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

NCT05933603 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 1908864846v2R33HL151254
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Obstructive Sleep Apnea; Down Syndrome

Outcome Measures

Primary Outcomes (1)

• obstructive apnea-hypopnea index (oAHI)

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

  6 months

Secondary Outcomes (2)

• Obstructive Sleep Apnea-18 score (OSA-18)

  6 months

• Paired Associates Learning test

  6 months

Other Outcomes (13)

• Pediatric Quality of Life Inventory (PedsQL) total score

  6 months

• Processing speed

  6 months

• Verbal IQ

  6 months

Study Arms (1)

Ato-oxy

EXPERIMENTAL

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

Drug: Atomoxetine and Oxybutynin (ato-oxy)

Interventions

Atomoxetine and Oxybutynin (ato-oxy) DRUG

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

Ato-oxy

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• 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
• + 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)

Sponsors & Collaborators

• University of Arizona: lead
• National Institutes of Health (NIH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Arizona

Tucson, Arizona, 86721, United States

RECRUITING

MeSH Terms

Conditions

Sleep Apnea, Obstructive; Down Syndrome

Interventions

Atomoxetine Hydrochloride; oxybutynin

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2023
• First Posted: July 6, 2023
• Study Start: September 29, 2023
• Primary Completion: September 1, 2025
• Study Completion: December 1, 2025
• Last Updated: August 26, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will be made available following primary analysis and publication of primary study results.

Locations

US (1)