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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Obstructive Sleep Apnea; Pathophysiology	Other: Pharyngeal topical anesthesia	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 26 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Mechanisms of Pharyngeal Collapse in Sleep Apnea
• Actual Study Start Date: December 8, 2012
• Actual Primary Completion Date: December 26, 2018
• Actual Study Completion Date: December 26, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Pharyngeal topical anesthesia; Pharyngeal topical anesthesia will be performed using 4% lidocaine spray	Other: Pharyngeal topical anesthesia; Pharyngeal topical anesthesia will be performed using 4% lidocaine spray

Outcome Measures

Primary Outcome Measures :

1. 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

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

United States, Massachusetts

Brigham and Women's Hospital

Boston, Massachusetts, United States, 02115

Sponsors and Collaborators

Brigham and Women's Hospital

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

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

More Information

• Responsible Party: David Andrew Wellman, Andrew Wellman, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT01728974
• Other Study ID Numbers: 2012P000957A; 1R01HL102321-01A1 ( U.S. NIH Grant/Contract )
• First Posted: November 20, 2012
• Last Update Posted: July 11, 2019
• Last Verified: July 2019

Keywords provided by David Andrew Wellman, Brigham and Women's Hospital:

Obstructive Sleep Apnea; Pathophysiology

Additional relevant MeSH terms:

Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Anesthetics; Central Nervous System Depressants; Physiological Effects of Drugs