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

Sponsor

University of Arizona (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05933603

Collaborator

National Institutes of Health (NIH) (NIH), National Heart, Lung, and Blood Institute (NHLBI) (NIH)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Obstructive Sleep Apnea Down Syndrome	Drug: Atomoxetine and Oxybutynin (ato-oxy)	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

36 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jul 1, 2023

Anticipated Primary Completion Date :

Aug 1, 2025

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ato-oxy 0.5 mg/kg (max 40 mg) atomoxetine and 5 mg oxybutynin	Drug: Atomoxetine and Oxybutynin (ato-oxy) 0.5 mg/kg atomoxetine (max 40 mg) and 5 mg oxybutynin by mouth nightly

Arm

Intervention/Treatment

Experimental: Ato-oxy

0.5 mg/kg (max 40 mg) atomoxetine and 5 mg oxybutynin

Drug: Atomoxetine and Oxybutynin (ato-oxy)

0.5 mg/kg atomoxetine (max 40 mg) and 5 mg oxybutynin by mouth nightly

Outcome Measures

Primary Outcome Measures

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

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

Other Outcome Measures

Pediatric Quality of Life Inventory (PedsQL) total score [6 months]
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.
Processing speed [6 months]
Change in processing speed as measured by A-MAP from baseline
Verbal IQ [6 months]
Change in verbal IQ as measured by the Kaufman Brief IQ Test 2 from baseline
Verbal memory [6 months]
Change in verbal memory as measured by A-MAP from baseline
Language [6 months]
Change in child vocalizations/ hour as measured by LENA
Caregiver Global Impression of Change [6 months]
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.
N1 sleep percentage [6 months]
Change in N1 sleep percentage on polysomnography from baseline
REM sleep percentage [6 months]
Change in REM sleep percentage on polysomnography from baseline
N3 sleep percentage [6 months]
Change in N3 sleep percentage on polysomnography from baseline
Arousal Index [6 months]
change in number of arousals per hour on polysomnography from baseline
Executive Function [6 months]
Change in BRIEF Global Executive Composite from baseline
Adaptive function [6 months]
Change in Vineland 3 adaptive behavior composite scale from baseline
Attention Deficit Hyperactivity Disorder symptoms [6 months]
Change in Conners-3 ADHD Index from baseline

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female participants between 6 to 17 years of age, inclusive, at the Screening Visit.
Known diagnosis of Down syndrome (trisomy 21, but not translocation or mosaicism)

Exclusion Criteria:

Presence of central sleep apnea on polysomnography (central AHI ≥ 5)
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)
Monoamine oxidase inhibitor use
Urinary retention
Prematurity < 32 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
Positive urine pregnancy test
Hypoxemia independent of respiratory events on baseline polysomnography (≥5 minutes with oxygen saturation <90%)
Presence of central sleep apnea on baseline polysomnography (central AHI ≥ 5)
Absence of OSA defined as total AHI <5 on baseline polysomnography