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

Study Overview
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Brief Summary
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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.

Official Title
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Medications for Obstructive Sleep Apnea to Improve Cognition in Children With Down Syndrome

Conditions
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Obstructive Sleep Apnea, Down Syndrome

Intervention / Treatment
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* Drug: Atomoxetine and Oxybutynin (ato-oxy)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participants between 6 to 17 years of age, inclusive, at the Screening Visit. Known diagnosis of Down syndrome (trisomy 21, but not translocation or mosaicism) Exclusion Criteria: Presence of central sleep apnea on polysomnography (central AHI ≥ 5) 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) Monoamine oxidase inhibitor use Urinary retention Prematurity < 32 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 3+ or greater tonsillar hypertrophy Positive urine pregnancy test Hypoxemia independent of respiratory events on baseline polysomnography (≥5 minutes with oxygen saturation <90%) Presence of central sleep apnea on baseline polysomnography (central AHI ≥ 5) 3. Absence of OSA defined as total AHI <5 on baseline polysomnography

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 |