Drug treatment for patients with obstructive sleep apnea who didn't respond to other therapies

Treating Residual OSA With Endotype-directed Pharmacotherapy (Aim 3)

Phase1; Phase2 Interventional Brigham and Women's Hospital · NCT05293600

This study is testing if adding certain medications can help people with obstructive sleep apnea who haven't improved with other treatments feel better.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment70 (estimated)
Ages21 Years to 70 Years
SexAll
SponsorBrigham and Women's Hospital Academic / other
Locations1 site (Boston, Massachusetts)
Trial IDNCT05293600 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the effectiveness of adding pharmacotherapy to patients with obstructive sleep apnea (OSA) who have not responded to mandibular advancement devices (MAD) or hypoglossal nerve stimulation (HGNS). Participants will receive one of several drug treatments, including acetazolamide, trazodone, or a combination of atomoxetine and eszopiclone, based on their specific OSA endotype. The goal is to identify effective rescue strategies for those who continue to experience symptoms despite existing therapies.

Who should consider this trial

Good fit: Ideal candidates are individuals who have failed MAD or HGNS therapy and have a residual apnea-hypopnea index (AHI) of 15 events/hour or more.

Not a fit: Patients with central sleep apnea, other significant sleep disorders, or unstable major medical conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide new treatment options for patients with persistent obstructive sleep apnea who have not benefited from standard therapies.

How similar studies have performed: While the approach of combining pharmacotherapy with existing treatments is innovative, similar studies have shown promise in addressing treatment-resistant cases of obstructive sleep apnea.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* Individuals who have failed MAD or HGNS therapy, defined as a residual AHI ≥ 15 events/hr on MAD or HGNS therapy.

Exclusion Criteria:

* Sleep disordered breathing or respiratory disorders other than obstructive sleep apnea:

central sleep apnea (\>50% of respiratory events scored as central), chronic hypoventilation/hypoxemia (awake SaO2 \< 92% by oximetry) due to chronic obstructive pulmonary disease or other respiratory conditions.

* Other sleep disorders: periodic limb movements (periodic limb movement index \> 20/hr), narcolepsy, or parasomnias.
* Any unstable major medical condition.
* Medications expected to stimulate or depress respiration (including opioids, barbiturates, benzodiazepines, doxapram, almitrine, theophylline, 4-hydroxybutanoic acid).
* Use of SSRIs/SNRIs.
* Contraindications for atomoxetine, including:
* pheochromocytoma
* use of monoamine oxidase inhibitors
* benign prostatic hypertrophy, urinary retention
* untreated narrow angle glaucoma
* bipolar disorder, mania, psychosis
* clinically significant constipation, gastric retention
* pre-existing seizure disorders
* clinically-significant kidney disorders
* clinically-significant liver disorders
* clinically-significant cardiovascular conditions
* severe hypertension (SBP\>180 mmHg or DBP\>110 mmHg measured at baseline)
* cardiomyopathy (LVEF\<50%) or heart failure
* advanced atherosclerosi
* history of cerebrovascular events
* history of cardiac arrhythmias e.g., atrial fibrillation, QT prolongation
* other serious cardiac conditions that would raise the consequences of an increase in blood pressure or heart rate
* myasthenia gravis
* pregnancy/breast-feeding
* Contraindications for eszopiclone, including:
* Hypersensitivity to eszopiclone
* Chronic Obstructive Pulmonary Disease (COPD)
* Pregnancy
* Breast feeding
* Liver disease
* Contraindications for acetazolamide, including:
* Hyperchloremic acidosis
* Hypokalemia
* Hyponatremia
* Adrenal insufficiency
* Impaired kidney function
* Hypersensitivity to acetazolamide or other sulfonamides.
* Marked liver disease or impairment of liver function, including cirrhosis.
* Contraindications for trazodone, including:
* suicidal ideation
* bipolar disorder, mania
* use of monoamine oxidase inhibitors
* coronary artery disease
* cardiac arrhythmias
* QT prolongation
* hepatic disease
* renal failure or impairment
* closed angle glaucoma
* priapism
* pregnancy/breast-feeding

Where this trial is running

Boston, Massachusetts

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Obstructive Sleep Apnea
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.