Clinical trial NCT04115878: Medications for Obstructive Sleep Apnea In Children With Down Syndrome
Official title: Evaluation of Atomoxetine and Oxybutynin for Obstructive Sleep Apnea in Children With Down Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Obstructive Sleep Apnea
Down Syndrome
Keywords: atomoxetine
oxybutynin
Lead sponsor: University of Arizona
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2019-10-04
Enrollment: 22
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: obstructive apnea-hypopnea index (oAHI)
timeFrame: four weeks
Secondary outcomes:
measure: Obstructive Sleep Apnea-18 score (OSA-18)
timeFrame: four weeks
measure: Arousal Index
timeFrame: four weeks
Other outcomes:
measure: Pediatric Quality of Life Inventory (PedsQL) total score
timeFrame: four weeks
measure: Caregiver Global Impression of Change
timeFrame: four weeks
measure: N1 sleep percentage
timeFrame: four weeks
measure: REM sleep percentage
timeFrame: four weeks
measure: N3 sleep percentage
timeFrame: four weeks
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
Study officials:
affiliation: University of Arizona
name: Daniel Combs, MD
role: PRINCIPAL_INVESTIGATOR
References: