A Novel Pharmacological Therapy for Obstructive Sleep Apnea

• Status: Recruiting
• Trial end date: 2024-05-01
• Target enrollment: 0
• Participant gender: All

Summary

A pharmacological, non-mechanical therapy for OSA that is efficacious and tolerable remains elusive. Here the investigators study the effect on sleep apnea severity of a combination of pharmacological agents (atomoxetine and oxybutynin, "AtoOxy") over a 1 month period of time. The current study will answer the following questions: Does ongoing, repeated-dose administration of atomoxetine-plus-oxybutynin (referred to as "AtoOxy") improve OSA severity, and do patients exhibit signs of symptomatic relief? Most importantly, which phenotypic subgroup of patients preferentially benefit from this intervention?

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Brigham and Women's Hospital
• Treatments: Atomoxetine Hydrochloride; Mandelic Acids; Oxybutynin

Criteria

Inclusion criteria:

• Ages 21-70 years

• Diagnosed OSA or clinically-suspected OSA

• Not using CPAP (>1 month).

Exclusion criteria:

• Any uncontrolled medical condition

• Current use of the medications under investigation

• Use of medications expected to stimulate or depress respiration (including opioids, barbiturates, doxapram, almitrine, theophylline, 4-hydroxybutanoic acid).

• Current use of hypnotic medications (trazodone, eszopiclone, benzodiazepines).

• Current use of SNRIs/SSRIs or anticholinergic medications.

• Conditions likely to affect obstructive sleep apnea physiology: neuromuscular disease or other major neurological disorder, heart failure (also below), or any other unstable major medical condition.

• Respiratory disorders other than sleep disordered breathing:

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 arousal index > 10/hr), narcolepsy, or parasomnias.

• Contraindications for atomoxetine and oxybutynin, including:

• hypersensitivity to study drugs (angioedema or urticaria)

• pheochromocytoma

• use of monoamine oxidase inhibitors

• benign prostatic hypertrophy, urinary retention

• untreated narrow angle glaucoma

• bipolar disorder, mania, psychosis

• history of major depressive disorder (age<24).

• history of attempted suicide or suicidal ideation within one year prior to screening

• clinically significant constipation, gastric retention

• pre-existing seizure disorders

• clinically-significant kidney disorders (eGFR<60 ml/min/1.73m2)

• 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 atherosclerosis

• 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

• Allergy to lidocaine (Aim 2 only)

• Claustrophobia

• Pregnancy or nursing