Rescue Pharmacotherapy for OSA

Obstructive Sleep Apnea Clinical Trial

— RescOSA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05293600
• Other study ID #: 2022p000430
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: July 1, 2023
• Est. completion date: October 30, 2026

Study information

• Verified date: June 2024
• Source: Brigham and Women's Hospital
• Contact: David Andrew Wellman, MD
• Phone: 5089827401
• Email: awellman[@]bwh.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: October 30, 2026
• Est. primary completion date: October 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Obstructive Sleep Apnea
• Sleep Apnea, Obstructive

Intervention

Drug:
• Placebo
Placebo capsule 30 min before bedtime
• Acetazolamide
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.
• Trazodone
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 eszopiclone
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.

Locations

Country	Name	City	State
United States	Sleep Disorders Research Program Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Brigham and Women's Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	1 night
Secondary	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.	1 night
Secondary	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.	1 night