A Novel Pharmacological Therapy for Obstructive Sleep Apnea

NCT03919955 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2019P000666R01HL146697
• Study Type: interventional
• Target: 117
• Locations: 1 country
• Sites: 1

Brief 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?

Conditions

Sleep Apnea

Outcome Measures

Primary Outcomes (1)

• Apnea-hypopnea Index [AHI]

  Apneas and hypopneas per hour (3% desat and/or arousal), % change from baseline

  one month

Secondary Outcomes (5)

• Hypoxic Burden

  one month

• Arousal Index

  one month

• Epworth Sleepiness Scale

  one month

• Functional Outcomes of Sleep Questionnaire, Short Form

  one month

• Sleep Apnea Quality of Life Index, Short Form

  one month

Study Arms (2)

Sequence A: Atomoxetine and Oxybutynin, then Placebo

EXPERIMENTAL

Sequence A: Atomoxetine and Oxybutynin, then Placebo

Drug: Atomoxetine; Drug: Oxybutynin; Drug: Placebo

Sequence B: Placebo, then Atomoxetine and Oxybutynin

EXPERIMENTAL

Sequence B: Placebo, then Atomoxetine and Oxybutynin.

Drug: Atomoxetine; Drug: Oxybutynin; Drug: Placebo

Interventions

Atomoxetine DRUG

Atomoxetine 80 mg, per mouth, before bed. Participants will take the intervention nightly for one month. Half doses will be given on the first three nights.

Also known as: Strattera

Sequence A: Atomoxetine and Oxybutynin, then Placebo; Sequence B: Placebo, then Atomoxetine and Oxybutynin

Oxybutynin DRUG

Oxybutynin 5 mg, per mouth, before bed. Participants will take the intervention nightly for one month. Half doses will be given on the first three nights.

Also known as: Ditropan

Sequence A: Atomoxetine and Oxybutynin, then Placebo; Sequence B: Placebo, then Atomoxetine and Oxybutynin

Placebo DRUG

Placebo, per mouth, before bed.Participants will take the intervention nightly for one month. Half doses will be given on the first three nights.

Sequence A: Atomoxetine and Oxybutynin, then Placebo; Sequence B: Placebo, then Atomoxetine and Oxybutynin

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ages 21-70 years
• Diagnosed OSA or clinically-suspected OSA
• Not using CPAP (\>1 month).

You may not qualify if:

• 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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Sleep Apnea Syndromes

Interventions

Atomoxetine Hydrochloride; oxybutynin

Condition Hierarchy (Ancestors)

Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Scott Sands
• Organization: Brigham and Women's Hospital

scottysands@gmail.com

8579280341

Study Officials

• Scott A Sands, PhD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: April 16, 2019
• First Posted: April 18, 2019
• Study Start: September 3, 2019
• Primary Completion: September 7, 2023
• Study Completion: September 7, 2023
• Last Updated: December 23, 2025
• Results First Posted: December 23, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Immediately after publication. No end date.
• Access Criteria: 1-page proposals should be directed to Dr. Scott Sands (sasands@bwh.harvard.edu). To gain access, requestors will be asked to sign a data use agreement.

Locations

US (1)