Neoplasms

All Conditions

Digestive System Diseases

Ear, Nose, and Throat Diseases

Mouth and Tooth Diseases

Carcinoma

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Deglutition Disorders

Esophageal Diseases

Gastrointestinal Diseases

Pharyngeal Diseases

Otorhinolaryngologic Diseases

Participants will be trained to initiate swallowing during expiration.

Participants will practice swallowing, but will not learn the key therapeutic element (i.e., initiating swallowing during expiration).

Participants will complete 6 respiratory-swallow phase training sessions that will last approximately one hour.

Respiratory-Swallow Phase Training

Participants will complete 6 "swallow practice" sessions that will last approximately one hour.

Swallow Practice

Bonnie Martin-Harris, PhD

Head and neck cancers have escalated to epidemic levels in the United States, and survivors are suffering from life-long, devastating swallowing disorders with limited therapeutic options. This clinical trial investigates a novel swallowing treatment that trains initiation of swallowing during the expiratory phase of respiration to improve swallowing safety and efficiency.

Head and neck cancers (HNC) have increased to epidemic levels in the United States. Despite good response to cancer treatment, survivors are suffering life-long toxicities that result in swallowing problems (dysphagia). Treatment options for dysphagia after HNC are extremely limited, focus on swallowing movements alone, and do not consider the importance of respiratory-swallow phase patterning. Prior evidence has demonstrated that when aberrant respiratory-swallow phase patterning is present (initiation of swallowing during inspiration) in patients with HNC, there is a higher occurrence of swallowing impairments, increased residue, and airway invasion. Further, it has been well established that the expiratory limb of the respiratory cycle provides a biomechanically advantageous set point in which to initiate safe and efficient swallowing. This randomized, controlled, Phase II clinical trial examines if respiratory-swallow phase training improves airway protection and swallowing efficiency in HNC survivors who are three or more months post-completion of first-line cancer treatment. The primary goal (Aim 1) is to determine if respiratory-swallow phase training results in increased frequency (%) of swallows initiated during expiration and improved swallowing safety. The secondary goal (Aim 2) is to examine the impact of respiratory-swallow phase training on the frequency of swallows initiated during expiration in wakeful, naturalistic swallowing environments, including eating and drinking. The investigators will recruit 88 HNC survivors with dysphagia, impaired respiratory-swallow phase patterning, and airway compromise. The investigators will deliver therapy remotely using a telehealth platform and an innovative wearable sensor that provides real-time visual feedback of respiratory-swallow movements. Endpoints will be measured from synchronized videofluoroscopic and respiratory-swallow sensor recordings at baseline, within 1-week post-treatment, and 1-month and 3-months post-treatment.

Participants and outcome assessors will be naive to experimental condition.

Training Swallowing Initiation During Expiration

Training Swallowing Initiation During Expiration: Impact on Safety and Efficiency Following Treatment for Oropharyngeal Head and Neck Cancer

Evaluates the impact of dysphagia on the quality of life of patients with head and neck cancer

Determines percent (frequency) of the target (expiratory phase) for each swallow.

Measures presence, depth and reaction to penetration and aspiration.

Quantifies pharyngeal space residue obtained in the lateral view during Modified Barium Swallow Study (MBSS)

Measures physiologic swallowing impairment from observations of MBSS recordings

Northwestern Memorial Hospital

Northwestern University

Professor

Oropharyngeal Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Stomatognathic Diseases

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Pembrolizumab

Antibodies

Antibodies, Monoclonal

Cetuximab

Cisplatin

Immunomodulating Agents

Durvalumab

Immunoglobulins

Mitogens

Antibodies, Blocking

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients treated with definitive RT and chemotherapy (cisplatin) or targeted therapy (cetuximab)

Patients treated with definitive RT and immunotherapy (pembrolizumab, nivolumab, or durvalumab)

Routine radiation dosing (approximately 70 Gy in 35 fractions over 6.5 weeks) to the head and neck for the treatment of head and neck cancer

Radiation Therapy

Cetuximab is an epidermal growth factor receptor (EGFR) inhibitor used for the treatment of head and neck cancer

Cisplatin is a chemotherapy medication used to treat a number of cancers, including head and neck cancer

Chemotherapy

Keytruda or Pembrolizumab is a highly selective humanized monoclonal IgG4 antibody directed against the PD-1 receptor on the cell surface.

Opdivo or Nivolumab is a targeted therapy. It is a human programmed death receptor-1 (PD-1) blocking antibody.

Imfinzi or Durvalumab is an anti-cancer ("antineoplastic") drug. This medication is classified as an Anti-PD-L1 monoclonal antibody.

Immunotherapy

Khusbu Singh, MBBS, CCRP

Gerald Henderson

Khushbu Singh, MBBS, CCRP

Loren Mell, MD

Gerald Henderson, BA

Loren K Mell, MD

To use novel methods for quantitative analysis of VFSS (videofluoroscopic swallow study, also known as modified barium swallow) to study and compare dysphagia in patients treated for head and neck carcinoma with concurrent radiation therapy and chemotherapy (cisplatin) or targeted therapy (cetuximab) vs. immunotherapy (pembrolizumab, nivolumab, or durvalumab).

Our hypothesis is that pharyngeal constriction will be greater (lower ratio) with concurrent immunotherapy compared to chemotherapy, as measured by the pharyngeal constriction ratio (PCR).

The QUASAR study will use a prospective, observational, cross sectional design (See Schema). HNC patients treated with definitive RT and immunotherapy or chemotherapy (cetuximab or cisplatin) will undergo VFSS at 4-6 and 12-24 months post-treatment. Patients enrolled prior to 6 months after finishing therapy will undergo a swallow study during the 4-6 month period AND the 12-24 month period. Patients enrolled after 6 months after finishing therapy will undergo a single swallow study in the 12-24 month period. The primary endpoint of PCR at 12-24 months will be compared between patients treated with immunotherapy versus chemotherapy.

All patients with HNC treated with definitive RT and systemic therapy at our institution will be eligible. In particular, we will recruit patients for this study from participants in two ongoing trials investigating the use of concurrent immunotherapy. The KEYCHAIN trial (ClinicalTrials.gov Identifier: NCT03383094) randomizes patients with locally advanced p16+ HNC undergoing definitive RT to concurrent q3 week cisplatin versus concurrent and adjuvant pembrolizumab. NRG-HN004 (ClinicalTrials.gov Identifier: NCT03258554) is a cooperative group trial that compares HNC patients that are not eligible for cisplatin undergoing definitive radiation therapy to concurrent cetuximab versus durvalumab.

QUantitative Assessment of Swallowing After Radiation (QUASAR)

QUantitative Assessment of Swallowing After Radiation (QUASAR): A Longitudinal Comparison of Swallowing Function by Systemic Therapy in Head and Neck Cancer Patients

will use a two-sample t-test at 0.05 level to compare Pharyngeal Constriction Ratio (PCR) between groups

To compare swallowing function between systemic therapies with additional quantitative metrics of swallowing dysfunction from the VFSS including TPT, PRR and PPWT.

The presence of aspiration or strictures on VFSS will be compared as binary variables between groups using Pearson's Chi squared test.

To compare patient reported assessments of swallowing function with the EAT-10 tool between systemic therapies.

To test if there is correlation between the quantitative VFSS metrics and patient reported outcomes on the EAT-10 index, we will calculate Pearson's correlation coefficient and plot the results on a correlation matrix. The Holm step down procedure will be used to adjust for multiple testing to control the family-wise error rate at 0.05 level.

The purpose of this aim is to evaluate the effect of radiation dose on swallowing structures, applying a previously developed space-preserving NTCP approach based on principal component analysis (PCA).

Using this approach, dose distributions to the global swallowing apparatus (i.e. pharynx, larynx and esophagus) will be standardized for patients from both arms of Aim 1, using deformable registration to standardize organs and 3-D dose distributions to a common template. Dose distributions will be converted into a dose array and PCA will be applied to the dose array, as previously described. We will then use PC linear regression to identify eigenvectors significantly associated with long term dysphagia (as measured by PCR).

Director, Division of Clinical and Translational Research/ Department of Radiation Medicine and Applied Sciences

Control (Usual care) group in which patients will receive swallowing and prescribed dietary intervention during the radiotherapy period prescribed by the attending physician.

Patients receive twice daily swallowing intervention by a speech language pathologist, consisting of the battery of isometric / isotonic exercises.

Patients will receive a one time only swallowing intervention session by a speech language pathologist, instructing them in the battery of isometric / isotonic exercises plus a home practice instruction digital video tape to support self directed practice of this program at home.

swallowing intervention by a speech language pathologist, consisting of the battery of isometric / isotonic exercises

Pharyngocise

Giselle Carnaby-Mann, PhD

In this study supported by an American Cancer Society grant, the investigators are evaluating two levels of swallowing exercise intensity on the maintenance of swallowing muscles and their function in Head/Neck cancer patients undergoing radiotherapy. Patients in this study are randomly placed into different exercise groups and provided with exercises to perform daily during their radiation treatment. Their progress, diet management and swallowing ability are monitored throughout the treatment period and followed up until 3 months after radiation treatment. In addition to the daily treatment details, the patients perception of their swallowing ability and concerns about their health and treatment are also measured. This clinical trial will help to refine a previously investigated simple exercise package and provide a program of intervention that can help prevent medically related complications of swallowing difficulty (e.g. pneumonia, dehydration, prolonged tube feeding), and improve the ability to eat for patients with head / neck cancer. Ultimately it is hoped that this form of exercise therapy will help reduce the costs (personal and financial) to the patient, caregivers and community.

In an earlier pilot study, a regime of simple swallowing exercises was identified as useful in maintaining oropharyngeal muscle characteristics as measured by T2 weighted Magnetic Resonance Imaging (MRI) and produced a trend toward improved function for swallowing in patients undergoing radiotherapy for head and neck cancer. The purpose of this current study is to evaluate the dose response of two levels of swallowing exercise intensity on the maintenance of muscle composition and function for swallowing in Head/Neck cancer patients undergoing radiotherapy.

HYPOTHESIS: A program of intensive swallowing exercise (Pharyngocise) will maintain muscle function in the oral cavity and pharynx during radiotherapy, preserving or supporting swallowing function in Head/Neck cancer patients.

STUDY DESIGN: 130 patients with Head/Neck cancer, confirmed by clinical history and exam, will be recruited over a 4 year period. All subjects will undergo an initial baseline work up, including a standardized clinical and instrumental swallowing evaluation, psychosocial scales, nutritional exam, and T2 weighted MRI prior to the first radiation therapy. Subjects will be randomized into 1 of 3 groups:

Group A: Usual care (control) group - patients will receive swallowing and prescribed dietary intervention during the radiotherapy period prescribed by the attending physician.

Group B: High intensity pharyngocise treatment group - patients will receive twice daily swallowing intervention by a speech language pathologist, consisting of the battery of isometric/isotonic exercises.

Group C: Low intensity pharyngocise treatment group - patients will receive a single instructional exercise session on the isometric/isotonic exercises from a Speech Language Pathologist and a practice tape to support home practice of the exercises.

All patients will be treated for approximately 6 weeks and followed for 3 months post treatment. Baseline assessments will be repeated. In addition, daily treatment details, patients perception of current swallowing ability and progress in therapy will be recorded by the Speech Pathologist. Participants will be independently monitored throughout the treatment period by researcher blind to the treatment group assigned, via weekly phone interview sessions. Compliance with the treatment techniques, and the occurrence of any negative endpoints such as occurrence of aspiration pneumonia will be recorded.

Pharyngocise Dose Response Study

Muscle Preservation and Swallow Function Following Radiotherapy: A Dose Response Study

T2 Weighted Magnetic Resonance Imaging (MRI) to quantify baseline muscle parameters in the oral cavity and pharynx. The regions of interest will be identified on images using axial and coronal planes. Information regarding the muscle volume, composition (fat Vs muscle Vs edema) as reflected by the signal intensity.

Swallowing ability and method/ type of dietary intake, e.g. Functional Oral Intake Scale score \[F.O.I.S\] over the study period

Weight and Body Mass Index will be calculated.

Domain assessments for, quality of life, pain,and fatigue using the Functional Assessment of Cancer Therapy - Head and Neck (FACT-H/N), Pain Disability Index (PDI), Functional Assessment of Cancer Therapy - Anemia (FACT-An) scale, Multidimensional Fatigue Symptom Inventory (MFSI), Profiles of Mood Scale (POMS) and Center for Epidemiologic Studies Depression Scale(CESD).

Range of swallowing biomechanics measured from endoscopic and fluorographic evaluations.

Patient perception of effect of swallowing disability - Swallowing Quality of Life (SWAL QOL) score during the study period.

American Cancer Society, Inc.

University of Florida

31 subjects will be receiving two doses of 150 x 10⁶ AMDC-GIR spaced 4-6 weeks apart.

31 subjects will be receiving two doses of identical placebo composed of the same cryopreservation medium used for AMDC-GIR. Doses will be spaced 4-6 weeks apart.

The study will treat 62 patients at 2 clinical sites: UC Davis Center for Voice and Swallowing and UCSF Voice and Swallowing Center. Patients will be randomized 1:1 to receive either 2 AMDC-GIR doses of 150 x 10⁶ cells or 2 doses of identical placebo composed of the same cryopreservation medium used for AMDC-GIR. Enrollment is expected to be completed within 2 years of initiating the study. Patients will be followed for 24 months post-treatment.

Autologous Muscle Derived Cells for Gastro-Intestinal Repair (AMDC-GIR)

two doses of placebo will be administered and spaced 4-6 weeks apart.

Placebo

Johnathon D Anderson, PhD

Randev S Sandhu, BS

Peter Belafsky, MD

Maggie Kuhn, MD

Daniel Cates, MD

James Lappin, BA

Claire Perrin, BS

Clark Rosen, MD

Yue Ma, MD

The primary objective of this double-blind, randomized, placebo-controlled, multicenter clinical trial is to evaluate the safety of AMDC-GIR during the 24 months following 2 consecutive treatments of tongue dysphagia in male and female patients who have undergone surgery and/or chemo- and/or radiotherapy for squamous cell cancer of the oropharynx.

The purpose of this double-blind, randomized, placebo-controlled, multicenter clinical trial is to evaluate the safety and efficacy of Autologous Muscle Derived Cells for Gastro-Intestinal Repair (AMDC-GIR) for the treatment of tongue dysphagia (TD) in male and female patients who have undergone surgery and/or chemo- and/or radiotherapy for squamous cell cancer of the oropharynx.

Surgery, chemo- and radiotherapy induce significant TD and result in long-term swallowing dysfunction. The incidence of TD after treatment for cancer of the pharynx exceeds 80%. Therefore, augmenting tongue muscle function may be beneficial to patients. Autologous muscle cell therapy, which involves isolation of cells from skeletal muscle biopsies, ex vivo expansion, and subsequent injection into the tongue, may serve as a durable therapy. In animal studies, muscle derived cells have successfully integrated within tissue to improve tongue strength and function. Intramuscular injection of AMDC-GIR has been shown to produce localized tissue changes at the injection site without a systemic effect. Initial results of a Phase 1 open label trial suggest that 150 x 10⁶ AMDC-GIR for the treatment of TD is safe and may be efficacious. A Phase I/II placebo controlled, randomized clinical trial is warranted.

Patients will receive two treatments of intramuscular injection of 1 AMDC-GIR dose of 150 x 10⁶ cells or identical placebo. For entrance into the study, patients must meet the study inclusion criterion and must not meet any of the exclusion criteria. Patients will have quantitative and qualitative measures of swallowing impairment assessed before treatment and at prescheduled intervals after treatment.

The study will treat 62 patients at 2 clinical sites: UC Davis Center for Voice and Swallowing and UCSF Voice and Swallowing Center. Patients will be randomized 1:1 to receive either 2 AMDC-GIR doses of 150 x 10⁶ cells or 2 doses of identical placebo composed of the same cryopreservation medium used for AMDC-GIR. Enrollment is expected to be completed within 2 years of initiating the study. Patients will be followed for 24 months post-treatment.

Male and female patients at least 18 years of age who have undergone surgery and/or chemo- and/or radiotherapy for primary treatment of oropharyngeal squamous cell cancer and who present with symptoms and findings of TD will be eligible for participation. Eligible patients will have muscle tissue harvested using an established needle biopsy technique during an outpatient procedure.

The harvested muscle will be placed in a hypothermic medium and transported to the manufacturer for cell processing. The muscle derived cells (MDC) will be isolated and expanded in culture over several weeks to a final AMDC-GIR dose of 150 x 10⁶ cells. Each patient will receive 2 doses of cells or placebo spaced 4-6 weeks apart.

After reaching the desired concentration, the isolated and expanded AMDC-GIR or identical placebo will be frozen and shipped back to the investigating physician. The investigative team will thaw the AMDC-GIR and dilute the sample with an equal volume of physiological saline. Under direct vision, the resulting suspension will be injected into the patient's tongue in a brief outpatient procedure for the patients randomized to the treatment arm. Patients randomized to receive placebo will undergo an identical procedure utilizing a thawed solution of frozen media without cells. Both patient and clinician will be blind to the treatment and placebo status.

Patients will be assessed for improvement in TD at 6 months, 12 months and 18 months and 24 months following treatment. Adverse events will be assessed at those visits, as well as during virtual visits at 1-2 days, 1 week, 4 weeks, 3 months, 15 months, 21 months and 24 months. Adverse events will also be assessed at 6 months post-injection in patients who were in the placebo group and elected to receive AMDC_GIR injections after the unblinding. Patient reported outcome measures will be assessed at 4 weeks, 3 months, 6 months, 12 months, 18 months and 24 months.

Double-blind, randomized, placebo-controlled, multicenter clinical trial

Patients will receive two treatments of intramuscular injection of 1 AMDC-GIR dose of 150 x 10⁶ cells or identical placebo. Both patients and study investigators at all sites will be blinded to the treatment assignment of patients.

Autologous Muscle Derived Cells for Treatment of Tongue Dysphagia

A Multi-Center, Double-Blind, Randomized Placebo-Controlled Investigation of Autologous Muscle Derived Cells (AMDC) for the Treatment of Tongue Dysphagia Resulting From the Treatment of Head and Neck Cancer

Efficacy of AMDC-GIR in the improvement of objective fluoroscopic swallowing parameters

Effects of AMDC-GIR on patient reported smell and taste as reported by the 8-question survey ChemoSensory Questionnaire (CCQ). Minimum score for each scale, 4 Maximum score for each scale, 20. High score indicates better function

Effects of AMDC-GIR in the improvement of objective voice quality. The CAPE-V approach uses a form where Overall Severity, Roughness, Breathiness, Strain, Pitch, and Loudness are rated using a 100-mm visual analog scale. The rater places a vertical mark along each horizontal line where the far left end of the line represents the least impaired status and the far right represents the one most impaired. Scores are obtained by making measurements to the nearest millimeter from the left most (least impaired) end of the horizontal line. The higher the score the worse the impairment.

Effects of AMDC-GIR on patient reported quality of life. FACT-HN is a 39-question survey, with a score range from 0-148. The higher the score the better the quality of life for the patient.

Safety will be determined by the frequency and severity of adverse events related to study procedures and study product.

Efficacy of AMDC-GIR in the improvement of objective Anterior Tongue Pressure Measurement (IOPI)

Effects of AMDC-GIR on incidence of patient reported aspiration pneumonia (yes/no scoring criteria)

Effects of AMDC-GIR on incidence of patient reported survival (yes/no scoring criteria)

The 8-point Penetration-Aspiration Scale (scores of 1-8, 1=better, 8=worse, see table below) is the standard method used measure the severity of airway invasion during swallowing.

1. Material does not enter the airway
2. Material enters the airway, remains above the vocal folds, and is ejected from the airway
3. Material enters the airway, remains above the vocal folds, and is not ejected from the airway
4. Material enters the airway, contacts the vocal folds, and is ejected from the airway
5. Material enters the airway, contacts the vocal folds, and is not ejected from the airway
6. Material enters the airway, passes below the vocal folds, and is ejected into the larynx or out of the airway
7. Material enters the airway, passes below the vocal folds, and is not ejected from the trachea despite effort
8. Material enters the airway, passes below the vocal folds, and no effort is made to eject

Efficacy of AMDC-GIR in the improvement of objective manometric swallowing parameters

Survey consisting of 10 questions (see table below), each score on a scale of 0-4, with 0= no problem, 4= severe problem.

922 Belafsky et al. Eating Assessment Tool TABLE 3. EATING ASSESSMENT TOOL (EAT-10) Circle the appropriate response. To what extent are the following scenarios problematic for you?

1. My swallowing problem has caused me to lose weight.
2. My swallowing problem interferes with my ability to go out for meals.
3. Swallowing liquids takes extra effort.
4. Swallowing solids takes extra effort.
5. Swallowing pills takes extra effort.
6. Swallowing is painful.
7. The pleasure of eating is affected by my swallowing.
8. When I swallow food sticks in my throat.
9. I cough when I eat.
10. Swallowing is stressful

California Institute for Regenerative Medicine (CIRM)

Cook MyoSite

University of California, Davis

Respiratory Tract (Lung and Bronchial) Diseases

Symptoms and General Pathology

Respiratory Aspiration

Chronically dysphagic, medically stable patients at least 6 months post treatment for head and neck cancer with non-optimal respiratory-swallowing patterns participated in up to 8 sessions of respiratory phase training to learn an optimal respiratory - swallow phase pattern

Patients were presented with visually guided respiratory feedback to train optimal respiratory-swallow coordination patterns.

Respiratory-Swallow Phase training

Bonnie J Martin-Harris

Cancers of the head and neck require surgical, radiation, and chemotherapy treatments that are intended to cure the disease. These treatments have toxic effects on muscles and structures that are necessary to swallow safely and efficiently. The resulting swallowing problems (dysphagia) often remain chronic for Veterans and interfere with their ability to eat and drink. The cost burden to the VA health system is high. There is an urgent need to develop rehabilitative treatments that lessen these burdens. The proposed research is designed to test a novel swallowing therapy that includes the coordination of breathing with swallowing. Our study will train medically and surgically treated, chronically dysphagic Veterans with histories of oropharyngeal cancer in a novel therapy that involves both swallowing and respiratory systems. If the therapy is found to be effective, the long term goal of the project is to extend the study to a multi-site, clinical trial and test the longstanding effect of this treatment compared to other swallowing therapies on swallowing function, QOL and cost.

Swallowing impairments (dysphagia) represent the highest functional morbidity in veteran patients treated for oropharyngeal cancers with either surgical approaches followed by radiation or with more recent organ-preservation protocols. The nature of the impairments is often resistive to treatment and results in life-long health consequences and high cost burden on the VA health system. Recent preliminary data have linked alterations in the otherwise highly stable respiratory-swallowing phase pattern relationships to the swallowing impairment and penetration/aspiration and in this patient group. The immediate goal of this clinical trial is to test the effect of a novel respiratory-swallow intervention on swallowing impairment and penetration/aspiration in a cohort of chronically dysphagic veterans following treatment for oropharyngeal cancer. Patients presenting with a "non-optimal" respiratory-swallow phase pattern during liquid swallows and measurable swallowing impairment will learn an "optimal" physiologic pattern that facilitates both airway protective and mechanical advantages during swallowing. The broad goal of this research is to develop ideal respiratory-swallowing phase training methods and regimens that alone or combined with traditional swallowing treatments improve swallowing function in the acute phases of recovery and improve long term patient outcome. Our intention is to use these preliminary data to motivate a larger clinical trial to compare the effect of respiratory-swallow phase training with other evidenced based methods of swallowing treatment and expand the approach to other patient groups that have indications of respiratory-swallow phase impairments (e.g. pulmonary disease and stroke) contributing to impaired swallowing function

Respiratory-Swallow Training in Veterans With Oropharyngeal Cancer

Respiratory swallow patterns were collected using nasal airflow and respiratory inductance plethysmography (RIP) of each swallow during the modified barium swallow study. The movements of the ribcage and abdomen were recorded using RIP; data synchronized and recorded using the KayPentax Digital Swallow Workstation Signals Lab. Subjects were categorized as optimal (expiratory-expiratory) versus non-optimal (non-expiratory-expiratory).

Analysis of the percentage of impaired swallow components using a dichotomized MBSImP scoring system

The penetration aspiration scale is a validated 8 point interval scale used to describe penetration and aspiration events. Scores are determined primarily by the depth to which material passes in the airway and by whether or not material entering the airway is expelled. Scores \< 3 are considered to be normal. For the purpose of our study scores were dichotimized to normal and impaired.

US Department of Veterans Affairs

Patient completed daily EXACT-PRO questionnaires regarding respiratory symptoms. Reported changes were reviewed by pulmonologist

Chronically dysphagic, medically stable patients at least 6 months post treatment for head and neck cancer with non-optimal respiratory-swallowing patterns

Respiratory-Swallow Phase training: Will present patients with visually guided, respiratory feedback and train optimal respiratory-swallow coordination patterns, thereby providing the airway protection and mechanical benefits that have been observed in healthy individuals.

Arm 1

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Bonnie Martin Harris

Lip closure

Tongue control

Bolus transport

Oral residue

Initiation of pharyngeal swallow

Soft palate elevation

laryngeal elevation

Anterior hyiod excursion

Epiglottic inversion

Laryngeal vestibular closure

Pharyngeal stripping wave

Pharyngoesophageal segment opening

Tongue base retraction

Pharyngeal residue

Pre-intervention

Subjects that completed treatment were assessed within one week of meeting respiratory-swallow phase training goals

One Week Post Intervention

VAMC participants were assessed at one month following completion of the treatment protocol

One Month Post Intervention

Percentage of Impairment According to the Modified Barium Swallow Impairment Profile (MBSImP)

Percentage of Impairment According to the Penetration-Aspiration Scale

One Week Post-intervention

VAMC participants were reassessed at one month post treatment

Optimal Respiratory - Swallow Phase

Chronically dysphagic, medically stable patients at least 6 months post treatment for head and neck cancer with non-optimal respiratory-swallowing patterns

Respiratory - Swallow Phase Training

Overall Study

Nervous System Diseases

Heart and Blood Diseases

Stroke

A Vibrotactile stimulation device will be evaluated in patients with chronic moderate to severe dysphagia for more than 6 months post onset due to stroke or following radiation treatment for head and neck cancer to assess which frequency, mode, pressure characteristics are most helpful in increasing the rate of swallowing, increasing the urge to swallow, assisting with the initiation of swallowing and not affecting discomfort.

Comparison of the effects of different vibratory characteristics on the frequency of swallowing, time of initiation of swallowing with stimulation and urge to swallow. Will compare frequency of vibration, mode of vibration, pressure of device against neck, and duration of vibration. Each session will last no more than 1 hour with short breaks. Each participant can volunteer for up to three nonconsecutive sessions.

Vibrotactile stimulation

Christy L Ludlow, PhD

This is a device evaluation study to determine the optimal stimulation characteristics for using vibrotactile stimulation as a sensory triggering device for self retraining in patients with chronic moderate to severe dysphagia. Stimulation characteristics to be tested are frequency of vibration, pressure between the device and the skin, mode of vibration (pulsed or continuous).

Participants were recruited who had chronic moderate to severe dysphagia following stroke or radiation treatment for head and neck cancer. Their frequency of swallowing was transduced with an accelerometer placed on the skin over the thyroid cartilage and inductive plethysmography bands placed over the rib cage and abdomen. When laryngeal elevation coincided with respiratory apnea a swallow was marked. Five different motor frequencies were evaluated to determine their effect on participants frequency of swallowing (swallows per minute). Frequencies were 30, 70, 110, and 150 Hz and a combination of 70 and 110 Hz. For each vibratory frequency the number of swallows per minute occurring during stimulation was compared with sham when the participant was wearing the device but the motor was not turned on. The frequency fo swallowing during stimulation was compared with the frequency of swallowing between stimulations. Visual analogue ratings of the urge to swallow and discomfort were also measured after each condition. Other parameters were the pressure between the motor and the skin (0, 2, 4, and 6 kPa) and swallow initiation time when stimulation was on and when it was not. Swallowing frequency with continuous versus pulsed stimulation was also compared.

The Passy Muir Swallowing Self Training Device

Passy-Muir Swallowing Self Training Device to Enhance Recovery Post Stroke

Change in number of swallows per minute during stimulation minus swallows per minute during sham (wearing the device but no stimulation)

At the end of each stimulation session participants marked on a visual analogue scale (VAS) their perceived urge to swallow between a minimum of 1 with no urge to swallow and a maximum of 100 which is the highest urge to swallow possible. The Change in perceived urge to swallow when stimulation was presented minus the perceived urge to swallow following no stimulation was computed.

At the end of each stimulation session participants marked on a visual analogue scale (VAS) their perceived discomfort between a minimum of 1 with no discomfort and a maximum of 100 which is the highest discomfort possible. The Change in perceived discomfort when stimulation was presented minus the perceived discomfort following no stimulation was computed.

The pressure between the neck band and the skin was set and the changes in swallowing frequency was compared between pressure between increased pressure and no pressure condition

The pressure between the neck band and the skin was set and the changes in swallowing frequency was compared between increased pressure and no pressure condition

Percent Change= \[(Number of swallows per minute from continuous stimulation -number of swallows per minute during pulsed stimulation) / number of swallows per minute during pulsed stimulation\] X 100

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Training Swallowing Initiation During Expiration	NCT05278039	Head and Neck C... Dysphagia Oropharyngeal D... Oropharynx Squa...	Respiratory-Swa... Swallow Practic...	18 Years -	Northwestern University
QUantitative Assessment of Swallowing After Radiation (QUASAR)	NCT04359199	Head and Neck C... Dysphagia Oropharyngeal D... Oropharynx Canc... Oropharynx Squa...	Radiation Thera... Cetuximab Chemotherapy Immunotherapy	18 Years -	University of California, San Diego
Pharyngocise Dose Response Study	NCT01279837	Dysphagia	Pharyngocise	21 Years - 90 Years	University of Florida
Autologous Muscle Derived Cells for Treatment of Tongue Dysphagia	NCT05421689	Oropharyngeal D...	Autologous Musc... Placebo	18 Years -	University of California, Davis
Autologous Muscle Derived Cells for Treatment of Tongue Dysphagia	NCT05421689	Oropharyngeal D...	Autologous Musc... Placebo	18 Years -	University of California, Davis
Training Swallowing Initiation During Expiration	NCT05278039	Head and Neck C... Dysphagia Oropharyngeal D... Oropharynx Squa...	Respiratory-Swa... Swallow Practic...	18 Years -	Northwestern University
Autologous Muscle Derived Cells for Treatment of Tongue Dysphagia	NCT05421689	Oropharyngeal D...	Autologous Musc... Placebo	18 Years -	University of California, Davis
Respiratory-Swallow Training in Veterans With Oropharyngeal Cancer	NCT01032928	Oropharyngeal D... Oropharyngeal C...	Respiratory-Swa...	21 Years -	VA Office of Research and Development
The Passy Muir Swallowing Self Training Device	NCT01765673	Oropharyngeal D...	Vibrotactile st...	20 Years -	James Madison University
Training Swallowing Initiation During Expiration	NCT05278039	Head and Neck C... Dysphagia Oropharyngeal D... Oropharynx Squa...	Respiratory-Swa... Swallow Practic...	18 Years -	Northwestern University
Pharyngocise Dose Response Study	NCT01279837	Dysphagia	Pharyngocise	21 Years - 90 Years	University of Florida

Spots Global Cancer Trial Database for oropharyngeal dysphagia