Medications for Obstructive Sleep Apnea In Children With Down Syndrome

NCT ID: NCT04115878

Last Updated: 2025-08-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-21
• Study Completion Date: 2022-12-30

Brief Summary

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).

Conditions

Obstructive Sleep Apnea; Down Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

High dose ato-oxy

Group Type: ACTIVE_COMPARATOR

Atomoxetine and oxybutynin (ato-oxy)

Intervention Type: DRUG

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

Low dose ato-oxy

Group Type: ACTIVE_COMPARATOR

Atomoxetine and oxybutynin (ato-oxy)

Intervention Type: DRUG

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

Interventions

Atomoxetine and oxybutynin (ato-oxy)

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. 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.

2. Known diagnosis of Down syndrome (trisomy 21, but not translocation or mosaicism)

Exclusion Criteria

1. Hypoxemia independent of respiratory events on polysomnography (≥5 minutes with oxygen saturation <90%)

2. Presence of central sleep apnea on polysomnography (central AHI ≥ 5)

3. 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)

4. MAO inhibitor use

5. Urinary retention

6. Prematurity < 37 weeks estimated gestational age

7. Seizure disorder

8. Untreated or inadequately treated hypothyroidism

9. Significant traumatic brain injury

10. Congenital heart disease and not cleared to participate by the patient's cardiologist

11. History of current, untreated depression

12. History of liver disease

13. 3+ or greater tonsillar hypertrophy.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of Arizona

OTHER

Sponsor Role: lead

Responsible Party

Daniel A. Combs

Assistant Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Daniel Combs, MD

Role: PRINCIPAL_INVESTIGATOR

University of Arizona

Locations

University of Arizona

Tucson, Arizona, United States

Countries

United States

References

Combs D, Edgin J, Hsu CH, Bottrill K, Van Vorce H, Gerken B, Matloff D, La Rue S, Parthasarathy S. The combination of atomoxetine and oxybutynin for the treatment of obstructive sleep apnea in children with Down syndrome. J Clin Sleep Med. 2023 Dec 1;19(12):2065-2073. doi: 10.5664/jcsm.10764.

Reference Type: DERIVED

PMID: 37555595 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

R61HL151254

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1908864846

Identifier Type: -

Identifier Source: org_study_id