Effects of Lung Volume on Upper Airway Patency During Drug Induced Sleep Endoscopy

NCT ID: NCT05350332

Last Updated: 2025-10-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-30
• Study Completion Date: 2026-06-30

Brief Summary

Obstructive sleep apnea (OSA) is a disorder where a person has recurrent choking episodes during sleep. Surgery can treat OSA and drug induced sleep endoscopy (DISE) is a procedure that surgeons use to evaluate the throat while a person is sedated, mimicking sleep, to help determine if surgery might be effective. Lung volume can influence OSA severity but the relationship between lung function and throat collapse seen on DISE has not been well studied. This study aims to see if lung volume influences what is happening in the throat during DISE. Participants will be recruited from the sleep surgery clinic where they are being evaluated for surgery to treat their OSA. Participants will have a DISE that is performed as part of their routine surgical workup for treatment of OSA. Additionally, during the DISE, they will participate in one of two study groups. One group will have a negative pressure "turtle shell" ventilator placed over the participants chest during DISE to manipulate lung volumes to see if it can improve throat collapse. A second group will have electrodes placed over the neck to stimulate the phrenic nerve to contract the diaphragm to improve lung volumes to see if it can improve throat collapse. Both groups will also have a lung function test performed.The findings of this study will be important in improving pre-surgical evaluation of patients to better predict if surgery can help as well as potentially develop new surgical therapies for the treatment of OSA.

Detailed Description

Obstructive sleep apnea (OSA) is a common disorder characterized by recurrent choking episodes during sleep. OSA affects over 25 million Americans and is associated with increased risks of hypertension, diabetes, cardiovascular disease, and stroke. The severity of OSA is measured by the number of complete or partial obstructive events per hour of sleep, and quantified for diagnostic and research purposes as the apnea-hypopnea index (AHI). Continuous positive airway pressure (CPAP) is the first line therapy for treating OSA, however, 20-40% of patients do not tolerate wearing a pressurized mask during sleep. Several surgeries can treat OSA, including pharyngeal soft tissue surgery, skeletal advancement surgery, and hypoglossal nerve stimulation which are deemed successful when surgery reduces the AHI to below 5 events per hour. Successful surgical treatment of OSA is highly variable with rates of success as low as 40% in early studies that looked at pharyngeal soft tissue surgery. Selecting OSA patients for surgery based on certain pathophysiologic characteristics has vastly improved surgical success rates, up to 60-80% depending on the surgery. However, the application of OSA pathophysiological assessment for surgical selection remains incomplete. This study will explore a wider range of pathophysiological factors to improve surgical outcomes and anticipate that further understanding of these relationships will support development of new surgical and non-surgical treatments for those who may not benefit from current treatment options.

Drug induced sleep endoscopy (DISE) is currently used to help determine appropriate patients for OSA surgery. During DISE, a fiber optic camera is placed through the nose into the throat to visualize airway collapse patterns during sedation mimicking natural sleep. The standardized method of describing airway collapse is known as the Velum, Oropharynx, Tongue Base, Epiglottis (VOTE) score which assesses the severity and pattern of collapse at four different anatomic sites of the upper airway. Previous studies have shown that airway collapse patterns visualized on DISE affect surgical outcomes.

Prior studies indicate that the phrenic nerve can be stimulated non-invasively to examine effects of diaphragmatic contraction on upper airway patency. Initial studies demonstrated that surface electrodes overlying the phrenic nerves in the lateral neck can be used to recruit the diaphragm and generate tidal breaths. Later studies demonstrated similar effects of transcutaneous stimulation with inductance coils on tidal airflow while modeling the effects of vigorous diaphragmatic contraction on pharyngeal patency. Finally, transcutaneous phrenic nerve stimulation has been applied during drug-induced sleep studies in patients to elucidate effects of lung volume on pharyngeal patency. This study demonstrated substantial reductions in upper airway obstruction in a dose-dependent fashion when phrenic nerve stimulation increased lung volume to varying levels. Of note, no untoward adverse events were noted in any of these prior studies. Taken together, these studies demonstrate that external transcutaneous stimulation is safe, can generate transient and sustained elevations in lung volume, and relieve upper airway obstruction in sedated individuals.

One overlooked pathophysiologic factor in the evaluation for OSA surgery is lung volume. Studies of lung physiology in OSA patients have found that lower functional residual capacity (FRC) and expiratory reserve volume (ERV) on pulmonary function testing, a commonly used procedure in pulmonary medicine, is associated with increased OSA severity. Experimental studies in OSA patients have shown that when negative pressure was used to expand the chest (e.g., iron lung) during sleep, the subsequent increased lung volume resulted in decreased upper airway collapsibility and reduced OSA severity. Transcutaneous phrenic nerve stimulation has also been applied during sedation studies in patients to elucidate effects of lung volume on pharyngeal patency demonstrating substantial reductions in upper airway obstruction in a dose-dependent fashion when phrenic nerve stimulation increased lung volume to varying levels. Despite this evidence, lung volume is not utilized as part of the evaluation for OSA surgery. The goal of this study is to determine if lung volume is useful in predicting surgical success and whether improving lung volumes via negative pressure ventilator or phrenic nerve stimulation can be used as an adjunctive therapy with surgery to treat OSA.

Patients will participate in DISE and be assigned either into a negative pressure ventilator or phrenic nerve stimulation cohort to evaluate each modality's effect on improving lung volume and altering upper airway collapsibility in DISE. Participants will also have a pulmonary function test to determine baseline lung volume measures.

Conditions

Obstructive Sleep Apnea

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Negative Pressure Ventilator

Participants with obstructive sleep apnea (OSA) who are being evaluated for surgical treatment of their OSA and having a routine clinical DISE will have their lung volume increased with a non-invasive negative pressure ventilator. Participants will also have a pulmonary function test performed per routine clinical protocol, but for research purposes only (i.e., not part of usual care).

Group Type: EXPERIMENTAL

Negative Pressure Ventilator

Intervention Type: DEVICE

The negative pressure ventilator is an off-the-shelf FDA-approved device designed to treat respiratory patients with hypoventilation syndromes. This ventilator places the torso within a fixed container that is connected to a vacuum source, which inflates the lungs by pulling a negative pressure around the chest and abdomen. After the clinically routine DISE, a negative pressure ventilator will be placed on the participant's chest to increase lung volumes and the DISE evaluation will be repeated to observe changes.

Pulmonary Function Testing (PFT)

Intervention Type: DEVICE

PFT is a routine standardized clinical test evaluating lung function, consisting of two parts: spirometry and body plethysmography. In spirometry, participants breathe through a mouthpiece that measures airflow and volume to determine normal and maximal volume of inspiration/expiration. Body plethysmography is performed to calculate residual lung volumes. Participants enter in an enclosed chamber where they breathe through a mouthpiece. Changes in pressure in the sealed chamber during breathing are used to calculate the volume of air that remains in the lung after expiration. A MiniBox+ device may be used. The MiniBox+ device derives total lung capacity (TLC) during tidal breathing by the analysis of gas pressures and airflows immediately preceding and immediately following airway occlusions to calculate the same measures as conventional PFT analysis.

Transcutaneous Phrenic Nerve Stimulation

Participants with obstructive sleep apnea (OSA) who are being evaluated for surgical treatment of their OSA and having a routine clinical DISE will have their lung volume increased with transcutaneous phrenic nerve stimulation. Participants will also have a pulmonary function test performed per routine clinical protocol, but for research purposes only (i.e., not part of usual care).

Group Type: EXPERIMENTAL

Pulmonary Function Testing (PFT)

Intervention Type: DEVICE

PFT is a routine standardized clinical test evaluating lung function, consisting of two parts: spirometry and body plethysmography. In spirometry, participants breathe through a mouthpiece that measures airflow and volume to determine normal and maximal volume of inspiration/expiration. Body plethysmography is performed to calculate residual lung volumes. Participants enter in an enclosed chamber where they breathe through a mouthpiece. Changes in pressure in the sealed chamber during breathing are used to calculate the volume of air that remains in the lung after expiration. A MiniBox+ device may be used. The MiniBox+ device derives total lung capacity (TLC) during tidal breathing by the analysis of gas pressures and airflows immediately preceding and immediately following airway occlusions to calculate the same measures as conventional PFT analysis.

Transcutaneous Phrenic Nerve Stimulation

Intervention Type: DEVICE

Phrenic nerve stimulation (PNS) will be performed transcutaneously using a commercially available and FDA approved peripheral neurostimulator. (Digitimer DS8R Bipolar Constant Current Stimulator). The neurostimulator consists of a stimulation generating box connected to electrodes that will be placed over the skin of the neck bilaterally over both phrenic nerves where an bipolar electric current will be used to stimulate the phrenic nerve leading to diaphragm contraction.

Interventions

Negative Pressure Ventilator

The negative pressure ventilator is an off-the-shelf FDA-approved device designed to treat respiratory patients with hypoventilation syndromes. This ventilator places the torso within a fixed container that is connected to a vacuum source, which inflates the lungs by pulling a negative pressure around the chest and abdomen. After the clinically routine DISE, a negative pressure ventilator will be placed on the participant's chest to increase lung volumes and the DISE evaluation will be repeated to observe changes.

Intervention Type: DEVICE

Pulmonary Function Testing (PFT)

PFT is a routine standardized clinical test evaluating lung function, consisting of two parts: spirometry and body plethysmography. In spirometry, participants breathe through a mouthpiece that measures airflow and volume to determine normal and maximal volume of inspiration/expiration. Body plethysmography is performed to calculate residual lung volumes. Participants enter in an enclosed chamber where they breathe through a mouthpiece. Changes in pressure in the sealed chamber during breathing are used to calculate the volume of air that remains in the lung after expiration. A MiniBox+ device may be used. The MiniBox+ device derives total lung capacity (TLC) during tidal breathing by the analysis of gas pressures and airflows immediately preceding and immediately following airway occlusions to calculate the same measures as conventional PFT analysis.

Intervention Type: DEVICE

Transcutaneous Phrenic Nerve Stimulation

Phrenic nerve stimulation (PNS) will be performed transcutaneously using a commercially available and FDA approved peripheral neurostimulator. (Digitimer DS8R Bipolar Constant Current Stimulator). The neurostimulator consists of a stimulation generating box connected to electrodes that will be placed over the skin of the neck bilaterally over both phrenic nerves where an bipolar electric current will be used to stimulate the phrenic nerve leading to diaphragm contraction.

Intervention Type: DEVICE

Other Intervention Names

cuirass ventilator; Hayek turtle shell; iron lung; MiniBox+

Eligibility Criteria

Inclusion Criteria

• Adult patients (≥ 18 yrs) willing and capable of providing informed consent
• Obstructive sleep apnea (AHI ≥ 5 events/hour)
• Must be willing and able to provide informed consent to participate in the study.
• Interested in surgical treatments of OSA and have consented for a DISE procedure as part of their routine clinical evaluation.

• Patients are evaluated and cleared by anesthesia prior to the procedure.

Exclusion Criteria

• No significant uncontrolled medical co-morbidities (e.g., uncontrolled hypertension, unstable angina, uncompensated heart failure or COPD).
• Any medical comorbidity that would prevent the patient from receiving anesthesia or having surgery
• Inability to tolerate negative pressure ventilator or perform PFT (i.e. claustrophobia)
• No incapacitating disability that interferes with execution of the protocol

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Lunair Medical

INDUSTRY

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Jason Yu

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jason Yu, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Emory University Hospital Midtown

Atlanta, Georgia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jason Yu, MD

Role: CONTACT

jyu40@emory.edu

470-763-3887

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Other Identifiers

STUDY00003579

Identifier Type: -

Identifier Source: org_study_id