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

Obstructive Sleep Apnea Clinical Trial

— DISE-Pulm  

Official title:

Characterizing the Effects of Lung Volume on Upper Airway Patency During Drug Induced Sleep Endoscopy in Patients With Obstructive Sleep Apnea

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05350332
• Other study ID #: STUDY00003579
• Status: Recruiting
• Phase: N/A
• Start date: June 30, 2022
• Est. completion date: June 2024

Study information

• Verified date: September 2023
• Source: Emory University
• Contact: Jason Yu, MD
• Phone: 470-763-3887
• Email: jyu40[@]emory.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: June 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.
• Coronavirus disease 2019 (COVID-19) vaccinated subjects or subjects with a negative COVID-19 polymerase chain reaction (PCR) test as directed by the pre-procedure clearance policy at the institution.

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

Related Conditions & MeSH terms

• Obstructive Sleep Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

Device:
• 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.
• Pulmonary Function Testing (PFT)
PFT is a routine standardized clinical test to evaluate lung function. PFT is an outpatient procedure that consist of two parts: spirometry and body plethysmography. In spirometry, participants are asked to breathe through a mouthpiece that measures airflow and volume. Several breathing maneuvers are used to determine normal and maximal volume of inspiration/expiration. Body plethysmography is performed to calculate residual lung volumes. Participants are placed in an enclosed chamber where they are asked again to breathe through a mouthpiece. Changes in pressure in the sealed chamber during breathing can be used to calculate the volume of air that remains in the lung after expiration. The combination of values measured on spirometry and body plethysmography allow for calculation of residual lung volumes including the functional residual capacity and expiratory reserve volume.
• Transcutaneous Phrenic Nerve Stimulation
Phrenic nerve stimulation (PNS) will be performed trancutaneously using a commercially available and FDA approved peripheral neurostimulator. (Digitimer DS7A High Voltage Constant Current Stimulators). 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.

Locations

Country	Name	City	State
United States	Emory University Hospital Midtown	Atlanta	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Emory University

Country where clinical trial is conducted

United States, 

References & Publications (15)

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Heinzer RC, Stanchina ML, Malhotra A, Jordan AS, Patel SR, Lo YL, Wellman A, Schory K, Dover L, White DP. Effect of increased lung volume on sleep disordered breathing in patients with sleep apnoea. Thorax. 2006 May;61(5):435-9. doi: 10.1136/thx.2005.052084. Epub 2006 Feb 20. — View Citation

Iber, Conrad, Ancoli-Israel, Sonia, Chesson, Andrew L, Quan, Stuart F. The AASM manual for the scoring of sleep and associated events: rules, terminology and technical specifications. Am Acad Sleep Med Westchest IL. 2007;1.

Owens RL, Malhotra A, Eckert DJ, White DP, Jordan AS. The influence of end-expiratory lung volume on measurements of pharyngeal collapsibility. J Appl Physiol (1985). 2010 Feb;108(2):445-51. doi: 10.1152/japplphysiol.00755.2009. Epub 2009 Nov 25. — View Citation

Pepin JL, Woehrle H, Liu D, Shao S, Armitstead JP, Cistulli PA, Benjafield AV, Malhotra A. Adherence to Positive Airway Therapy After Switching From CPAP to ASV: A Big Data Analysis. J Clin Sleep Med. 2018 Jan 15;14(1):57-63. doi: 10.5664/jcsm.6880. — View Citation

Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000 May 11;342(19):1378-84. doi: 10.1056/NEJM200005113421901. — View Citation

Punjabi NM, Shahar E, Redline S, Gottlieb DJ, Givelber R, Resnick HE; Sleep Heart Health Study Investigators. Sleep-disordered breathing, glucose intolerance, and insulin resistance: the Sleep Heart Health Study. Am J Epidemiol. 2004 Sep 15;160(6):521-30. doi: 10.1093/aje/kwh261. — View Citation

Punjabi NM. The epidemiology of adult obstructive sleep apnea. Proc Am Thorac Soc. 2008 Feb 15;5(2):136-43. doi: 10.1513/pats.200709-155MG. — View Citation

Richards D, Bartlett DJ, Wong K, Malouff J, Grunstein RR. Increased adherence to CPAP with a group cognitive behavioral treatment intervention: a randomized trial. Sleep. 2007 May;30(5):635-40. doi: 10.1093/sleep/30.5.635. — View Citation

Series F, Cormier Y, Lampron N, La Forge J. Increasing the functional residual capacity may reverse obstructive sleep apnea. Sleep. 1988 Aug;11(4):349-53. — View Citation

Veasey SC, Rosen IM. Obstructive Sleep Apnea in Adults. N Engl J Med. 2019 Apr 11;380(15):1442-1449. doi: 10.1056/NEJMcp1816152. No abstract available. — View Citation

Verse T, Kroker BA, Pirsig W, Brosch S. Tonsillectomy as a treatment of obstructive sleep apnea in adults with tonsillar hypertrophy. Laryngoscope. 2000 Sep;110(9):1556-9. doi: 10.1097/00005537-200009000-00029. — View Citation

Weaver TE, Grunstein RR. Adherence to continuous positive airway pressure therapy: the challenge to effective treatment. Proc Am Thorac Soc. 2008 Feb 15;5(2):173-8. doi: 10.1513/pats.200708-119MG. — View Citation

Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM, Mohsenin V. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med. 2005 Nov 10;353(19):2034-41. doi: 10.1056/NEJMoa043104. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Expiratory Reserve Volume (ERV)	ERV is the volume of extra air that can be forcefully breathed out after exhaling normally. ERV is impacted by body size and altitude and the normal range for adults is about 0.7 to 1.1 liters (L). ERV is obtained as part of the pulmonary function test.	During PFT
Primary	Functional Residual Capacity (FRC)	FRC is the amount of air remaining in the lungs after a normal exhalation. FRC is impacted by body size and altitude and the normal volume for adults is about 1.8 to 2.4 L. FRC is obtained during the pulmonary function test and is the sum of residual volume (RV; the volume of air remaining after maximum exhalation) and ERV.	During PFT
Primary	Change in VOTE Collapse Patterns - Degree of Obstruction	VOTE collapse patterns are obtained during the routine clinical DISE evaluation and during DISE with negative pressure ventilation. The VOTE classification codes degree of obstruction as 0 = no obstruction (no vibration), 1 = partial obstruction (vibration), and 2 = complete obstruction (collapse). Degree of obstruction is determined the velum, oropharynx lateral walls, tongue base, and epiglottis. The measurements obtained without and with negative pressure ventilation will be compared.	During clinical DISE and intervention DISE
Primary	Change in VOTE Collapse Patterns - Configuration of Obstruction	VOTE collapse patterns are obtained during the routine clinical DISE evaluation and during DISE with negative pressure ventilation. The VOTE classification codes configuration of obstruction for structures with a degree of obstruction greater than 0. The configuration of obstruction is categorized as anteroposterior (anterior structures moving posteriorly against pharyngeal wall), lateral (lateral structures moving towards airway center), or concentric (both anteroposterior and lateral movements). The measurements obtained without and with negative pressure ventilation will be compared.	During clinical DISE and intervention DISE
Primary	Change in Critical Closing Pressure (Pcrit)	Critical closing pressures are obtained during the routine clinical DISE evaluation and during DISE with negative pressure ventilation. Pcrit assessed pharyngeal collapsibility and is measured as centimeters of water (cm H2O). A Pcrit of less than -10 cm H2O indicates normal breathing. Patients with a Pcrit around -6cm H2O tend to snore but not have OSA. A Pcrit around or greater than 0 cm H2O is seen with obstructive sleep apnea.The measurements obtained without and with negative pressure ventilation will be compared.	During clinical DISE and intervention DISE
Primary	Change in Pharyngeal Opening Pressures	Pharyngeal opening pressures are obtained during the routine clinical DISE evaluation and during DISE with negative pressure ventilation. Opening pressures are obtained using a positive airway pressure (PAP) titration device. Pharyngeal opening pressures are defined as the minimally effective positive airway pressure that results in non-flow limited breathing. This is measured in cm H2O and ranges from 0 to 25 cm H2O, with 25 cm H2O being the maximum pressure the PAP machine is capable of generating. The measurements obtained without and with negative pressure ventilation will be compared.	During clinical DISE and intervention DISE