RescOSA: Rescue Pharmacotherapy for OSA

Sponsor
Brigham and Women's Hospital (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05293600
Collaborator
(none)
70
1
2
22
3.2

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
70 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Treating Residual OSA With Endotype-directed Pharmacotherapy (Aim 3)
Anticipated Study Start Date :
Sep 1, 2022
Anticipated Primary Completion Date :
Dec 1, 2023
Anticipated Study Completion Date :
Jul 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Placebo

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).

Drug: Placebo
Placebo capsule 30 min before bedtime

Active Comparator: Interventional arm

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).

Drug: 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.

Drug: 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.

Drug: 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.

Outcome Measures

Primary Outcome Measures

  1. Apnea Hypopnea Index (AHI, Events/Hour of Sleep) [1 night]

    Based on previous studies the investigators anticipate that the interventional arm will reduce AHI through a positive effect on the abnormal endotype.

Secondary Outcome Measures

  1. Nadir oxygen saturation during sleep (LSpO2, %) [1 night]

    Based on previous studies the investigators anticipate that the interventional arm will reduce LSpO2 through a positive effect on the abnormal endotype.

  2. Arousal Index (AI, Events/Hours of Sleep) [1 night]

    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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
21 Years to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Sleep Disorders Research Program Brigham and Women's Hospital Boston Massachusetts United States 02115

Sponsors and Collaborators

  • Brigham and Women's Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
David Andrew Wellman, Associate Professor of Medicine, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT05293600
Other Study ID Numbers:
  • 2022p000430
First Posted:
Mar 24, 2022
Last Update Posted:
Jul 20, 2022
Last Verified:
Jul 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 20, 2022