What is the mechanism of action of this treatment?

Common treatments for Obstructive Sleep Apnea (OSA) include pharmacological agents like Atomoxetine and Oxybutynin. Atomoxetine, a selective norepinephrine reuptake inhibitor, increases norepinephrine levels, which can enhance upper airway muscle tone and reduce airway collapse during sleep. Oxybutynin, an anticholinergic agent, reduces muscle spasms and airway resistance through its antimuscarinic effects. These mechanisms are crucial for OSA patients as they offer a pharmacological means to reduce OSA severity by improving airway patency, providing an alternative or complement to traditional treatments like CPAP.

What side effects are associated with this type of intervention?

Common treatments for Obstructive Sleep Apnea (OSA) include Continuous Positive Airway Pressure (CPAP) therapy, oral appliances, and surgical interventions. CPAP therapy can cause side effects such as nasal congestion, dry mouth, and skin irritation. Oral appliances may lead to jaw discomfort and dental issues. Surgical options carry risks of infection and pain. For treatments similar to Atomoxetine-plus-oxybutynin therapy, Atomoxetine (a Selective Norepinephrine Reuptake Inhibitor) can cause side effects like insomnia, dry mouth, and increased heart rate. Oxybutynin (an Anticholinergic Agent) may lead to dry mouth, constipation, and blurred vision. Combining these medications may increase the likelihood of experiencing these side effects.

What prior FDA approvals exist?

As of now, there are no FDA-approved treatments for Obstructive Sleep Apnea (OSA) that specifically combine a Selective Norepinephrine Reuptake Inhibitor (SNRI) like Atomoxetine and an anticholinergic agent like Oxybutynin. The current standard treatments for OSA primarily include continuous positive airway pressure (CPAP) therapy, oral appliances, and surgical interventions. Pharmacological treatments for OSA are still under investigation, with the combination of Atomoxetine and Oxybutynin showing promise in recent clinical trials but not yet approved by the FDA.

What other types of research exist?

Promising novel alternatives to Atomoxetine-plus-oxybutynin therapy for OSA patients include hypoglossal nerve stimulation, which has shown efficacy in reducing OSA severity by stimulating the muscles that keep the airway open, and the use of positive airway pressure (PAP) devices with advanced algorithms for personalized therapy. Additionally, pharmacological agents targeting the orexin system, such as dual orexin receptor antagonists, are being explored for their potential to improve sleep quality and reduce OSA symptoms.

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Atomoxetine + Oxybutynin for Sleep Apnea

Phase 1 & 2

Recruiting

Led By Scott A Sands, PhD

Research Sponsored by Brigham and Women's Hospital

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Suspected or diagnosed OSA

Be older than 18 years old

Must not have

Other sleep disorders: periodic limb movements, narcolepsy, or parasomnias

Contraindications for atomoxetine and oxybutynin, including: hypersensitivity to atomoxetine or oxybutynin (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, moderate-to-severe hypertension (SBP>180 mmHg or DBP>110 mmHg measured at baseline; average of evening and morning measures*), 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, Claustrophobia

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 3 days

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of two medications, atomoxetine and oxybutynin, to reduce sleep apnea severity. Previous studies have shown that the combination of these medications can significantly reduce obstructive sleep apnea severity by increasing upper airway muscle activity during sleep. It focuses on patients with specific traits that might make them more likely to respond well to this treatment. The medications help keep the airway open by affecting muscle control and reducing collapsibility.

Who is the study for?

This trial is for people with suspected or diagnosed obstructive sleep apnea who have recent drug-induced sleep endoscopy results. It's not for those with uncontrolled medical conditions, other major respiratory disorders, using certain medications like hypnotics or SSRIs, pregnant or nursing women, and individuals with a range of specific health issues such as severe hypertension, heart failure, liver/kidney disease.

What is being tested?

The study tests whether Atomoxetine-plus-oxybutynin therapy (AtoOxy) effectively reduces the severity of obstructive sleep apnea in patients. Researchers will identify which patients benefit most based on traits measured during initial sleep studies.

What are the potential side effects?

Potential side effects from Atomoxetine and Oxybutynin may include allergic reactions like angioedema or urticaria, mood changes including mania or depression in young adults under 24 years old, constipation, difficulty urinating due to urinary retention, seizures in those predisposed to them.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have or might have sleep apnea.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a sleep disorder like restless legs, sleep attacks, or unusual behaviors during sleep.

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I don't have allergies to atomoxetine or oxybutynin, heart, kidney, liver issues, or certain mental health conditions.

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I am not taking medications that affect my breathing.

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I am currently taking SNRIs/SSRIs or anticholinergic medications.

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I do not have any uncontrolled medical conditions.

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I do not have major neurological disorders, heart failure, or other unstable conditions.

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I have a lung condition that is not sleep-related and causes low oxygen levels.

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I am currently taking sleep medications.

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I am currently taking the medication being studied.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 3 days

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~3 days

This trial's timeline: 3 weeks for screening, Varies for treatment, and 3 days for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Apnea

Secondary study objectives

Arousal Index

Hypoxia

Side effects data

From 2008 Phase 4 trial • 57 Patients • NCT00224016

18%

Infection

18%

Headache

15%

Urinary tract infection

15%

Fever

13%

Pharyngitis

13%

Rash

13%

Vomiting

10%

Pain

10%

Constipation

Pain abdominal

Pruritis

Rhinitis

Diarrhea

Pain back

VP shunt malfunction

Skin ulcer

Gastritis

Knee wound dehiscence

Worsening dehydration

Tethered cord

100%

80%

60%

40%

20%

Study treatment Arm

Oxybutynin TDS

Oral Oxybutynin

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: AtoOxy Predicted RespondersExperimental Treatment2 Interventions

Participants will take Atomoxetine (80mg) and Oxybutynin (5mg) before bedtime for 3 nights. Half doses will be given on the first night.

Group II: AtoOxy Predicted NonrespondersExperimental Treatment2 Interventions

Participants will take Atomoxetine (80mg) and Oxybutynin (5mg) before bedtime for 3 nights. Half doses will be given on the first night.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Atomoxetine

2010

Completed Phase 4

~431790

Oxybutynin

2015

Completed Phase 4

~2750

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Obstructive Sleep Apnea (OSA) include pharmacological agents like Atomoxetine and Oxybutynin. Atomoxetine, a selective norepinephrine reuptake inhibitor, increases norepinephrine levels, which can enhance upper airway muscle tone and reduce airway collapse during sleep. Oxybutynin, an anticholinergic agent, reduces muscle spasms and airway resistance through its antimuscarinic effects. These mechanisms are crucial for OSA patients as they offer a pharmacological means to reduce OSA severity by improving airway patency, providing an alternative or complement to traditional treatments like CPAP.

The norepinephrine reuptake inhibitor reboxetine alone reduces obstructive sleep apnea severity: a double blind, placebo controlled, randomized, cross-over trial.The pharmacotherapeutic management of obstructive sleep apnea.The Combination of Atomoxetine and Oxybutynin Greatly Reduces Obstructive Sleep Apnea Severity. A Randomized, Placebo-controlled, Double-Blind Crossover Trial.