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

Primary Purpose

Obstructive Sleep Apnea, Down Syndrome

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Atomoxetine and Oxybutynin (ato-oxy)
Sponsored by
University of Arizona
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Obstructive Sleep Apnea

Eligibility Criteria

6 Years - 17 Years (Child)All SexesDoes not accept 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) 3. Absence of OSA defined as total AHI <5 on baseline polysomnography

Sites / Locations

  • University of ArizonaRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ato-oxy

Arm Description

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

Outcomes

Primary Outcome Measures

obstructive apnea-hypopnea index (oAHI)
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)
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
Change in Paired Associate Learning test total errors (a measure of memory) from baseline

Full Information

First Posted
June 26, 2023
Last Updated
August 18, 2023
Sponsor
University of Arizona
Collaborators
National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT05933603
Brief Title
Medications for Obstructive Sleep Apnea to Improve Cognition in Children With Down Syndrome
Acronym
MOSAIC
Official Title
Medications for Obstructive Sleep Apnea to Improve Cognition in Children With Down Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 1, 2023 (Actual)
Primary Completion Date
August 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Arizona
Collaborators
National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

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
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obstructive Sleep Apnea, Down Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
36 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ato-oxy
Arm Type
Experimental
Arm Description
0.5 mg/kg (max 40 mg) atomoxetine and 5 mg oxybutynin
Intervention Type
Drug
Intervention Name(s)
Atomoxetine and Oxybutynin (ato-oxy)
Intervention Description
0.5 mg/kg atomoxetine (max 40 mg) and 5 mg oxybutynin by mouth nightly
Primary Outcome Measure Information:
Title
obstructive apnea-hypopnea index (oAHI)
Description
change in number of obstructive apneas and hypopneas per hour on polysomnography from baseline (% change)
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Obstructive Sleep Apnea-18 score (OSA-18)
Description
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.
Time Frame
6 months
Title
Paired Associates Learning test
Description
Change in Paired Associate Learning test total errors (a measure of memory) from baseline
Time Frame
6 months
Other Pre-specified Outcome Measures:
Title
Pediatric Quality of Life Inventory (PedsQL) total score
Description
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.
Time Frame
6 months
Title
Processing speed
Description
Change in processing speed as measured by A-MAP from baseline
Time Frame
6 months
Title
Verbal IQ
Description
Change in verbal IQ as measured by the Kaufman Brief IQ Test 2 from baseline
Time Frame
6 months
Title
Verbal memory
Description
Change in verbal memory as measured by A-MAP from baseline
Time Frame
6 months
Title
Language
Description
Change in child vocalizations/ hour as measured by LENA
Time Frame
6 months
Title
Caregiver Global Impression of Change
Description
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.
Time Frame
6 months
Title
N1 sleep percentage
Description
Change in N1 sleep percentage on polysomnography from baseline
Time Frame
6 months
Title
REM sleep percentage
Description
Change in REM sleep percentage on polysomnography from baseline
Time Frame
6 months
Title
N3 sleep percentage
Description
Change in N3 sleep percentage on polysomnography from baseline
Time Frame
6 months
Title
Arousal Index
Description
change in number of arousals per hour on polysomnography from baseline
Time Frame
6 months
Title
Executive Function
Description
Change in Behavior Rating Inventory of Executive Function (BRIEF) Global Executive Composite from baseline
Time Frame
6 months
Title
Adaptive function
Description
Change in Vineland 3 adaptive behavior composite scale from baseline
Time Frame
6 months
Title
Attention Deficit Hyperactivity Disorder symptoms
Description
Change in Conners-3 Attention Deficit Hyperactivity Disorder Index from baseline
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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) 3. Absence of OSA defined as total AHI <5 on baseline polysomnography
Facility Information:
Facility Name
University of Arizona
City
Tucson
State/Province
Arizona
ZIP/Postal Code
86721
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lauren Melcher
Phone
520-403-0383
Email
lmelcher@arizona.edu
First Name & Middle Initial & Last Name & Degree
Daniel Combs, MD

12. IPD Sharing Statement

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

Learn more about this trial

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

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