	Pre intervention visit 2 (1 week after)
Post visit 2 Spontaneous swallowing frequency (SSF)	SSF will be measured with surface neck electromyography (sEMG) and accelerometry for 10min, in which the patient will be asked to breathe normally and to remain calm and quiet. sEMG electrodes will be placed over the digastric-mylohyoid complex and an omnidirectional accelerometer over the cricothyroid cartilage to assess the number of swallows per minute.	Post intervention visit 2 (1 week after)
Post visit 2 EMG metrics	EMG metrics (amplitude (Volts), latency (seconds), duration (seconds) and area under the curve (volts·second)) of the recordings using the AcqKnowledge 4.4 software (BIOPAC Systems, USA) will be analyzed and combined to describe the electromyographic response of the suprahyoid muscles.	Post intervention visit 2 (1 week after)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Volume-viscosity swallowing test (V-VST)	The V-VST is an effort test in which boluses of increasing volume and viscosity are administered to check for clinical signs of impaired efficacy and safety in each swallow. V-VST is designed to protect patients from aspiration by starting with 250 mPa•s viscosity and increasing volumes from 5 ml, to 10 ml and 20 ml boluses. When patients have completed the 250 mPa•s series without major symptoms of aspiration, a less safe liquid viscosity series will be assessed. Finally, a safer 800 mPa•s viscosity series will be assessed in the same way. If the patient presents signs of impaired safety at 250 mPa•s viscosity, the series will be interrupted, the <50 mPa•s viscosity series will be omitted, and a safer 800 mPa•s viscosity series will be assessed. If the patient presents signs of impaired safety at <50 mPa•s viscosity, the liquid series will be interrupted, and the 800 mPa•s series will be assessed.	Pre and Post treatment in visit 1 (baseline) and visit 2 (1 week after)
Concentration of salivary neuropeptides	Saliva samples will be collected using the Salivette® technique, by putting a swab under the tongue for 5 min. Samples will be stored at -80ºC until their analysis. 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: Substance P Parameter Assay Kit (R&D systems, USA) and CGRP (Human) ELISA kit (Abnova, Taiwan).	Pre and Post treatment in visit 1 (baseline) and visit 2 (1 week after)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterization of the rheological properties of the study products	Determination of the viscosity in mPa•s at 50s-1 and the effect of the shear rate (viscosity at 50s-1 and at 300s-1) and alpha-amylase will be determine for both products. The rheological data will ensure the safety of the patients with OD during the study procedures.	Previous to the start of the clinical study

Collaborators and Investigators

• Sponsor: Hospital de Mataró
• Collaborators: Nutricia Research

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2023
• Primary Completion (Estimated): January 31, 2025
• Study Completion (Estimated): January 31, 2025

Study Registration Dates

• First Submitted: July 6, 2023
• First Submitted That Met QC Criteria: January 31, 2024
• First Posted (Estimated): February 9, 2024

Study Record Updates

• Last Update Posted (Estimated): February 9, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Gastrointestinal Diseases; Pharyngeal Diseases; Otorhinolaryngologic Diseases; Esophageal Diseases; Stroke; Deglutition Disorders
• Other Study ID Numbers: Refresh

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No