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

University of Arizona

Status and phase: Enrolling; Phase 2

Conditions: Down Syndrome; Obstructive Sleep Apnea

Treatments: Drug: Atomoxetine and Oxybutynin (ato-oxy)

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05933603

1908864846v2

R33HL151254 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Enrollment: 36 estimated patients

Sex: All

Ages: 6 to 17 years old

Volunteers: No Healthy Volunteers

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)

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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36 participants in 1 patient group

Ato-oxy

Experimental group

Description:

0.5 mg/kg (max 40 mg) atomoxetine and 5 mg oxybutynin

Treatment:

Drug: Atomoxetine and Oxybutynin (ato-oxy)