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

Obstructive Sleep Apnea Clinical Trial

— MOSAIC  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05933603
• Other study ID #: 1908864846v2
• Secondary ID: R33HL151254
• Status: Recruiting
• Phase: Phase 2
• Start date: August 1, 2023
• Est. completion date: December 2025

Study information

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

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: December 2025
• Est. primary completion date: August 2025
• 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.

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)

3. Absence of OSA defined as total AHI <5 on baseline polysomnography

Related Conditions & MeSH terms

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

Intervention

Drug:
• Atomoxetine and Oxybutynin (ato-oxy)
0.5 mg/kg atomoxetine (max 40 mg) and 5 mg oxybutynin by mouth nightly

Locations

Country	Name	City	State
United States	University of Arizona	Tucson	Arizona

Sponsors (3)

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

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.	6 months
Other	Processing speed	Change in processing speed as measured by A-MAP from baseline	6 months
Other	Verbal IQ	Change in verbal IQ as measured by the Kaufman Brief IQ Test 2 from baseline	6 months
Other	Verbal memory	Change in verbal memory as measured by A-MAP from baseline	6 months
Other	Language	Change in child vocalizations/ hour as measured by LENA	6 months
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.	6 months
Other	N1 sleep percentage	Change in N1 sleep percentage on polysomnography from baseline	6 months
Other	REM sleep percentage	Change in REM sleep percentage on polysomnography from baseline	6 months
Other	N3 sleep percentage	Change in N3 sleep percentage on polysomnography from baseline	6 months
Other	Arousal Index	change in number of arousals per hour on polysomnography from baseline	6 months
Other	Executive Function	Change in Behavior Rating Inventory of Executive Function (BRIEF) Global Executive Composite from baseline	6 months
Other	Adaptive function	Change in Vineland 3 adaptive behavior composite scale from baseline	6 months
Other	Attention Deficit Hyperactivity Disorder symptoms	Change in Conners-3 Attention Deficit Hyperactivity Disorder Index from baseline	6 months
Primary	obstructive apnea-hypopnea index (oAHI)	change in number of obstructive apneas and hypopneas per hour on polysomnography from baseline (% change)	6 months
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.	6 months
Secondary	Paired Associates Learning test	Change in Paired Associate Learning test total errors (a measure of memory) from baseline	6 months