Medications for Obstructive Sleep Apnea In Children With Down Syndrome

NCT04115878 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 1908864846R61HL151254
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double blind, cross-over study of the combination of atomoxetine and oxybutynin (ato-oxy) in children with DS and OSA documented by polysomnography (PSG). Participants will receive high dose ato-oxy for four weeks as well as low dose ato-oxy for four weeks in random order. During the high dose ato-oxy period, participants will take 5 mg oxybutynin and 0.5mg/kg/day (max 40 mg) atomoxetine nightly for one week. Atomoxetine dose will then be increased to 1.2 mg/kg/day (max 80 mg). During the low dose ato-oxy period, participants will take 5 mg oxybutynin and 0.5mg/kg/day (max 40 mg) atomoxetine. Dosing of the study treatment will occur approximately 30 minutes prior to bedtime. Participants who withdraw from the study will not be replaced. Study participants will undergo eligibility screening that will include an initial screening to determine whether non- PSG enrollment criteria are met, followed by a 1 night in-lab PSG and health-related quality of life assessment for participants who qualify based on non-PSG criteria. For participants who are eligible and enroll in the study, the screening PSG night will serve as the baseline measure for apnea hypopnea index (AHI) and other PSG endpoints. On the final night of dosing for both high dose ato-oxy and low-dose ato-oxy, participants will return for inpatient PSG and health-related quality of life assessment. The primary efficacy endpoint is the change in obstructive AHI from baseline (high dose ato-oxy vs. low dose ato-oxy).

Conditions

Obstructive Sleep Apnea; Down Syndrome

Keywords

atomoxetine; oxybutynin

Outcome Measures

Primary Outcomes (1)

• Obstructive Apnea-hypopnea Index (oAHI)

  change in number of obstructive apneas and hypopneas per hour on polysomnography from baseline

  four weeks

Secondary Outcomes (2)

• Obstructive Sleep Apnea-18 Score (OSA-18)

  four weeks

• Arousal Index

  four weeks

Other Outcomes (5)

• Pediatric Quality of Life Inventory (PedsQL) Total Score

  four weeks

• Caregiver Global Impression of Change

  four weeks

• N1 Sleep Percentage

  four weeks

Study Arms (2)

High dose ato-oxy

ACTIVE COMPARATOR

Drug: Atomoxetine and oxybutynin (ato-oxy)

Low dose ato-oxy

ACTIVE COMPARATOR

Drug: Atomoxetine and oxybutynin (ato-oxy)

Interventions

Atomoxetine and oxybutynin (ato-oxy) DRUG

Low dose ato-oxy will include 0.5 mg/kg/day of atomoxetine (max 40 mg) in combination with 5 mg oxybutynin High dose ato-oxy will include 1.2 mg/kg/day atomoxetine (max 80 mg) and 5 mg oxybutynin

High dose ato-oxy; Low dose ato-oxy

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male or female participants between 6 to 17 years of age, inclusive, at the Screening Visit. Enrollment will be stratified to ensure equal representation of children age 6-12 and age 13-17. No more than 14 subjects will be randomized for each age group.
• Known diagnosis of Down syndrome (trisomy 21, but not translocation or mosaicism)

You may not qualify if:

• Hypoxemia independent of respiratory events on polysomnography (≥5 minutes with oxygen saturation \<90%)
• Presence of central sleep apnea on polysomnography (central AHI ≥ 5)
• Currently using and adherent to PAP therapy (\>4 hours per night for 70% of nights in the past 30 days based on device download or parent report)
• MAO inhibitor use
• Urinary retention
• Prematurity \< 37 weeks estimated gestational age
• Seizure disorder
• Untreated or inadequately treated hypothyroidism
• Significant traumatic brain injury
• Congenital heart disease and not cleared to participate by the patient's cardiologist
• History of current, untreated depression
• History of liver disease
• + or greater tonsillar hypertrophy.

Sponsors & Collaborators

• University of Arizona: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Arizona

Tucson, Arizona, 85721, United States

Location

Related Publications (1)

• Combs D, Edgin J, Hsu CH, Bottrill K, Van Vorce H, Gerken B, Matloff D, La Rue S, Parthasarathy S. The combination of atomoxetine and oxybutynin for the treatment of obstructive sleep apnea in children with Down syndrome. J Clin Sleep Med. 2023 Dec 1;19(12):2065-2073. doi: 10.5664/jcsm.10764.

  PMID: 37555595 DERIVED

MeSH Terms

Conditions

Sleep Apnea, Obstructive; Down Syndrome

Interventions

Atomoxetine Hydrochloride; oxybutynin

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Daniel Combs, MD
• Organization: University of Arizona

combs89@arizona.edu

520-626-7780

Study Officials

• Daniel Combs, MD

  University of Arizona

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• 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: Assistant Professor of Pediatrics

Study Record Dates

• First Submitted: October 2, 2019
• First Posted: October 4, 2019
• Study Start: October 21, 2020
• Primary Completion: December 30, 2022
• Study Completion: December 30, 2022
• Last Updated: August 19, 2025
• Results First Posted: August 19, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

US (1)