Physiological Flow of Liquids in Head and Neck Cancer Patients: A Pilot Study
Conditions: Deglutition Disorders, Oropharynx Cancer
Sponsor: University Health Network, Toronto

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Ethics Protocol 
 
Title:  
Physiological Flow of Liquids in Head and Neck Cancer Patients: A Pilot Study 
NCT04112940 
Principal Investigator: Catriona M. Steele, Ph.D. (Toronto Rehabilitation Institute) 
 
 
 
Douglas B. Chepeha, MD, MScPH, FACS, FRCS(C) 
 
 
 
Andrew J. Hope, MD, FRCPC 
 
 
 
 
 
 
 

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Table of Contents 
 
1. 
Introduction .......................................................................................................................................... 3 
2. 
Purpose and Specific Aims .................................................................................................................... 3 
3. 
Methods ................................................................................................................................................ 4 
4. 
Risks and Benefits ................................................................................................................................. 9 
5. 
Privacy and Confidentiality ................................................................................................................. 10 
6. 
Compensation ..................................................................................................................................... 10 
7. 
Conflicts of Interest ............................................................................................................................. 11 
8. 
Informed Consent Process .................................................................................................................. 11 
9. 
Scholarly Review ................................................................................................................................. 11 
10. 
Additional Ethics Reviews ............................................................................................................... 11 
11. 
Contracts ......................................................................................................................................... 12 
12. 
Budget ............................................................................................................................................. 12 
 
 
 
 
 
 
 
 
 
 
 
 

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1. 
Introduction 
This protocol covers a subproject of a larger project entitled Physiological Flow of Liquids Used in 
Dysphagia Management. The larger project (henceforth referred to as the parent grant) has been 
reviewed and funded by the National Institutes of Health as a 5-year R01 grant awarded to the PI 
(Catriona Steele, Ph.D). 
The overall goal of the parent grant is to collect measurements of liquid flow through the oropharynx 
(i.e., mouth and throat) during swallowing. The factors that are expected to influence liquid flow include 
the liquid consistency (i.e., thin, slightly-thick, mildly-thick, moderately-thick, extremely-thick) and the 
forces applied during swallowing (i.e., tongue pressures and swallowing muscle contraction). The 
overarching objective is to determine how these factors interact to influence the flow of a liquid through 
the oropharynx.  The goal of this subproject is to explore this question in adults with head and neck 
cancer.  
Work on the parent grant to date has included the development, characterization and testing of liquid 
stimuli to be used in the current project, in which measures of liquid flow and swallowing behaviour will 
be collected in patients with head and neck cancer. Data collection will take place at the Swallowing 
Rehabilitation Research Lab of the Toronto Rehabilitation Institute. Videofluoroscopy x-rays will be 
conducted on a purchased service basis in the diagnostic imaging department at the Toronto General 
Hospital. We will also use patient questionnaires to evaluate the acceptability of thickened liquids by 
people with head and neck cancer.  
2. 
Purpose and Specific Aims 
Dysphagia (swallowing impairment) involves two primary concerns: 1) the ability to swallow safely, 
without material entering the airway; 2) the ability to swallow efficiently, without leaving residue behind 
in the pockets of the pharynx. Impaired swallowing safety is linked to pneumonia while impaired 
efficiency contributes to risk of malnutrition. Dysphagia is common in patients with head and neck 
cancer prior to, and as a result of treatment. Radiation treatment for the cancer can cause and 
exacerbate symptoms of dysphagia. Due to an increase in the prevalence of oropharyngeal cancers 
secondary to the Human Papilloma Virus (HPV), a growing number of individuals are receiving radiation 
treatment for their disease. However, because of the typically young age at diagnosis, these individuals 
can expect longer post-treatment lifespans during which there is a significant chance for negative 
sequelae to develop, including dysphagia. When a person presents with dysphagia, a common 
intervention is to alter the consistency of the foods and fluids they consume. However, we lack evidence 
to guide the modification of food and liquid textures for clinical benefit. In particular, we lack studies 
demonstrating the effect of texture modification as an intervention in the head and neck cancer 
population.  In this study, we propose to measure the flow of thin, slightly thick and mildly thick liquids 
in patients who have completed radiation treatment for base of tongue cancer, to understand whether 
or not thickened liquids provide benefit.   

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We have three specific aims:  
Aim 1: To determine whether slightly-thick and mildly-thick liquids are palatable and acceptable to 
patients with base of tongue cancer. We will collect palatability measures for starch- and gum-
thickened liquids with slightly-thick and mildly-thick consistencies, as defined by the International 
Dysphagia Diet Standardisation Initiative syringe flow test.  We will also collect baseline quality of life 
measures to understand the impact of swallowing impairment on the participant’s quality of life. 
Following a videofluoroscopy swallowing assessment (described under Aim 2), participants will be 
advised to use thickened liquids that are effective for improving their swallowing.  A follow-up phone 
call will monitor compliance and acceptance of this recommendation. Significance: This will determine 
how likely participants are to adhere to a thickener recommended based on its efficacy to reduce 
aspiration.  
 
Aim 2: To determine how slightly-thick and mildly-thick liquids flow and whether they reduce 
aspiration compared to thin liquids in patients with base of tongue cancer. We will collect concurrent 
videofluoroscopic  x-rays of swallowing and physiological measures of tongue pressure in patients with 
head and neck cancer using thin, slightly- and mildly-thick liquid barium stimuli. This appointment will 
occur approximately 3-6 months after the completion of the participants’ radiation schedule. 
Significance: This will demonstrate the impact of consistency on bolus flow through the mouth and 
pharynx, controlling for the forces used to initiate flow and propel the bolus. Additionally, the data 
collected will aid in characterizing  swallow physiology after completion of radiation therapy.  
 
Aim 3: To determine whether the use of starch vs. gum thickeners impact the results of aims 1 and 2 
The thickened liquids used for aims 1 and 2 will be prepared using both starch- and gum-based 
thickeners. Additionally, we will collect measures of salivary flow to control for possible interactions 
between thickener type and oral dryness on the results.  Significance: Individuals may find one thickener 
more palatable or comfortable to swallow.  Understanding this may impact compliance, swallowing 
safety and quality of life.  
3. 
Methods 
Participants:  
The protocol will involve a single sample of adults, aged 18 or older with an initial cancer diagnosis of 
base of tongue cancer (T1-T3, N0-N2c, HPV + or -). The eligibility criteria will include completion of 
bilateral radiation therapy to the neck 3 months prior to enrollment, and removal of enteral feeding 
tube. 
Participants will be asked to attend appointments and complete all data collection sessions described in 
this protocol. Participation involves two appointments, and two follow-up phone calls.  
 

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Exclusion Criteria:  
 
Participants will be accepted into the study provided they have no previous health condition 
known to cause swallowing impairment (e.g., stroke; brain injury; neurodegenerative disease). 
 
Individuals with a previous history of radiation to the head and/or neck area (prior to the 
current radiation treatment) will be excluded from this study given the possibility of long-term 
radiation effects to the swallowing apparatus.  
 
Individuals with a previous cancer diagnosis will be excluded from the study. 
 
Participants who do not show impaired swallowing safety on thin liquids in the videofluoroscopy 
(Penetration Aspiration Scale scores of 1 and 2) will be withdrawn from the study. 
 
Participants who have had, or have a planned neck dissection will be excluded.  
 
Individuals with tracheostomy in situ will be excluded from the study.  
 
Individuals with cognitive communication difficulties that preclude the understanding of the 
protocol or following study instructions will be excluded from the study. 
 
Due to the requirement to swallow stimuli containing starch based thickeners, which carry a 
significant carbohydrate load, individuals with Type 1 Diabetes will be excluded. 
 
Individuals with known allergies to latex, dental glue or barium will be excluded, due to the 
probability that these items will come into contact with the oral mucosa during data collection.  
 
Children and pregnant women will be excluded from the study due to the use of radiation 
 
Occupational exposure to radiation exceeding half the limit specified for Ontario exposed 
workers within the past 12 months. 
These exclusion criteria will be confirmed using a self-report questionnaire form at the time of intake 
into the study (see standard operating procedures [SOP], provided as an additional study document). 
Any questions will be clarified through discussion with the research assistant responsible for participant 
intake, and, where necessary with the principal investigator.  
 
Recruitment:  
This is a preliminary study that will demonstrate feasibility for a future planned extension.  We propose 
to recruit 10-12 participants. Potential participants will be identified by study Co-PIs Dr. Andrew Hope 
and Dr. Douglas Chepeha through the current radiation therapy clinics and base of tongue cancer 
caseloads at Princess Margaret Cancer Centre. 
 
Stimuli:  
An array of barium and non-barium stimuli has been developed for this study. These stimuli include thin, 
slightly-thick and mildly-thick liquids, defined using the International Dysphagia Diet Standardisation 
Initiative (IDDSI) gravity flow measures. The barium stimuli used for videofluoroscopy will be prepared 
using E-Z-Paque® barium in 20% w/v barium concentration with starch and gum-based thickening agents 
(Nestlé Resource® ThickenUp® and ThickenUp Clear®). The non-barium stimuli will be prepared using 
Nestle’s Lemon Spash® lemon-flavoured water and the same starch and gum-based thickening agents 

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(Nestlé Resource® ThickenUp® and ThickenUp Clear®).  All stimuli will be prepared in the Swallowing 
Rehabilitation Research Laboratory not longer than 6 hours prior to scheduled use, according to a strict 
standard operating procedure (refer to additional reference documents). Following preparation, stimuli 
will be stored in the swallowing lab until needed. Barium stimuli will be transported to the radiology 
suite at Toronto General Hospital in a cooler, as per routine clinical procedures.  
 
Data to be collected from each participant:  
The following types of data will be collected from participants: 
a) An intake questionnaire noting age, sex, ethnicity and race data and confirming eligibility 
based on the absence of reported exclusion criteria.  
b) During the intake process, we will review a list of conditions that could alter the results of 
the research study and identify whether any of these conditions apply. This will include 
disclosing the use of any medications that the participant is are currently taking, in order to 
allow us to control for the possible influence of medication on oral sensory and motor 
function.  Medications do not qualify as the basis for exclusion. However, it is important for 
us to collect information regarding the use of benzodiazepines and neuroleptic medications 
that are known to have possible effects on swallowing, particularly with respect to causing 
xerostomia (dry mouth).  
c) Palatability ratings for thickened liquids (with barium and without barium). 
d) The MD Anderson Dysphagia Inventory (a quality of life scale related to dysphagia) 
e) The Performance Status Scale – Head and Neck (a scale capturing dysphagia and diet status) 
f) The University of Washington Quality of Life Revised Version 4 (UW-WOL-R4). 
g) Tongue-pressure waveform data, collected at the anterior, middle and posterior palate 
using the 3-bulb tongue-pressure bulb array of the KayPENTAX Swallowing Signals Lab.If the 
participant is unable to tolerate the attachment of the sensors, we will measure tongue 
strength using the Iowa Oral Performance Instrument (IOPI). This approach does not include 
adhered attachments to the oral mucosa. 
h) A measure of stimulated saliva (the Saxon Test), using a 2x2 inch of folded gauze that is 
chewed for 2 minutes, expectorated  and then weighed prior to being discarded. 
i) 
A videofluoroscopy recording of swallowing collected at a pulse rate of 30 pulses per second 
and video capture at 30 frames per second.  
j) 
Responses to follow-up phone calls exploring acceptance of thickened liquids. 
Data Collection Procedures: Data Collection Session 1: The participant will arrive at the lab and will be 
asked to complete two questionnaires:  the MD Anderson Dysphagia Inventory (MDADI), the 
Performance Status Scale for Head and Neck Cancer (PSS-HN) and the University of Washington Quality 
of Life Revised Version 4 (UW-WOL-R4). 
Prior to data collection, saliva flow will be collected using the Saxon Test, for which the participant will 
chew on folded sterile gauze for 2 minutes. The gauze will be weighed before and after chewing to 
determine amount of saliva production. The participant will then be asked to swallow 6 non-barium 

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stimuli, and 2 barium stimuli thickened using starch and xanthan-gum based thickeners. After the 
participant has sampled each stimulus, they will be asked to rate palatability on a visual, hedonic scale 
(see study instruments provided). 
 
Data Collection Session 2: Prior to data collection, saliva flow will be collected using the Saxon Test, for 
which the participant will chew on folded sterile gauze for 2 minutes. The gauze will be weighed before 
and after chewing to determine amount of saliva production. The participant will then be seated in the 
videofluoroscopy suite for tongue pressure sensor attachment. A silicon strip housing three 8 mm 
diameter pressure bulbs will be attached in midline to the roof of the participant’s mouth, with the front 
sensor located immediately behind the participant’s upper incisor teeth. The sensor strip will be 
attached using a medical adhesive (Stomahesive®, Convatec, St-Laurent, Quebec, Canada).  
Following sensor attachment, the video 
output line from the fluoroscopy unit and the 
tongue pressure sensors will then be 
connected to the KayPENTAX Digital 
Swallowing Workstation Swallowing Signals 
Lab equipment, which is located on a properly 
insulated cart with an uninterrupted power 
supply and isolation transformer (see Image  
1). If the participant is unable to tolerate the 
attachment of the sensors due to mucositis or 
general discomfort, we will measure tongue 
strength using the Iowa Oral Performance Instrument (IOPI) and collect the videofluoroscopy measures 
without the use of the adhered sensors.  
 
Participants will be asked to swallow a series of thin, slightly-thick and mildly-thick barium stimuli 1 (3 
boluses each of 5 stimuli, for a total of 15 boluses) in videofluoroscopy, with concurrent measurement 
of tongue-palate pressure. Videofluoroscopy will be performed at optimal temporal resolution (30 
pulses/second) and captured at 30 frames/second. The stimuli will be presented in a randomized design, 
blocked by stimulus type. Participants will be allowed to take natural sized sips of each stimulus from 
cups containing 40 ml. Sip volume and mass will be calculated, by weighing the cups prior to and after 
the videofluoroscopic assessment.  
 
Data Processing:   
The tongue-pressure waveform will be segmented using an automatic segmentation algorithm 
developed previously in the PI’s lab. Similarly, the videofluoroscopy recordings will be spliced into single 
bolus clips and the audio channel will be muted to remove cues that might bias rating. Blinded 
videofluoroscopy rating will then be performed in duplicate by trained raters in the Steele Lab following 
established procedures (see SOP provided as an additional study document). Discrepancies between 
raters will be flagged and resolved at consensus meetings, as required. These procedures will yield a 
Image 1.  Tongue pressure sensors. 

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large number of parameters for each swallow. We will use established measures within our lab to collect 
and analyze measures related to kinematics and residue.  
Follow-up phone calls: If deemed appropriate, the participant may be offered the opportunity to 
complete a follow-up component. For those willing to participate, this optional experiment will involve 
two follow-up telephone calls (at 2 weeks and 3 months following the videofluoroscopy) to determine 
compliance with use of thickened liquids recommended following the videofluoroscopy (see study 
instruments provided for questionnaires).   
Data Analysis:  
For Aim 1, we will compare hedonic ratings for the different stimuli using a univariate ANOVA.  It is 
hypothesized that ratings will be significantly better for the thin and slightly thick stimuli compared to 
the mildly-thick stimuli, and that a preference will be seen for the gum compared to the starch 
thickened liquids. 
For Aim 2, blinded videofluoroscopy rating will be performed in duplicate, and discrepancies between 
raters will be flagged and resolved at a consensus meeting. The frequency of aspiration will be explored 
with the thin stimuli and compared to the prevalence of aspiration when thickeners are introduced 
using chi-square statistics.  
We will model the impact of stimulus on two timing measures of pharyngeal bolus flow from the 
videofluoroscopy (i.e., a) the interval from the bolus passing the mandibular ramus until laryngeal 
vestibular closure; b) the interval from the bolus passing the mandibular ramus until entering the upper 
esophageal sphincter)  and on measures of post-swallow residue (Normalized Residue Ratio Scale). The 
Saxon test results regarding oral dryness will be used as a covariate for all analyses, as illustrated in the 
Figure below: 
A path analysis approach will be used to first identify differences in tongue pressure across stimuli 

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(Question 1). If confirmed, this potential modulator will be added to the Question 2 model as a covariate 
(Question 3).  The planned analyses will involve linear mixed model repeated measures ANOVAs with a 
factor of stimulus. 
For Aim 3, we will use qualitative methods to describe participant reports of adherence to the 
prescribed thickener.  Information from the quality of life and performance status scales collected in 
session 1 will be used to inform our understanding of variations on patterns of thickener acceptance. 
4. 
Risks and Benefits 
 
Risks  
The following risks will be disclosed to all participants prior to obtaining their consent to participate:  
a) Participants may experience local mucosal irritation from the glue on the adhesive strip used to 
attach the tongue‐pressure bulbs for data collection. The glue usually wears off within 90 minutes 
following the conclusion of data collection. In the incidence that participants are unable to tolerate the 
attachment of the sensors, we will use the IOPI tongue bulbs to collect tongue measurements, and 
collect videofluoroscopic data using the same protocol.  
b) Participants may dislike the taste or texture of some of the thickened liquid stimuli in the study. 
Participants will be reminded that they are free to discontinue participation at any time. 
c) Participants may experience some fatigue during the videofluoroscopy data collection session. 
Participants will be reminded that they should disclose any fatigue or discomfort to the research team, 
and that they are free to discontinue any particular session or to withdraw from the study at any time. 
d) Participants will receive additional exposure to radiation during the videofluoroscopy, in addition to 
their recent radiation treatment protocol.  Based on a previous videofluoroscopic study that we have 
conducted in healthy adults, the study is expected to involve 118+/-18 seconds of radiation exposure 
(Molfenter & Steele, 2013), with an associated dose estimate of <0.35 milliSieverts. Moro and Cazzani 
showed that this dose (0.35mSv) corresponds to a risk of 1 in 39,000 of developing a radiation-induced 
stochastic effect from a videofluoroscopy. We will use a 2-minute warning bell to alert the data 
collection team to exposure time, and will terminate the protocol at the first opportunity following the 
bell. 
e) Aspiration (entry of material into the airway) is a possible risk during the videofluoroscopic 
swallowing study that will be performed. This risk is always present for videofluorscopic swallowing 
studies, which are intended to document the presence and severity of swallowing abnormalities, 
including (but not limited to aspiration). When aspiration is observed, standard procedures will be 
followed to encourage coughing and throat clearing to expel the aspirated material.  The protocol will 
be terminated immediately. Any participant who experiences aspiration will be counseled regarding 
aspiration prevention strategies and aspiration‐risk following the videofluoroscopy. 
f) Choking is an extremely unlikely event.  However, in the event of choking, routine emergency 
procedures will be followed.  All study personnel carry current CPR certification.   

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g) In the unlikely event that an incidental finding is noted on the videofluoroscopy (such as a 
diverticulum or a mass) the attending SRRL licensed speech-language pathologist will consult the on-call 
radiologist and generate a clinical report documenting the observation. These findings will be 
communicated with the participant as per usual clinical practice and follow up with their physician will 
be recommended. 
 
Benefits 
Participants who aspirate during the videofluoroscopy and demonstrate safer swallows using the 
thickened stimuli that are tested will be provided with 2 cans of the thickener-type from which they 
benefitted and instructions for use. Ongoing use of this thickener, as instructed, may reduce their risk 
for subsequent aspiration and related sequelae.  
5. 
Privacy and Confidentiality 
 
Routine practices for ensuring the confidentiality and privacy of all participants will be followed in this 
study. All research personnel at the Toronto Rehabilitation Institute are required to sign a confidentiality 
agreement at the time of hire.  
Participants will be assigned a non-identifying alphanumeric study code, and the master key for this 
code will be retained separately by the PI in a password-protected file on a secure, password-protected, 
encrypted research server. Daily back-up of this research server is performed centrally at the Toronto 
Rehabilitation Institute to protect against data loss. Hard copies of the participant consent forms will be 
maintained in a folder, kept in a locked filing cabinet in the Swallowing Rehabilitation Research Lab.  
All waveform and videofluoroscopic data will be stored electronically on the secure, password 
protected, encrypted research server. Any hard copy data will be transcribed into an electronic file 
(stored on the server), and the hard copy records will be stored in a locked filing cabinet in the 
Swallowing Rehabilitation Research Lab. Only the participant’s alphanumeric study code number will 
appear on the data collection sheets and in the data collection files.  
Access to participant information and experimental raw data will be restricted to the study personnel 
named in this application. All records will be destroyed after 10 years under the supervision of Dr. 
Steele.  
In the event of inappropriate release of personal health information, further release of information will 
be stopped, any information that can be retrieved will be retrieved, the UHN Privacy Office and REB will 
be notified, and any recommended further actions will be taken. 
6. 
Compensation 
 

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Data collection for each participant will involve 3 separate appointments and two post-study follow-up 
telephone call: a) intake; b) Session 1; c) Session 2 (videofluoroscopy); and d) follow-up phone calls at 2 
weeks and 3 months following Session 2. Each face-to-face appointment is expected to last 1 hour.  An 
honorarium of $50 will be provided per participant to cover expenses associated with participation in 
the study. This will be paid at the end of the videofluoroscopy session. Additionally, two cans of 
thickener will be provided to participants for whom thickening is shown to be effective for reducing 
aspiration. 
7. 
Conflicts of Interest 
Dr. Steele, the principal investigator, holds current and prior research contracts with Bracco Canada and 
Nestlé Health Science, who are manufacturers of the barium products and thickening agents that will be 
used in this study.  She has also served in an advisory capacity on expert panels for Nestlé Health 
Science. These relationships will be disclosed to participants in the study information sheet. All products 
for use in the study will be purchased.  Neither Bracco Canada nor Nestlé Health Science will have any 
role as sponsors of this study.  Dr. Steele will not receive any financial payment, either personally or to 
the lab, related to the use of Nestlé or Bracco products in this study. Carly Barbon receives a stipend 
from the University of Toronto.  
8. 
Informed Consent Process 
All participants who show an interest in participating will be provided with detailed information about 
this study via the Participant Information Sheet and Consent Form two weeks prior to the scheduled 
intake appointment. Only after confirming they have understood all the information that is provided and 
after verifying they have no more questions, can they sign the consent form. A copy of the consent form 
will be provided to them. When the ability to comprehend the study is in question we will also request 
assent from the patient’s substitute decision maker prior to enrolling a patient in the study. 
The consent form includes a specific section requesting consent to use of study-related images for 
future educational and teaching purposes. 
9. 
Scholarly Review 
This parent grant of which this project is a subproject has undergone scientific review by the MFSR Study 
Section of the National Institutes of Health (USA).   
10. 
Additional Ethics Reviews 
There are no additional ethics reviews planned.  

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11. Contracts 
There are no contracts required for this project, which will be conducted exclusively at the Toronto 
Rehabilitation Institute.   
12. Budget 
All costs for this study will be covered by the grant received from the National Institutes of Health.