Identifying Sleep Apnea Patients That Best Respond to Atomoxetine Plus Oxybutynin Therapy

NCT ID: NCT05550246

Last Updated: 2023-10-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-05
• Study Completion Date: 2024-12-31

Brief Summary

Atomoxetine-plus-oxybutynin therapy (AtoOxy) has been shown to substantially reduce obstructive sleep apnea severity (OSA) in about half of patients. Here, the investigators will study which patients respond meaningfully to therapy using pathophysiological traits measured at baseline sleep studies.

Detailed Description

The primary goal of the current study is to test the central hypothesis that therapeutic efficacy of AtoOxy depends on underlying patient pathophysiology.

Aim 1 - Advanced analysis of clinical polysomnography will be used to estimate the OSA traits and classify patients as 'predicted responders' or 'predicted nonresponders'. Investigators will prospectively test whether AtoOxy efficacy is greater in predicted responders.

Aim 2 - Pooling preliminary and prospective data, investigators will test the hypotheses that the following pathophysiological traits are associated with, and therefore predict, greater efficacy: less-severe upper airway collapsibility (less improvement needed to re-establish airflow), lower loop gain (less severe ventilatory control instability), higher arousal threshold (greater scope for muscle activation without arousal), and greater upper airway muscle compensation (functional muscle reflex apparatus).

Aim 3 - Investigators will test the hypothesis that treatment efficacy will be greater in patients with tongue-related upper airway obstruction per previous drug-induced sleep endoscopy results (anterior-posterior collapse patterns).

Conditions

Obstructive Sleep Apnea

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AtoOxy Predicted Responders

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

Group Type: EXPERIMENTAL

Atomoxetine

Intervention Type: DRUG

Treatment given for 3 nights

Oxybutynin

Intervention Type: DRUG

Treatment given for 3 nights

AtoOxy Predicted Nonresponders

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

Group Type: EXPERIMENTAL

Atomoxetine

Intervention Type: DRUG

Treatment given for 3 nights

Oxybutynin

Intervention Type: DRUG

Treatment given for 3 nights

Interventions

Atomoxetine

Treatment given for 3 nights

Intervention Type: DRUG

Oxybutynin

Treatment given for 3 nights

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Suspected or diagnosed OSA
• Recent drug induced sleep endoscopy results available (performed as part of routine clinical care).

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, 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
• Pregnancy or nursing

n.b. Development of new hypertension that is recognized on the final day of study medications during outcomes collection will not be used as stopping criteria for discontinuing outcomes collection.

Participants that are sexually active and able to become pregnant must agree to use birth control for the entire study.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Scott Aaron Sands

Assistant Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Scott A Sands, PhD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Scott A Sands, PhD

Role: CONTACT

sasands@bwh.harvard.edu

617-278-0911

Laura K Gell, PhD

Role: CONTACT

lgell@bwh.harvard.edu

617-525-9086

Facility Contacts

Scott A Sands, PhD

Role: primary

sasands@bwh.harvard.edu

857-928-0341

Other Identifiers

2022P001544

Identifier Type: -

Identifier Source: org_study_id