Medications for Obstructive Sleep Apnea In Children With Down Syndrome

Study Overview
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Brief Summary
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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).

Official Title
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Evaluation of Atomoxetine and Oxybutynin for Obstructive Sleep Apnea 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. 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) Exclusion Criteria: 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 3+ or greater tonsillar hypertrophy.

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
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: High dose ato-oxy<br> | Drug: Atomoxetine and oxybutynin (ato-oxy)<br>* 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<br>|
| Active Comparator: Low dose ato-oxy<br> | Drug: Atomoxetine and oxybutynin (ato-oxy)<br>* 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<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) | four weeks | 

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. | four weeks | 
| Arousal Index | change in number of arousals per hour on polysomnography from baseline | four weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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atomoxetine, oxybutynin