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

Phase 2

Recruiting

• Conditions: Obstructive Sleep Apnea; Down Syndrome
• Interventions: Drug: Atomoxetine and Oxybutynin (ato-oxy)

• Registration Number: NCT05933603
• Lead Sponsor: University of Arizona

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-06-26
• Study First Submitted QC: 2023-06-26
• Study First Posted: 2023-07-06
• Study Start: 2023-09-29
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-22
• Last Update Posted: 2024-08-26
• Primary Completion: 2025-09
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 36

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ato-oxy	Atomoxetine and Oxybutynin (ato-oxy)	0.5 mg/kg (max 40 mg) atomoxetine and 5 mg oxybutynin

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Obstructive Sleep Apnea-18 score (OSA-18)	6 months	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.
Paired Associates Learning test	6 months	Change in Paired Associate Learning test total errors (a measure of memory) from baseline

Trial Locations

Locations (1)

University of Arizona; 🇺🇸 Tucson, Arizona, United States