Study Design
A multi-center, assessor-blinded randomized crossover clinical trial (ClinicalTrials.gov identifier NCT03969095, Registered 31 May 2019; https://clinicaltrials.gov/ct2/show/NCT03969095?term = NCT03969095&rank = 1) titled Tongue Pressure Resistance Training for Swallowing Impairment Post-Stroke (TPRT-SIPS) is being conducted over 3 years at the University Health Network–Toronto Rehabilitation Institute–University Centre in Toronto, Ontario, Canada and Northwestern Medicine—Marianjoy Hospital in Wheaton, Illinois, USA. These sites each have stroke programs that provide inpatient and outpatient services.
Informed consent is obtained from each participant prior to enrollment in the study. Once obtained, participants are assigned a unique study participant number used on all documentation. Three trials of maximum isometric tongue pressures are collected at the anterior location from each participant. Eligibility to proceed to the next part of the study is achieved if they display decreased tongue pressures measured using the Iowa Oral Performance Instrument (IOPI) as compared to healthy normal individuals (<40 kilopascals) on all three trials. A VFSS is then completed to confirm impaired swallowing safety and therefore, eligibility for study inclusion.
Participants are enrolled and receive a computer generated randomization number if a PAS score of 3 or above is observed by a study member on any of the 8 swallowing trials in the baseline VFSS assessment. All participants complete a baseline VFSS, 4-week course of tongue-pressure resistance training followed by a VFSS, and a 4-week no-treatment/detraining phase followed by a VFSS regardless of allocation, see Table 1.
Table 1.
Schedule of enrollment, interventions, and assessments
|
|
STUDY PERIOD
|
|
Enrollment
|
Baseline
|
Allocation
|
Post-allocation (Weeks)
|
Close-out
|
TIMEPOINT
|
– 12 to 0 Weeks
|
– t0
|
0
|
1
|
2
|
3
|
4
|
Midpoint
|
5
|
6
|
7
|
8
|
Final
|
ENROLLMENT:
|
|
Informed consent
|
X
|
|
|
|
|
|
|
|
|
|
|
|
|
Eligibility screen
|
X
|
|
|
|
|
|
|
|
|
|
|
|
|
Allocation
|
|
|
X
|
|
|
|
|
|
|
|
|
|
|
INTERVENTIONS:
|
Group 1 (delayed)
|
|
|
|
|
|
|
|
|
X
|
X
|
X
|
X
|
Exit at week 8
|
Group 2 (immediate)
|
|
|
|
X
|
X
|
X
|
X
|
|
|
|
|
|
Exit at week 8
|
ASSESSMENTS:
|
VFSS
|
|
X
|
|
|
|
|
|
X
|
|
|
|
|
X
|
Tongue Pressures
|
|
X
|
|
|
|
|
|
X
|
|
|
|
|
X
|
IDDSI-FDS
|
|
X
|
|
|
|
|
|
X
|
|
|
|
|
X
|
Participant timeline according to the SPIRIT Statement [14]
VFSS Videofluoroscopy, IDDSI-FDS: International Dysphagia Diet Standardisation Initiative.
|
We propose the enrollment of a study sample of approximately 40 participants. Participants will be allocated either to a delayed treatment group involving a 4-week waiting period prior to beginning the 4-week training or to an immediate treatment group (followed by a 4-week post-treatment detraining phase). The allocation sequence for randomization numbers is stored in password protected files at the primary study site where the lab manager is the only individual with access to this concealed sequence until interventions are to be assigned. Once safety concerns are identified on baseline assessment, study members reach out to the lab manager to assign the participant and allocation to either group in the trial. The sample size calculation for this study was based on 2-sided chi-square testing for association between treatment group (Immediate and Delayed) and swallowing safety (Safe vs. Unsafe). A study with a power calculation of 0.8, and standard deviation of proportion of unsafe swallows set at 0.5 will require a sample size of 32 participants (n = 16 per group) to test the association at a 0.05 significance level. The power calculation was carried out using Study Size 3.0. We will enroll a total of 40 participants (n = 20 per group) to account for participant attrition. The use of a crossover design will allow for the evaluation of outcomes at different stroke time points and attaining the required level of statistical power, along with the quantification of swallow recovery with and without treatment exposure. Each participant will serve as their own control, while allowing for an exploration of treatment effects and their interaction with neuronal recovery periods for statistical analyses.
Participants
All participants are approached by a member of their circle of care who introduces the study. Screening for inclusion is completed through review of both the paper chart and the electronic medical record. Participants then meet with a member of the research team who reviews study procedures and obtains informed consent from each participant. Inclusion and exclusion criterial are detailed in Table 2.
Table 2.
Trial Inclusion and Exclusion Criteria
|
Inclusion Criteria
|
Exclusion Criteria
|
1. ≥ 18 years old
2. Stroke type: ischemic stroke (first-ever)
3. Stroke region: Supra-tentorial
4. Time-point: Within 3 months of stroke
5. Diagnosis confirmed via neuroimaging techniques (computed tomography or magnetic resonance imaging)
6. Decreased tongue pressures on IOPI
7. Pharyngeal dysphagia (safety concern operationalized as a score of 3 or more on the penetration-aspiration scale)
|
1. History of head and neck cancer
2. Radical neck dissection (e.g. anterior cervical surgery fusions) or neck/ oropharyngeal surgery (not excluded – tonsillectomy, adenoidectomy, tracheostomy)
3. Past medical history of any neurological disease other than stroke (e.g. MS, PD, ALS, TBI)
4. Oral apraxia, impairing the participant’s ability to complete exercises
5. Cognitive or receptive communication difficulties that preclude the participant’s ability to follow study instructions
4. Allergies to barium, potato starch, corn starch, xanthan gum, milk products, or latex
|
Standardized VFSS protocol
Each participant will complete instrumental videofluoroscopic swallowing studies at three time-points in the study based on their group allocation. These studies will utilize a pulse rate of 30 pulses per second to generate 30 images per second, which will be recorded using a properly synchronized recording system (either the KayPentax Digital Swallow Workstation or the TIMS DICOM System) at 30 frames per second. The VFSS protocol involves up to four natural cup sips of Level 0 thin liquid stimuli and up to four natural cup sips of Level 2 mildly thick liquid stimuli as defined by the International Dysphagia Diet Standardisation Initiative (www.iddsi.org). All liquids are mixed with barium sulfate in a 20% weight-to-volume concentration using either Bracco E-Z-Paque® or Varibar® Thin Liquid powdered barium. The mildly thick liquids are prepared using a xanthan gum based thickening agent (Nestlé Resource® ThickenUp® Clear). Participants are provided with cups containing 40 milliliters of liquid for each sip, and cups are weighed pre and post administration to calculate the total volume of liquids swallowed per sip. Of the four mildly thick liquid trials, two are completed with the IOPI bulb positioned anteriorly (directly behind the upper incisors) in order to collect tongue pressures during swallowing. The VFSS protocol is outlined in Figure 2.
Insert Figure 2 about here
In order to ensure that participants are not exposed to harm through participation in the study, a number of discontinuation rules will be employed during each VFSS:
- If aspiration of liquid (Penetration-Aspiration Scale of 6 or more) is observed during the study for a certain consistency, that consistency or method of administration (e.g., with IOPI in mouth) will no longer be offered to the participant.
- When three instances of aspiration have been observed in total, the VFSS exam will be terminated.
- If the vallecular or pyriform sinus spaces are overflowing with residue with potential danger of entry into the airway, participants will be cued to swallow a second time to clear the residue. If this is ineffective, that method of administration will no longer be offered to the participant.
- If the duration of radiation exposure exceeds 3.5 minutes in total, the VFSS will be concluded.
Training Program:
The training protocol consists of a total of 8 intervention sessions completed twice per week over the span of four weeks. Study participants are asked from completion the following exercises during the trial: effortful swallows, Shaker exercise, Mendelsohn maneuver, Masako Maneuver, jaw opening against resistance, and chin tuck against resistance as they may interfere with trial results. Each session will be supervised by an S-LP and require a maximum of an hour in length. The program is designed to utilize a combination of strengthening tasks alongside swallowing tasks using biofeedback in order to optimize generalization to real-life swallowing conditions. Sessions completed with the S-LPs will be comprised of the following:
- 20 repetitions of maximum isometric presses (MIPs) emphasizing rapid generation of pressure (“rapid rise”) at the anterior palate bulb location. A mark will be made by the S-LP on the connecting tube of the bulb at the level of the incisors at the beginning of the session to ensure accurate and consistent placement of the bulb during practice.
- 15 regular saliva swallows with the IOPI bulb in place. The mark on the connecting tube will be aligned with the upper incisors. A mandatory rest period of 30 seconds will be utilized per saliva swallow.
- 15 effortful saliva swallows with the IOPI bulb in place. The mark on the connecting tube will be aligned with the upper incisors. A mandatory rest period of 30 seconds will be utilized per saliva swallow.
- 10 generalization tasks with the IOPI in place along with a mildly thick liquid sip. The mark on the connecting tube will be aligned with the upper incisors, then one natural cup sip of mildly thick liquid will be provided for each swallow.
Additionally a home practice component using IOPI bulbs with a target of 30 additional repetitions daily of the MIP and the Saliva Swallow tasks is included. Participants will be provided with a daily homework log to document practice, and will review this log weekly with their S-LP.
A participant will be withdrawn from the study if they miss a total of 3 consecutive intervention sessions under the direct supervision of an SL-P, or develop a new health concern.
Outcome measures:
Tongue pressures using the IOPI device using different tasks repeated three times each will be collected at each encounter during the study. Maximum isometric tongue pressures will be collected at the (1) anterior location where the tongue bulb will be positioned behind the upper incisors and the participant will be instructed to squeeze the bulb hard; and (2) posterior location lining the tongue bulb with the molar teeth with similar instruction to squeeze the bulb hard. Regular effort saliva swallow pressures will also be collected, where the tongue bulb is again lined up behind the upper incisors and participants are instructed to swallow their saliva with normal effort, allowing at least 30 seconds between trials.
International Dysphagia Diet Standardisation Initiative Functional Diet Scale (IDDSI-FDS) scores will be collected at each encounter to monitor the degree of diet texture modification used and the time-points at which any changes in diet texture occur relative to the treatment program.
Videofluoroscopic swallowing measures will be collected at baseline, post 4-week waiting/detraining period, and post 4-week treatment for each group using a standardized videofluoroscopy protocol. VFSS recordings are de-identified, spliced into separate clips for each bolus, and arranged in a randomized order for duplicate rating. Rating is completed at the Toronto Rehabilitation Institute site by two S-LPs at the Swallowing Rehabilitation Research Laboratory (SRRL) trained using the ASPEKT method [13] and blinded to participant and VFSS time point for the following parameters:
- Penetration-Aspiration Scale (PAS)
- Pixel-based measures of post-swallow residue
- Swallow Reaction Time
- Time–to–Laryngeal Vestibule Closure
- Laryngeal Vestibule Closure Duration
- Hyoid burst kinematics (Hyoid velocity and peak position)
- Pharyngeal Area at Rest
- Pharyngeal Area at Maximal Pharyngeal Constriction
The primary outcome of interest is swallowing safety as measured using the penetration-aspiration scale.
Confidentiality
All participant data will be coded using an alphanumeric study code. The master key linking the study code to patient identity will be maintained at the University Health Network—Toronto Rehabilitation Institute—University Centre, and by the lead investigators at Northwestern Medicine—Marianjoy Hospital. Personnel involved in the study (recruitment, consent, and completing the intervention) will have direct access to the study related documents. VFSS studies will be de-identified and stored electronically on a secure, password-protected, encrypted research drive at the University Health Network—Toronto Rehabilitation Institute—University Centre. Any data collected on paper will be inputted into electronic documents and shredded.
VFSS data and scanned copies of paper study forms from the Northwestern Medicine—Marianjoy Hospital site will be transferred to the University Health Network—Toronto Rehabilitation Institute—University Centre using OneDrive. As patient VFSS studies are considered personal health information and are protected under the Personal Health Information Protection Act (PHIPA), they will be archived at the end of the study and stored at University Health Network—Toronto Rehabilitation Institute—University Centre for a period of 10 years after which they will be disposed of in a secure manner.
Statistical analysis
Excel software will be used for data extraction and IBM SPSS Statistics will be used for statistical analysis. Swallowing safety and efficiency measures will be transformed to binary measures (e.g. safe/unsafe; efficient/inefficient) in order to facilitate comparisons. As we are dealing with categorical variables as our primary exposure and outcome variables, a binary logistic regression model will be used to explore the association, if any, between the treatment groups and the transformed swallow safety measures. Other possible variables that have been identified by the literature to possibly influence this association will be taken into account and included in the model (covariates: of time-since-stroke, time-point; modifier: stroke severity; stroke location).
For continuous measures of swallowing physiology, parametric analyses, such as repeated measures ANOVAs, will be used to detect overall differences between related means across different conditions (bolus types) and time points (pre-post intervention).