Medications for Obstructive Sleep Apnea In Children With Down Syndrome

Obstructive Sleep Apnea Clinical Trial

— MOSAIC  

Official title:

Evaluation of Atomoxetine and Oxybutynin for Obstructive Sleep Apnea in Children With Down Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04115878
• Other study ID #: 1908864846
• Secondary ID: R61HL151254
• Status: Completed
• Phase: Phase 2
• Start date: October 21, 2020
• Est. completion date: December 30, 2022

Study information

• Verified date: May 2023
• Source: University of Arizona
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: December 30, 2022
• Est. primary completion date: December 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Apnea
• Down Syndrome
• Obstructive Sleep Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive
• Syndrome

Intervention

Drug:
• 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

Locations

Country	Name	City	State
United States	University of Arizona	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
University of Arizona	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pediatric Quality of Life Inventory (PedsQL) total score	Change in PedsQL total score (a measure of health-related quality of life) from baseline. The PedsQL score ranges from 0-100, with higher scores indicating better health-related quality of life.	four weeks
Other	Caregiver Global Impression of Change	Change in Caregiver Global Impression of Change from baseline. This will be assessed on a seven point scale answering the question: Since the start of this therapy, my child's overall status is: 1. Very much improved; 2. Much improved; 3. Minimally Improved; 4. No change; 5. Minimally worse; 6. Much worse or 7. Very much worse.	four weeks
Other	N1 sleep percentage	Change in N1 sleep percentage on polysomnography from baseline	four weeks
Other	REM sleep percentage	Change in REM sleep percentage on polysomnography from baseline	four weeks
Other	N3 sleep percentage	Change in N3 sleep percentage on polysomnography from baseline	four weeks
Primary	obstructive apnea-hypopnea index (oAHI)	change in number of obstructive apneas and hypopneas per hour on polysomnography from baseline (% change)	four weeks
Secondary	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
Secondary	Arousal Index	change in number of arousals per hour on polysomnography from baseline	four weeks