Obstructive Sleep ApneaPhase 1/2RescOSANCT05293600
Rescue Pharmacotherapy for OSA
A Phase 1/2 study testing Acetazolamide, Trazodone and Atomoxetine and eszopiclone in people with Obstructive Sleep Apnea, run by Brigham and Women's Hospital at 1 site in United States.
Trial summary
Persistent obstructive sleep apnea (OSA) is common in people treated with mandibular advancement device (MAD) or hypoglossal nerve stimulation (HGNS). For most patients, these treatments are the last line of defense. If MAD or HGNS do not work, then patients are left to suffer the consequences of undertreated OSA. Read more about this study
- Who is it for?
- Ages 21 to 70 years
- Conditions the study is for
- Obstructive Sleep Apnea
- What is being tested?
- Acetazolamide, Trazodone and Atomoxetine and eszopiclone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2023to 30 Oct 2026
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Individuals who have failed MAD or HGNS therapy, defined as a residual AHI ≥ 15 events/hr on MAD or HGNS therapy.
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Sleep Disorders Research Program Brigham and Women's Hospital
Boston, Massachusetts, 02115
Ludovico Messineo, 8572726188, lmessineo@bwh.harvard.edu
About this study
Official title: Treating Residual OSA With Endotype-directed Pharmacotherapy (Aim 3)
Persistent obstructive sleep apnea (OSA) is common in people treated with mandibular advancement device (MAD) or hypoglossal nerve stimulation (HGNS). For most patients, these treatments are the last line of defense. If MAD or HGNS do not work, then patients are left to suffer the consequences of undertreated OSA. In this study, the investigators want to test the addition of a drug treatment to their regimen. Endotypes will be targeted pharmacologically with one of the following drugs: acetazolamide for a high loop gain, atomoxetine-plus-eszopiclone for poor pharyngeal muscle compensation, or trazodone for a low arousal threshold.
This aim is expected to provide treatment strategies for rescuing non-responders to MAD or HGNS therapy.
- Conditions
- Obstructive Sleep Apnea
- Being tested
- Placebo, Acetazolamide, Trazodone, Atomoxetine and eszopiclone
- Medical subject headings
- Sleep Apnea, Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Placebo capsule 30 min before bedtime
AcetazolamideDrug
The intervention drug will be determined based on altered endotype and administered 30 min before bedtime. Patients will only take one drug of this intervention, which will be subsequently compared to placebo. Patients with increased loop gain will be given Acetazolamide 500 mg.
TrazodoneDrug
The intervention drug will be determined based on altered endotype and administered 30 min before bedtime. Patients will only take one drug of this intervention, which will be subsequently compared to placebo. Patients with decreased arousal threshold will be given Trazodone 100 mg.
Atomoxetine and eszopicloneDrug
The intervention drug will be determined based on altered endotype and administered 30 min before bedtime. Patients will only take one drug of this intervention, which will be subsequently compared to placebo. Patients with decreased muscle responsiveness will be given Atomoxetine and Eszopiclone 80 + 3 mg.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | This is a two arm study. Patients will receive only one of the following drugs based on their altered sleep apnea trait. Patients with decreased arousal threshold will undergo treatment with placebo or Trazodone 100 mg in random order (one pill before 30 minutes before bedtime), patients with decreased pharyngeal muscle responsiveness will undergo treatment with placebo or Atomoxetine 80 mg + Eszopiclone 3 mg in random order (one pill before 30 minutes before bedtime), patients with increased loop gain will undergo treatment with placebo or Acetazolamide 500 mg in random order (one pill before 30 minutes before bedtime). Receives: Drug: Placebo |
| Interventional arm | Active comparator | This is a two arm study. Patients will receive only one of the following drugs based on their altered sleep apnea trait. Patients with decreased arousal threshold will undergo treatment with placebo or Trazodone 100 mg in random order (one pill before 30 minutes before bedtime), patients with decreased pharyngeal muscle responsiveness will undergo treatment with placebo or Atomoxetine 80 mg + Eszopiclone 3 mg in random order (one pill before 30 minutes before bedtime), patients with increased loop gain will undergo treatment with placebo or Acetazolamide 500 mg in random order (one pill before 30 minutes before bedtime). Receives: Drug: Acetazolamide; Drug: Trazodone; Drug: Atomoxetine and eszopiclone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Apnea Hypopnea Index (AHI, Events/Hour of Sleep)
Based on previous studies the investigators anticipate that the interventional arm will reduce AHI through a positive effect on the abnormal endotype.
Measured: 1 night
Secondary outcomes (2)
Nadir oxygen saturation during sleep (LSpO2, %)
Based on previous studies the investigators anticipate that the interventional arm will reduce LSpO2 through a positive effect on the abnormal endotype.
Measured: 1 night
Arousal Index (AI, Events/Hours of Sleep)
Based on previous studies the investigators anticipate that the interventional arm will reduce AI through inducing less fragmented sleep, which will be driven by a positive effect on the abnormal endotype.
Measured: 1 night
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2022
- Study start1 Jul 2023
- Primary completion30 Oct 2026 (estimated)
- Study completion30 Oct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Obstructive Sleep ApneaStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David Andrew Wellman, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05293600
- Sponsor's protocol ID
- 2022p000430
- Acronym
- RescOSA
- Status last verified
- Jul 2026
- First submitted
- 23 Feb 2022
- Last updated
- 15 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treating Residual OSA With Endotype-directed Pharmacotherapy (Aim 3)
- ClinicalTrials.gov ID
- NCT05293600
- Acronym / sponsor ID
- RescOSA / 2022p000430
- Conditions
- Obstructive Sleep Apnea
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- 1 Jul 2023 (actual)
- Primary completion
- 30 Oct 2026 (estimated)
- Study completion
- 30 Oct 2026 (estimated)
- First posted
- 24 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Persistent obstructive sleep apnea (OSA) is common in people treated with mandibular advancement device (MAD) or hypoglossal nerve stimulation (HGNS). For most patients, these treatments are the last line of defense. If MAD or HGNS do not work, then patients are left to suffer the consequences of undertreated OSA. In this study, the investigators want to test the addition of a drug treatment to their regimen. Endotypes will be targeted pharmacologically with one of the following drugs: acetazolamide for a high loop gain, atomoxetine-plus-eszopiclone for poor pharyngeal muscle compensation, or trazodone for a low arousal threshold.
This aim is expected to provide treatment strategies for rescuing non-responders to MAD or HGNS therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboThis is a two arm study. Patients will receive only one of the following drugs based on their altered sleep apnea trait. Patients with decreased arousal threshold will undergo treatment with placebo or Trazodone 100 mg in random order (one pill before 30 minutes before bedtime), patients with decreased pharyngeal muscle responsiveness will undergo treatment with placebo or Atomoxetine 80 mg + Eszopiclone 3 mg in random order (one pill before 30 minutes before bedtime), patients with increased loop gain will undergo treatment with placebo or Acetazolamide 500 mg in random order (one pill before 30 minutes before bedtime). |
| Interventional arm | Active comparator | Drug: Acetazolamide, Drug: Trazodone, Drug: Atomoxetine and eszopicloneThis is a two arm study. Patients will receive only one of the following drugs based on their altered sleep apnea trait. Patients with decreased arousal threshold will undergo treatment with placebo or Trazodone 100 mg in random order (one pill before 30 minutes before bedtime), patients with decreased pharyngeal muscle responsiveness will undergo treatment with placebo or Atomoxetine 80 mg + Eszopiclone 3 mg in random order (one pill before 30 minutes before bedtime), patients with increased loop gain will undergo treatment with placebo or Acetazolamide 500 mg in random order (one pill before 30 minutes before bedtime). |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Individuals who have failed MAD or HGNS therapy, defined as a residual AHI ≥ 15 events/hr on MAD or HGNS therapy.
Key exclusion criteria (51 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboPlacebo capsule 30 min before bedtime | Drug | Placebo |
| AcetazolamideThe intervention drug will be determined based on altered endotype and administered 30 min before bedtime. Patients will only take one drug of this intervention, which will be subsequently compared to placebo. Patients with increased loop gain will be given Acetazolamide 500 mg. | Drug | Interventional arm |
| TrazodoneThe intervention drug will be determined based on altered endotype and administered 30 min before bedtime. Patients will only take one drug of this intervention, which will be subsequently compared to placebo. Patients with decreased arousal threshold will be given Trazodone 100 mg. | Drug | Interventional arm |
| Atomoxetine and eszopicloneThe intervention drug will be determined based on altered endotype and administered 30 min before bedtime. Patients will only take one drug of this intervention, which will be subsequently compared to placebo. Patients with decreased muscle responsiveness will be given Atomoxetine and Eszopiclone 80 + 3 mg. | Drug | Interventional arm |
Primary outcome
Apnea Hypopnea Index (AHI, Events/Hour of Sleep)
Time frame: 1 night
Based on previous studies the investigators anticipate that the interventional arm will reduce AHI through a positive effect on the abnormal endotype.
2 secondary outcomes
Nadir oxygen saturation during sleep (LSpO2, %)
Time frame: 1 night
Arousal Index (AI, Events/Hours of Sleep)
Time frame: 1 night
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2026.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Acetazolamide, Trazodone and Atomoxetine and eszopiclone in people with Obstructive Sleep Apnea, run by Brigham and Women's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 51 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact David Andrew Wellman, MD (5089827401, awellman@bwh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Apnea Hypopnea Index (AHI, Events/Hour of Sleep) (time frame: 1 night). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2026.