# Predicting response to non-PAP therapies in OSA using PSG-derived endotypes

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $816,208

## Abstract

ABSTRACT
 Obstructive Sleep Apnea (OSA) is a common disorder with serious health consequences that often
remains undertreated due to few therapeutic options beyond continuous positive airway pressure (CPAP).
Alternative treatments are available, such as mandibular advancement devices (MADs) and hypoglossal nerve
stimulation (HGNS). However, these treatments are not always effective, and the predictors of success are
poorly understood or difficult to obtain. Furthermore, patients who fail these therapies are often left untreated
and therefore susceptible to the clinical consequences of OSA.
 In the previous grant period, we developed methods for estimating the pathophysiological endotypes of
OSA (pharyngeal collapsibility, loop gain, pharyngeal muscle compensation, and arousal threshold), as well as
the primary site of airway collapse (palate, tongue, lateral walls, epiglottis), from the clinical polysomnogram
(PSG). The objective of this grant is to apply these methods to 1) find predictors of MAD and HGNS response
and 2) test endotype-specific pharmacotherapies in MAD and HGNS non-responders. Our hypothesis is that
these endotypes/sites of collapse, as determined from the PSG, are important predictors of MAD and HGNS
response. We also hypothesize that the addition of a drug targeting an abnormal endotype, e.g., high loop
gain, can be used to more effectively treat MAD and HGNS non-responders.
 In the first two aims, the physiological endotypes and sites of collapse will be determined from the
clinical PSG using the methods developed in the previous grant cycle. Patients will then undergo MAD (Aim 1)
or HGNS (Aim 2) therapy. A follow-up PSG will be performed to evaluate the success of treatment. Using
multivariable logistic regression, the significant physiological predictors of success will be determined.
 In Aim 3, the patients who fail MAD or HGNS in the previous aims, approximately one-third of
individuals, will be treated with a drug targeting the most abnormal endotype (acetazolamide for high loop gain,
atomoxetine-plus-oxybutynin for poor pharyngeal muscle compensation, or trazodone for low arousal
threshold). Recent evidence suggests that these drugs can manipulate the endotypes. The drug will be
administered concurrently with MAD or HGNS treatment (combination therapy).
 Aims 1 and 2 are expected to find the important physiological predictors of MAD and HGNS response,
respectively, using novel metrics derived from the clinical PSG. Aim 3 is expected to provide proof-of-principle
for a pharmacologic approach to treating MAD and HGNS failures, patients who otherwise have limited
treatment options. Ultimately, these studies have the potential to improve patient selection for non-CPAP
alternatives and broaden the treatment options for OSA.

## Key facts

- **NIH application ID:** 10440108
- **Project number:** 2R01HL102321-10A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** DAVID ANDREW WELLMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $816,208
- **Award type:** 2
- **Project period:** 2022-09-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10440108

## Citation

> US National Institutes of Health, RePORTER application 10440108, Predicting response to non-PAP therapies in OSA using PSG-derived endotypes (2R01HL102321-10A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10440108. Licensed CC0.

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