Mechanisms of Pharyngeal Collapse in Sleep Apnea, Study A

• ClinicalTrials.gov Identifier: NCT01728974
• Recruitment Status: Completed
• First Posted: November 20, 2012
• Last Update Posted: July 11, 2019
• Sponsor: Brigham and Women's Hospital
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): David Andrew Wellman, Brigham and Women's Hospital

Tracking Information

• First Submitted Date: November 14, 2012
• First Posted Date: November 20, 2012
• Last Update Posted Date: July 11, 2019
• Actual Study Start Date: December 8, 2012
• Actual Primary Completion Date: December 26, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 19, 2012)

Negative effort dependence variation [ Time Frame: After pharyngeal topical anesthesia ]

The magnitude of negative effort dependence will be expressed as the percent decrease in inspiratory flow from Vmax. NED will be compared before and after topical upper airway anesthesia

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Mechanisms of Pharyngeal Collapse in Sleep Apnea, Study A
• Official Title: Mechanisms of Pharyngeal Collapse in Sleep Apnea
• Brief Summary: In obstructive sleep apnea, the upper airway recurrently closes during sleep. The mechanisms that lead to airway closure are not completely understood. While the airway of some people narrows and airflow decreases during inspiration due to increasing inspiratory effort, others maintain constant airflow throughout inspiration. Airway neuromuscular reflexes may protect against airway narrowing that occurs due to increasing inspiratory effort. To test this hypothesis, the investigators will initially measure airway neuromuscular reflex and inspiratory flow and then attenuate neuromuscular reflex through topical pharyngeal anesthesia to observe the effects on inspiratory flow.

Detailed Description

The mechanisms that lead to airway closure are not completely understood. While the airway of some people narrows and airflow decreases during inspiration due to increasing inspiratory effort, others maintain constant airflow throughout inspiration (negative effort dependence, NED). The investigators hypothesize that upper airway neuromuscular reflexes may protect against narrowing that occurs due to increasing inspiratory effort. Topical oropharyngeal anesthesia has been shown to reduce neuromuscular reflexes. Thus, the investigators also hypothesize that patients with stable inspiratory flow will develop NED once the reflexes have been impaired with topical anesthetic. The investigators plan to:

1. measure upper airway muscle EMG to assess how it corresponds to the presence or absence of NED. This aim will allow us to test the hypothesis that robust upper airway muscle reflexes can protect against NED.
2. reduce upper airway muscle activity and reflexes by topical oropharyngeal anesthesia. This will allow us to test the hypothesis that attenuated upper airway muscle activity induced by topical anesthesia can induce NED.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Other

Condition

• Obstructive Sleep Apnea
• Pathophysiology

Intervention

Other: Pharyngeal topical anesthesia

Pharyngeal topical anesthesia will be performed using 4% lidocaine spray

Study Arms

Experimental: Pharyngeal topical anesthesia

Pharyngeal topical anesthesia will be performed using 4% lidocaine spray

Intervention: Other: Pharyngeal topical anesthesia

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 9, 2019): 26
• Original Estimated Enrollment (submitted: November 19, 2012): 20
• Actual Study Completion Date: December 26, 2018
• Actual Primary Completion Date: December 26, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Normal subjects or patients with OSA

Exclusion Criteria:

• Any unstable cardiac condition (other than well controlled hypertension) or pulmonary problems.
• Any medication known to influence breathing, sleep/arousal or muscle physiology
• Concurrent sleep disorders (insomnia, narcolepsy, central sleep apnea or parasomnia)
• Claustrophobia
• Inability to sleep supine
• Allergy to lidocaine or oxymetazoline HCl
• For women: Pregnancy

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01728974
• Other Study ID Numbers: 2012P000957A; 1R01HL102321-01A1 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: David Andrew Wellman, Brigham and Women's Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Brigham and Women's Hospital
• Original Study Sponsor: Same as current
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: David A Wellman; Brigham and Women's Hospital

• PRS Account: Brigham and Women's Hospital
• Verification Date: July 2019