Medications for Obstructive Sleep Apnea to Improve Cognition in Children With Down Syndrome (MOSAIC)

This is an open-label study of the combination of atomoxetine and oxybutynin (ato-oxy) in children with Down syndrome and obstructive sleep apnea (OSA) documented by polysomnography (PSG). Participants will receive ato-oxy for 6 months. Ato-oxy dose will be 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 (HRQOL) and cognitive 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 ato-oxy participants will return for inpatient PSG and health-related quality of life assessment and cognitive assessment. The primary efficacy endpoint is the change in obstructive AHI from baseline.

Study Overview

• Status: Active, not recruiting
• Conditions: Obstructive Sleep Apnea; Down Syndrome
• Intervention / Treatment: Drug: Atomoxetine and Oxybutynin (ato-oxy)

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 86721
      • University of Arizona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female participants between 6 to 17 years of age, inclusive, at the Screening Visit.
2. Known diagnosis of Down syndrome (trisomy 21, but not translocation or mosaicism)

Exclusion Criteria:

1. Presence of central sleep apnea on polysomnography (central AHI ≥ 5)
2. Currently using and adherent to positive airway pressure therapy (>4 hours per night for 70% of nights in the past 30 days based on device download or parent report)
3. Monoamine oxidase inhibitor use
4. Urinary retention
5. Prematurity < 32 weeks estimated gestational age
6. Seizure disorder
7. Untreated or inadequately treated hypothyroidism
8. Significant traumatic brain injury
9. Congenital heart disease and not cleared to participate by the patient's cardiologist
10. History of current, untreated depression
11. History of liver disease
12. 3+ or greater tonsillar hypertrophy
13. Positive urine pregnancy test
14. Hypoxemia independent of respiratory events on baseline polysomnography (≥5 minutes with oxygen saturation <90%)
15. Presence of central sleep apnea on baseline polysomnography (central AHI ≥ 5)

3. Absence of OSA defined as total AHI <5 on baseline polysomnography

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ato-oxy; 0.5 mg/kg (max 40 mg) atomoxetine and 5 mg oxybutynin	Drug: Atomoxetine and Oxybutynin (ato-oxy); 0.5 mg/kg atomoxetine (max 40 mg) and 5 mg oxybutynin by mouth nightly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
obstructive apnea-hypopnea index (oAHI)	change in number of obstructive apneas and hypopneas per hour on polysomnography from baseline (% change)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Obstructive Sleep Apnea-18 score (OSA-18)	Change in OSA-18 (a measure of health-related quality of life) from baseline. The OSA-18 score ranges from 18 to 136, with lower scores indicating better health-related quality of life.	6 months
Paired Associates Learning test	Change in Paired Associate Learning test total errors (a measure of memory) from baseline	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pediatric Quality of Life Inventory (PedsQL) total score	Change in PedsQL total score (a measure of health-related quality of life) from baseline. The PedsQL score ranges from 0-100, with higher scores indicating better health-related quality of life.	6 months
Processing speed	Change in processing speed as measured by A-MAP from baseline	6 months
Verbal IQ	Change in verbal IQ as measured by the Kaufman Brief IQ Test 2 from baseline	6 months
Verbal memory	Change in verbal memory as measured by A-MAP from baseline	6 months
Language	Change in child vocalizations/ hour as measured by LENA	6 months
Caregiver Global Impression of Change	Change in Caregiver Global Impression of Change from baseline. This will be assessed on a seven point scale answering the question: Since the start of this therapy, my child's overall status is: 1. Very much improved; 2. Much improved; 3. Minimally Improved; 4. No change; 5. Minimally worse; 6. Much worse or 7. Very much worse.	6 months
N1 sleep percentage	Change in N1 sleep percentage on polysomnography from baseline	6 months
REM sleep percentage	Change in REM sleep percentage on polysomnography from baseline	6 months
N3 sleep percentage	Change in N3 sleep percentage on polysomnography from baseline	6 months
Arousal Index	change in number of arousals per hour on polysomnography from baseline	6 months
Adaptive function	Change in Vineland 3 adaptive behavior composite scale from baseline	6 months
Executive Function	Change in Behavior Rating Inventory of Executive Function (BRIEF) Global Executive Composite from baseline	6 months
Attention Deficit Hyperactivity Disorder symptoms	Change in Conners-3 Attention Deficit Hyperactivity Disorder Index from baseline	6 months

Collaborators and Investigators

• Sponsor: University of Arizona
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH)

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: June 26, 2023
• First Submitted That Met QC Criteria: June 26, 2023
• First Posted (Actual): July 6, 2023

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, Inborn; Respiratory Tract Diseases; Neurobehavioral Manifestations; Respiration Disorders; Sleep Wake Disorders; Congenital Abnormalities; Abnormalities, Multiple; Apnea; Sleep Disorders, Intrinsic; Dyssomnias; Intellectual Disability; Sleep Apnea Syndromes; Chromosome Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Sleep Apnea, Obstructive; Down Syndrome; Organic Chemicals; Amines; Propylamines; Atomoxetine Hydrochloride; oxybutynin
• Other Study ID Numbers: 1908864846v2; R33HL151254 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified data will be made available via a database such as sleepdata.org.
• IPD Sharing Time Frame: Data will be made available following primary analysis and publication of primary study results.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No