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

• ClinicalTrials.gov Identifier: NCT05933603
• Recruitment Status: Recruiting
• First Posted: July 6, 2023
• Last Update Posted: August 22, 2023
• Sponsor: University of Arizona
• Collaborators: National Institutes of Health (NIH); National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): University of Arizona

Tracking Information

• First Submitted Date: June 26, 2023
• First Posted Date: July 6, 2023
• Last Update Posted Date: August 22, 2023
• Actual Study Start Date: August 1, 2023
• Estimated Primary Completion Date: August 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 26, 2023)

obstructive apnea-hypopnea index (oAHI) [ Time Frame: 6 months ]

change in number of obstructive apneas and hypopneas per hour on polysomnography from baseline (% change)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 26, 2023)

• Obstructive Sleep Apnea-18 score (OSA-18) [ Time Frame: 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 [ Time Frame: 6 months ]
  Change in Paired Associate Learning test total errors (a measure of memory) from baseline

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: August 18, 2023)

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

Original Other Pre-specified Outcome Measures (submitted: June 26, 2023)

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

Descriptive Information

• Brief Title: 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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Obstructive Sleep Apnea
• Down Syndrome

Intervention

Drug: Atomoxetine and Oxybutynin (ato-oxy)

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

Study Arms

Experimental: Ato-oxy

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

Intervention: Drug: Atomoxetine and Oxybutynin (ato-oxy)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 26, 2023): 36
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2025
• Estimated Primary Completion Date: August 2025 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Years to 17 Years (Child)
• Accepts Healthy Volunteers: No
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05933603
• Other Study ID Numbers: 1908864846v2; R33HL151254 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: De-identified data will be made available via a database such as sleepdata.org.
• Time Frame: Data will be made available following primary analysis and publication of primary study results.

• Current Responsible Party: University of Arizona
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Arizona
• Original Study Sponsor: Same as current

Collaborators

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

• Investigators: Not Provided
• PRS Account: University of Arizona
• Verification Date: June 2023