Clinical trial NCT05933603: Medications for Obstructive Sleep Apnea to Improve Cognition in Children With Down Syndrome
Official title: Medications for Obstructive Sleep Apnea to Improve Cognition in Children With Down Syndrome
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Obstructive Sleep Apnea
Down Syndrome
Lead sponsor: University of Arizona
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2023-07-06
Enrollment: 36
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: obstructive apnea-hypopnea index (oAHI)
timeFrame: 6 months
Secondary outcomes:
measure: Obstructive Sleep Apnea-18 score (OSA-18)
timeFrame: 6 months
measure: Paired Associates Learning test
timeFrame: 6 months
Other outcomes:
measure: Pediatric Quality of Life Inventory (PedsQL) total score
timeFrame: 6 months
measure: Processing speed
timeFrame: 6 months
measure: Verbal IQ
timeFrame: 6 months
measure: Verbal memory
timeFrame: 6 months
measure: Language
timeFrame: 6 months
measure: Caregiver Global Impression of Change
timeFrame: 6 months
measure: N1 sleep percentage
timeFrame: 6 months
measure: REM sleep percentage
timeFrame: 6 months
measure: N3 sleep percentage
timeFrame: 6 months
measure: Arousal Index
timeFrame: 6 months
measure: Executive Function
timeFrame: 6 months
measure: Adaptive function
timeFrame: 6 months
measure: Attention Deficit Hyperactivity Disorder symptoms
timeFrame: 6 months
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
Study officials:
References: