Respiratory and Real-time Dynamics in Exercise-Induced Paradoxical Vocal Fold Motion (EILO)

The overall objectives of the proposed research are to:

1. Evaluate the diagnostic validity of a novel mechano-acoustic signatures of task-characteristic activity during symptomatic and asymptomatic breathing in Exercise-Induced Laryngeal Obstruction (EILO) patients with the use of a novel miniature, soft wearable skin-mounted device,
2. Identify the mechanism/s of paradoxical respiratory control in EILO by quantifying the relationship between pulmonary mechanics, partial pressure of carbon dioxide (PCO2) maintenance, and vocal fold aperture prior to and during symptomatic and asymptomatic exercise ventilation, and
3. Identify unique biophysiological factors contributing to EILO among exercisers with and without EILO. Findings will be highly novel and clinically significant for early identification and management of EILO.

The main study will enroll 60 participants with EILO and 60 without EILO to complete three separate visits:

1. Exercise treadmill study
2. Free running with the device on the neck
3. Undergoing MRI (Magnetic Resonance Imaging) of the vocal tract.

An additional substudy limited to the mechanoacoustic device will enroll 10 additional participants (5 healthy and 5 with EILO). These participants will complete a single study visit during which the mechano-acoustic device will be worn during four sequential conditions.

Study Overview

• Status: Recruiting
• Conditions: Vocal Cord Dysfunction; Paradoxical Vocal Fold Motion; Exercise-Induced Vocal Cord Dysfunction
• Intervention / Treatment: Drug: Carbon Dioxide; Device: Mechano-acoustic device

Detailed Description

Main Study

At the first study visit, participants will sign informed consent, complete study questionnaires, have their height, weight, and body composition measured, and perform resting pulmonary function tests. Participants will then warm up on the treadmill for 10 minutes. An endoscope will be placed in one nostril until the vocal folds are visible, and subjects will be fitted with a chest strap heart rate monitor, an oro-nasal face mask, and the mechanoacoustic device. This sensor is placed on the neck with a velcro band. Participants will then undergo a graded exercise test during which a carbon-dioxide enriched gas mixture will be administered. The amount of the gas mixture will be titrated based on measures of the participant's breathing and lung function. This visit will be video recorded.

At the second study visit, participants will be asked to again wear the mechanoacoustic device while free running for 10 minutes in a large room or on a track. This visit will be video-recorded.

At the third study visit, participants will be asked to undergo an MRI scan, during which they will perform a variety of breathing exercises including rest breathing, rapid breathing, pursed lip breathing, sniff, and open mouth breathing. Research personnel will instruct participants in the various breathing techniques prior to the scan.

Device Only Substudy

Participants will be evaluated using the mechanoacoustic device only at a single visit. Participants will wear the neck device during four sequential conditions: seated rest indoors (15 minutes); standing outdoors (15 minutes); walking outdoors (15 minutes); running outdoors (15 minutes). This visit will be video-recorded.

• Study Type: Interventional
• Enrollment (Estimated): 130
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Rita R Patel; Phone Number: 812-855-3886; Email: patelrir@iu.edu

Study Locations

• United States
  • Indiana
    • Bloomington, Indiana, United States, 47401
      • Recruiting
      • Indiana University
      • Contact: Rita Patel; Phone Number: 812-855-3886; Email: patelrir@iu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria for Exercise-Induced Laryngeal Obstruction (EILO):

• Physically active >2.5 hours per week
• Patients with EILO, as diagnosed by routine clinical examination by physician and/or speech language pathologist
• Age range of 18-26 years
• Greater difficulty breathing inside compared to out and difficulty breathing which is exacerbated at peak exercise and stops 1-5 minutes after exercise
• Score of 7 or higher on the Dyspnea Index, which is a validated instrument to capture participant self-report of upper airway dyspnea symptoms.
• Classified as low risk, based on the modified Physical Activity Readiness Questionnaire (PAR-Q) questionnaire, body mass index, and non-smoking status
• Negative history of voice disorders, self-report of cognitive difficulties, asthma or other lung disease, cardiac disease, serious orthopedic injuries, current uncontrolled hypertension, illicit drug use, seizure/epilepsy, claustrophobia, use of beta blockers.
• No metallic, mechanical or magnetic implants such as cardiac devices, cochlear, or other non-removable ear implants, any prosthesis, stents, deep brain stimulator, etc.

Inclusion Criteria for Controls

• Physically active >2.5 hours per week
• Age range of 18-26 years
• Classified as low risk, based on the modified PAR-Q questionnaire, body mass index, and non-smoking status
• Negative history of voice disorders, self-report of cognitive difficulties, asthma or other lung disease, cardiac disease, serious orthopedic injuries, current uncontrolled hypertension, illicit drug use, seizure/epilepsy, claustrophobia, use of beta blockers.
• No metallic, mechanical or magnetic implants such as cardiac devices, cochlear, or other non-removable ear implants, any prosthesis, stents, deep brain stimulator, etc.

Exclusion Criteria for EILO:

• Individuals older than 26 years and younger than 18 years of age.
• Women who are pregnant or could possibly be pregnant.
• BMI > 25 kg/m2
• A 'yes' answer to any of the 14 questions on the PAR-Q pre-participation questionnaire
• Current smoker
• Positive history of voice disorders, self-report of cognitive difficulties, asthma or other lung disease, cardiac disease, serious orthopedic injuries, current uncontrolled hypertension, illicit drug use, seizure/epilepsy, claustrophobia, use of beta blockers.
• Presence of metallic, mechanical or magnetic implants such as cardiac devices, cochlear, or other non-removable ear implants, any prosthesis, stents, deep brain stimulator, etc.
• Do not report the following: Greater difficulty breathing inside compared to out and difficulty breathing which is exacerbated at peak exercise and stops 1-5 minutes after exercise

Exclusion Criteria for Controls

• Individuals older than 26 years and younger than 18 years of age.
• Women who are pregnant or could possibly be pregnant.
• BMI > 25 kg/m2
• A 'yes' answer to any of the 14 questions on the PAR-Q pre-participation questionnaire
• Current smoker
• Positive history of voice disorders, self-report of cognitive difficulties, asthma or other lung disease, cardiac disease, serious orthopedic injuries, current uncontrolled hypertension, illicit drug use, seizure/epilepsy, claustrophobia, use of beta blockers.
• Presence of metallic, mechanical or magnetic implants such as cardiac devices, cochlear, or other non-removable ear implants, any prosthesis, stents, deep brain stimulator, etc.
• Significant acute or chronic medical, neurologic, or illness in the patient that, in the judgment of the Principal Investigator, could compromise subject safety, limit the ability to complete the study, and/or compromise the objectives of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control Participants; Participants without Exercise-induced laryngeal obstruction (EILO).	Drug: Carbon Dioxide; Breathing Hypercapnic Gas (10% CO2 (carbon dioxide) and 21%O2 (oxygen), balance N210% (nitrogen)); Device: Mechano-acoustic device; A custom developed mechanoacoustic sensor will be worn on the neck using a Velcro strap. The device will collect audio recordings of breathing and breath sounds and will collect muscle activity from the neck muscles.
Active Comparator: EILO Participants	Drug: Carbon Dioxide; Breathing Hypercapnic Gas (10% CO2 (carbon dioxide) and 21%O2 (oxygen), balance N210% (nitrogen)); Device: Mechano-acoustic device; A custom developed mechanoacoustic sensor will be worn on the neck using a Velcro strap. The device will collect audio recordings of breathing and breath sounds and will collect muscle activity from the neck muscles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Device measurements from real time running	Muscle activation of cricothyroid/sternohyoid muscle measured via customized surface electromyography amplifier	Baseline and Periprocedural
Device measurements from real time running	Normalized amplitude (100% of maximum voluntary contraction) Burst duration (milliseconds) prior to and during Exercise-Induced Laryngeal Obstruction event of laryngeal closure.	Baseline and Periprocedural
Device measurements from real time running	Exercise-Induced Laryngeal Obstruction signature detected via ultra-low noise micro-electromechanical (MEMS) microphone amplitude (dB) prior to and during EILO. EILO signature detected via accelerometer (g, where g represents the gravitational acceleration of 9.8 m/s2) prior to and during EILO	Baseline and Perioprocedural
Treadmill testing	Breathing frequency (breaths per minute)	Baseline and Perioprocedural
Treadmill testing	Tidal volume (Liters)	Base-line
Treadmill testing	Ventilation (Liters/minute)	Breath-by-breath baseline and Perioprocedural
Treadmill testing	Partial pressure of arterial carbon dioxide estimated from end-tidal partial pressure of carbon dioxide; PetCO2) (mmHg)	Baseline and Periprocedural
MRI Upper Airway Size	Length (mm), width (mm), and cross-sectional area (mm2) of oropharynx, supraglottis, glottis, immediate subglottis.	Baseline
Upper Airway Aerodynamics	pressure (Pa) across oropharynx, supraglottis, and subglottis	Baseline and Periprocedural
Upper Airway Aerodynamics	volume flow rate (l/s) across oropharynx, supraglottis, and subglottis	Baseline and Periprocedural
Upper Airway Aerodynamics	flow velocities (m/s) across oropharynx, supraglottis, and subglottis	Baseline and Periprocedural

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Self-rating of dyspnea	Dyspnea self-rating of breathing intensity and breathing unpleasantness rating on Visual Analog Scale of 0 to 100mm	Baseline

Collaborators and Investigators

• Sponsor: Indiana University
• Collaborators: National Institute on Deafness and Other Communication Disorders (NIDCD); Purdue University; National Jewish Health
• Investigators: Principal Investigator: Rita Patel, Indiana University

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2026
• Primary Completion (Estimated): January 20, 2032
• Study Completion (Estimated): January 20, 2032

Study Registration Dates

• First Submitted: January 13, 2026
• First Submitted That Met QC Criteria: February 11, 2026
• First Posted (Actual): February 19, 2026

Study Record Updates

• Last Update Posted (Actual): August 14, 2026
• Last Update Submitted That Met QC Criteria: August 12, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Otorhinolaryngologic Diseases; Laryngeal Diseases; Vocal Cord Dysfunction; Inorganic Chemicals; Oxides; Oxygen Compounds; Gases; Carbon Compounds, Inorganic; Carbon Dioxide
• Other Study ID Numbers: 29009; R01DC023381 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data will be available indefinitely, as per NIH's Data Management and Sharing Policy to maximize the appropriate sharing of scientific data.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No