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Medications for Obstructive Sleep Apnea In Children With Down Syndrome (MOSAIC)

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ClinicalTrials.gov Identifier: NCT04115878
Recruitment Status : Not yet recruiting
First Posted : October 4, 2019
Last Update Posted : October 8, 2019
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Daniel A. Combs, University of Arizona

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).


Condition or disease Intervention/treatment Phase
Obstructive Sleep Apnea Down Syndrome Drug: Atomoxetine and oxybutynin (ato-oxy) Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 27 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Evaluation of Atomoxetine and Oxybutynin for Obstructive Sleep Apnea in Children With Down Syndrome
Estimated Study Start Date : November 2019
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : September 2021


Arm Intervention/treatment
Active Comparator: High dose ato-oxy Drug: Atomoxetine and oxybutynin (ato-oxy)
Low dose ato-oxy will include 0.5 mg/kg/day of atomoxetine (max 40 mg) in combination with 5 mg oxybutynin High dose ato-oxy will include 1.2 mg/kg/day atomoxetine (max 80 mg) and 5 mg oxybutynin

Active Comparator: Low dose ato-oxy Drug: Atomoxetine and oxybutynin (ato-oxy)
Low dose ato-oxy will include 0.5 mg/kg/day of atomoxetine (max 40 mg) in combination with 5 mg oxybutynin High dose ato-oxy will include 1.2 mg/kg/day atomoxetine (max 80 mg) and 5 mg oxybutynin




Primary Outcome Measures :
  1. obstructive apnea-hypopnea index (oAHI) [ Time Frame: four weeks ]
    change in number of obstructive apneas and hypopneas per hour on polysomnography from baseline (% change)


Secondary Outcome Measures :
  1. Obstructive Sleep Apnea-18 score (OSA-18) [ Time Frame: four weeks ]
    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.

  2. Arousal Index [ Time Frame: four weeks ]
    change in number of arousals per hour on polysomnography from baseline


Other Outcome Measures:
  1. Pediatric Quality of Life Inventory (PedsQL) total score [ Time Frame: four weeks ]
    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.

  2. Caregiver Global Impression of Change [ Time Frame: four weeks ]
    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.

  3. N1 sleep percentage [ Time Frame: four weeks ]
    Change in N1 sleep percentage on polysomnography from baseline

  4. REM sleep percentage [ Time Frame: four weeks ]
    Change in REM sleep percentage on polysomnography from baseline

  5. N3 sleep percentage [ Time Frame: four weeks ]
    Change in N3 sleep percentage on polysomnography from baseline



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04115878


Contacts
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Contact: Christopher Morton (520) 626-4857 cjmorton@email.arizona.edu

Locations
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United States, Arizona
University of Arizona Not yet recruiting
Tucson, Arizona, United States, 85721
Contact: Christopher Morton    520-626-4857    cjmorton@email.arizona.edu   
Principal Investigator: Daniel Combs, MD         
Sponsors and Collaborators
University of Arizona
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Daniel Combs, MD University of Arizona

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Responsible Party: Daniel A. Combs, Assistant Professor of Pediatrics, University of Arizona
ClinicalTrials.gov Identifier: NCT04115878     History of Changes
Other Study ID Numbers: 1908864846
R61HL151254 ( U.S. NIH Grant/Contract )
First Posted: October 4, 2019    Key Record Dates
Last Update Posted: October 8, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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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
Keywords provided by Daniel A. Combs, University of Arizona:
atomoxetine
oxybutynin
Additional relevant MeSH terms:
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Apnea
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Down Syndrome
Syndrome
Disease
Pathologic Processes
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn
Mandelic Acids
Oxybutynin
Atomoxetine Hydrochloride
Adrenergic Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Adrenergic Agents