Delineating Swallowing Impairment and Decline in ALS

• ClinicalTrials.gov Identifier: NCT02962050
• Recruitment Status: Completed
• First Posted: November 11, 2016
• Last Update Posted: February 23, 2023
• Sponsor: University of Florida
• Collaborator: National Institute of Neurological Disorders and Stroke (NINDS)
• Information provided by (Responsible Party): University of Florida

Tracking Information

• First Submitted Date: November 4, 2016
• First Posted Date: November 11, 2016
• Last Update Posted Date: February 23, 2023
• Actual Study Start Date: May 31, 2017
• Actual Primary Completion Date: February 16, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 13, 2020)

Global Swallowing Function [ Time Frame: Baseline, every 3 months through study completion, an average of 2 years. ]

The DIGEST scale will be used by trained, blinded raters to assign ratings of safety to bolus trials. Both efficiency and safety will be assigned a score from 0-4 (more safe/efficient - less safe/efficient) and based on these ratings, will be given a total score ranging from 0-4 that captures their DIGEST rating.

Original Primary Outcome Measures (submitted: November 8, 2016)

• Change in Maximum Swallowing Pressure with High Resolution Manometry (HRM) [ Time Frame: Baseline, every 3 months through study completion, an average of 2 years. ]
  HRM will measures maximum pressure (mmHg) across 4 anatomical zones.
• Change in Rate of Pressure with High Resolution Manometry (HRM) [ Time Frame: Baseline, every 3 months through study completion, an average of 2 years. ]
  HRM will measure rate of pressure (mmHg) increase across 4 anatomical swallowing zones.
• Change in Mean Pressure with High Resolution Manometry (HRM) [ Time Frame: Baseline, every 3 months through study completion, an average of 2 years. ]
  HRM will measure mean pressure (mmHg) across 4 anatomical swallowing zones.
• Swallowing Safety (with DIGEST) [ Time Frame: Baseline, every 3 months through study completion, an average of 2 years. ]
  The validated DIGEST scale will be used by trained, blinded raters to assign ratings of safety to bolus trials. Both efficiency and safety will be assigned a score from 0-4 (more safe/efficient - less safe/efficient) and based on these ratings, will be given a total score ranging from 0-4 that captures their DIGEST rating.
• Swallowing Efficiency (with DIGEST) [ Time Frame: Baseline, every 3 months through study completion, an average of 2 years. ]
  The validated DIGEST scale will be used by trained, blinded raters to assign ratings of efficiency to bolus trials. Both efficiency and safety will be assigned a score from 0-4 (more safe/efficient - less safe/efficient) and based on these ratings, will be given a total score ranging from 0-4 that captures their DIGEST rating.
• Swallowing Efficiency (with NRRS) [ Time Frame: Baseline, every 3 months through study completion, an average of 2 years. ]
  The validated Normalized Residue Ratio Scale (NRRS) is a validated measurement tool that is used to quantify the amount of residue remaining in the valleculae and pyriform sinus after bolus trials. Inefficient swallows are those swallows with an NRRS valleculae (NRRSv) rating of 0.07 or greater and an NRRS pyriform sinus (NRRSp) rating of 0.2 or greater. Efficient swallows will be those calculated to have an NRRSv value of <.07 and/or NRRSp value of <.02.
• Swallowing Safety (with PAS) [ Time Frame: Baseline, every 3 months through study completion, an average of 2 years. ]
  The Penetration Aspiration scale is an 8-point, interval scale that will be used by trained, blinded to assign ratings of safety to swallowing bolus trials. Unsafe PAS scores will be those greater than 3 and safe scores are those assigned a rating of 1 or 2.
• Change in Forced Vital Capacity with Pulmonary Function Testing (with hand-held digital manometer) [ Time Frame: Baseline, every 3 months through study completion, an average of 2 years. ]
  Pulmonary function testing will be used to determine forced vital capacity (FVC).
• Voluntary Peak Cough Flow Testing (with Electronic Peak Cough Flow Meter Device) [ Time Frame: Baseline, every 3 months through study completion, an average of 2 years. ]
  Voluntary peak cough flow testing will be used to capture the volume of air expelled in the 1st second of cough as measured in PEF and FEV1.
• Change in Lingual Strength with Lingual Function Testing (with IOPI) [ Time Frame: Baseline, every 3 months through study completion, an average of 2 years. ]
  Lingual function testing will be used to measure maximum anterior lingual pressure (kPA).
• Change in Lingual Physiologic Reserve with Lingual Function Testing (IOPI) [ Time Frame: Baseline, every 3 months through study completion, an average of 2 years. ]
  Lingual function testing will be used to measure lingual physiologic functional reserve (kPA)
• Change in Lingual Swallowing Pressure with Lingual Function Testing (IOPI) [ Time Frame: Baseline, every 3 months through study completion, an average of 2 years. ]
  Lingual strength testing will be used to measure lingual pressure during swallowing (kPA).
• Change in Lingual Resistance with Lingual Electrical Impedance Myography (with SFB7 ImpediMed device) [ Time Frame: Baseline, every 3 months through study completion, an average of 2 years. ]
  Lingual EIM will be used to assess the health of the lingual musculature by assessing this muscle using an electrode that will apply a current and a frequency spectrum ranging from 500 Hz to 2 MHz will be analyzed to determine resistance (Ohms) of the tongue.
• Change in Lingual Reactance with Lingual Electrical Impedance Myography (EIM) [ Time Frame: Baseline, every 3 months through study completion, an average of 2 years. ]
  Lingual EIM will be used to assess the health of the lingual musculature by assessing this muscle using an electrode that will apply a current and a frequency spectrum ranging from 500 Hz to 2 MHz will be analyzed to determine reactance (Ohms) of the tongue.
• Change in Phase Angle with Lingual Electrical Impedance Myography (EIM) [ Time Frame: Baseline, every 3 months through study completion, an average of 2 years. ]
  Lingual EIM will be used to assess the health of the lingual musculature by assessing this muscle using an electrode that will apply a current and a frequency spectrum ranging from 500 Hz to 2 MHz will be analyzed to determine phase angle (degrees) of the tongue.
• Change in Reflexive Cough Testing (with Urge-to-Cough) [ Time Frame: Baseline, every 3 months through study completion, an average of 2 years. ]
  Reflexive cough testing will use a capsaicin challenge that will assess individual's cough motor and cough sensory thresholds. A modified Borg scale ranging from 0 (no cough) to 10 (maximal urge to cough) will be used to quantify these thresholds. A cough sensory threshold will be defined as a concentration of capsaicin eliciting a perceived urge to cough of 1 (very slight) >2/3 trials. A cough motor threshold will be the lowest concentration of capsaicin eliciting >2 cough responses in 2/3 trials.
• Change in Maximum Expiratory Pressure with Pulmonary Function Testing (with hand-held digital manometer) [ Time Frame: Baseline, every 3 months through study completion, an average of 2 years. ]
  Pulmonary Function Testing will be used to determine maximum expiratory pressure (MEP).
• Change in Maximum Inspiratory Pressure with Pulmonary Function Testing (with hand-held digital manometer) [ Time Frame: Baseline, every 3 months through study completion, an average of 2 years. ]
  Pulmonary function testing will be used to determine maximum inspiratory pressure (MIP).

• Current Secondary Outcome Measures: Not Provided

Original Secondary Outcome Measures (submitted: November 8, 2016)

• Eating Assessment Tool 10 [ Time Frame: Baseline, every 3 months through study completion, an average of 2 years. ]
  The Eating Assessment Tool 10 will be used to allow patients to rate their perception of 10 swallowing symptoms on a scale from 0 (no problem) to 4 (severe problem). An EAT-10 score of 3 or higher might be indicative of swallowing safety and efficiency problems.
• Center for Neurologic Study Bulbar Function Scale [ Time Frame: Baseline, every 3 months through study completion, an average of 2 years. ]
  The CNS-BFS is a scale that allows patients to self report perceptions regarding three domains (swallowing, speech and salivation). Each domain contains perceptual ratings ranging from 1-7 with 7 considered the worst.
• The Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) [ Time Frame: Baseline, every 3 months through study completion, an average of 2 years. ]
  The ALSFRS-R is a 12-item questionnaire that provides information regarding bulbar, limb, and respiratory function in persons as disease progresses. Each question is rated on a scaled ranging from 4 (better) to 0 (worst). Scores are calculated and expressed out of 48 total points.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Delineating Swallowing Impairment and Decline in ALS
• Official Title: Delineating Physiologic Mechanisms of Swallowing Impairment and Decline in ALS
• Brief Summary: The purpose of this study is to 1) evaluate the discriminant ability of simple clinical markers to detect swallowing impairment in individuals with ALS, 2) develop and validate a minimally invasive clinical screening tool for use at multidisciplinary ALS clinics, and 3) determine the natural history of swallowing impairment and decline in ALS.

Detailed Description

This research study is being performed to determine screening tools or tests that are able to identify and track swallowing problems associated with Amyotrophic Lateral Sclerosis (ALS) over time. Also, this study will provide insight into the natural progression of swallowing impairment in persons with ALS over time.

Participants enrolled in this study will complete an evaluation at the University of Florida Aerodigestive Research Core laboratory located at Shands Hospital, Gainesville every three months. Each evaluation will take approximately 90 minutes. During these evaluations, a videofluoroscopy (X-ray of swallowing) examination, cough tests and questionnaires will be completed.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: Individuals with Amyotrophic Lateral Sclerosis
• Condition: Amyotrophic Lateral Sclerosis

Intervention

• Procedure: Videofluoroscopic Swallowing Study (VFSS)
  Videofluoroscopic swallowing study will be performed to measure oropharyngeal swallowing
  Other Names:

  • VFSS
  • X-Ray of Swallowing
  • Modified Barium Swallow Study
• Device: Voluntary Peak Cough Flow Testing
  Voluntary peak cough flow testing will be performed to determine the peak expiratory flow (PEF) and volume of air expelled (FEV1) during voluntary coughing.
• Device: Iowa Oral Performance Instrument
  The Iowa Oral Performance Instrument (IOPI) is a device that measures the peak pressure performance of lingual strength and endurance via the action of a bulb placed on the hard palate.
  Other Name: IOPI
• Drug: Capsaicin Challenge
  A capsaicin challenge with three randomized blocks of 0, 50, 100, 200, and 500 μM capsaicin. The capsaicin will be dissolved in a vehicle solution consisting of 80% physiological saline, and 20% ethanol. Participants will be given the instruction "cough if you need to" prior to capsaicin delivery.The solution will be administered automatically upon detection of an inspired breath and there will be a minimum of one minute between each trial. This is to test the reflexive cough testing for upper airway sensitivity and motor thresholds.
  Other Name: Reflexive Cough Testing
• Device: Pulmonary Function Testing
  Pulmonary Function testing will be performed using conventional methods and will include the following outcomes: forced vital capacity (FVC), maximum inspiratory pressure (MIP), and maximum expiratory pressure (MEP) expressed as a percentage of predicted values.
• Other: Eating Assessment Tool 10
  The Eating Assessment Tool-10 will be used for participant reporting of swallowing system severity.
  Other Name: EAT 10
• Other: The Center for Neurologic Study Bulbar Function Scale
  The Center for Neurologic Studies Bulbar Function Scale (CNS-BFS) will be used to report bulbar function in study participants.
  Other Name: CNS-BFS

Study Groups/Cohorts

ALS

Participants enrolled will complete the following tests: Videofluoroscopic Swallowing Study, Voluntary Peak Cough Flow Testing, lingual strength and endurance trials using the Iowa Oral Performance Instrument, reflexive cough testing, Pulmonary Function Testing; Eating Assessment Tool-10 (EAT-10), Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R), and the The Center for Neurologic Study Bulbar Function Scale (CNS-BFS).

Interventions:

• Procedure: Videofluoroscopic Swallowing Study (VFSS)
• Device: Voluntary Peak Cough Flow Testing
• Device: Iowa Oral Performance Instrument
• Drug: Capsaicin Challenge
• Device: Pulmonary Function Testing
• Other: Eating Assessment Tool 10
• Other: The Center for Neurologic Study Bulbar Function Scale

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 22, 2023): 109
• Original Estimated Enrollment (submitted: November 8, 2016): 100
• Actual Study Completion Date: February 16, 2023
• Actual Primary Completion Date: February 16, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• diagnosis of probable or definite ALS

Exclusion Criteria:

• allergies to barium or capsaicin
• History of stroke
• Head and Neck Cancer
• Other disorder that might contribute to swallowing impairment
• Not enrolled in other research investigations that might impact swallowing
• Not pregnant

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 90 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02962050
• Other Study ID Numbers: IRB201602098-N; R01NS100859 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: University of Florida
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Florida
• Original Study Sponsor: Same as current
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

• Principal Investigator: Emily Plowman, PhD; University of Florida

• PRS Account: University of Florida
• Verification Date: February 2023