Endotype DIrected Treatment for OSA in Down Syndrome

NCT07280468 | Not Yet Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: STUDY00007297IDD-2024C1-37111
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 4

Brief Summary

Down syndrome is the most common genetic cause of intellectual disability. People with Down syndrome often have obstructive sleep apnea (OSA), a condition where people have difficulties with breathing while asleep. OSA can lead to poor sleep, worse quality of life, behavior problems and more difficulties with thinking ("cognitive impairment"). Current treatments for OSA in people with Down syndrome are not very effective or require surgery. The combination of 2 medications, atomoxetine and oxybutynin ("ato-oxy") is a promising treatment for OSA in people with Down syndrome, but ato-oxy does not work for everyone with Down syndrome. Similarly, oxygen is effective for OSA in some people, but does not work for everyone. This study will evaluate the use a precision medicine approach to increase the effectiveness of OSA treatment in people with Down syndrome. The study will compare two groups. In the first group, everyone will be treated with ato-oxy. In the second group, a precision medicine approach will be used to assign participants to either ato-oxy or oxygen therapy, based on the specific reasons they have OSA. The research team will enroll 200 children (age 6-17 years old) and adults with Down syndrome and OSA from five sites across the country. Half of participants will randomly receive ato-oxy while the other will receive either oxygen or ato-oxy dependent upon which treatment would be expected to work better for them. The research team will measure OSA severity, quality of life, behavior and cognition at the start of the study and after 12 months of treatment for every participant. The study will also track any treatment side effects for each treatment group.

Conditions

Obstructive Sleep Apnea (OSA); Down Syndrome

Keywords

Down syndrome; obstructive sleep apnea; ato-oxy; precision medicine; oxygen; atomoxetine; oxybutynin

Outcome Measures

Primary Outcomes (1)

• obstructive apnea-hypopnea index (oAHI)

  change in number of obstructive apneas and hypopneas per hour on polysomnography from baseline. Decreased oAHI indicates better outcome.

  12 months

Secondary Outcomes (2)

• Change in caregiver Pediatric Quality of Life (PedsQL) score from baseline

  12 months

• Change in Paired Associate Learning test total adjusted errors from baseline

  12 months

Other Outcomes (20)

• Change in processing speed (Arizona Memory Assessment for Preschoolers and Special Populations [A-MAP] task) from baseline.

  12 months

• Change in total IQ (Kaufman Brief Intelligence Test 2) from baseline

  12 months

• Change in non-verbal IQ (Kaufman Brief Intelligence Test 2) from baseline

  12 months

Study Arms (2)

Uniform therapy (ato-oxy)

ACTIVE COMPARATOR

All participants receive the combination of atomoxetine and oxybutynin (ato-oxy) once nightly

Drug: ato-oxy

Endotype Directed Treatment

EXPERIMENTAL

Participants receive either atomoxetine and oxybutynin (ato-oxy) or oxygen nightly. Participants receive the treatment expected to be most beneficial to them based on their baseline sleep study and OSA characteristics (OSA endotype).

Drug: ato-oxy; Drug: Oxygen

Interventions

ato-oxy DRUG

0.5 mg/kg (max 40 mg) of atomoxetine and 5mg oxybutynin taken nightly.

Also known as: atomoxetine and oxybutynin

Endotype Directed Treatment; Uniform therapy (ato-oxy)

Oxygen DRUG

Oxygen via nasal cannula used nightly

Endotype Directed Treatment

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 6 years or older
• Down syndrome diagnosis
• Any gender or ethnicity
• Adults without a legally authorized representative must have a caregiver/support person that can co-sign consent and complete study questionnaires.

You may not qualify if:

• 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/caregiver report)
• MAO inhibitor use
• Urinary retention
• Seizure disorder
• Untreated or inadequately treated hypothyroidism
• Significant traumatic brain injury
• Not cleared to participate in the study by their cardiologist for individuals with congenital heart disease requiring follow up with cardiology at least once in the past year
• History of current, untreated depression
• History of liver disease (not including metabolic dysfunction-associated steatotic liver disease)
• + or greater tonsillar hypertrophy (for children only, no restriction for adults)

Sponsors & Collaborators

• University of Arizona: lead
• Patient-Centered Outcomes Research Institute: collaborator

Study Sites (4)

University of Arizona

Tucson, Arizona, 85724, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Advocate Medical Group Adult Down Syndrome Center

Park Ridge, Illinois, 60068, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Combs D, Edgin J, Hsu CH, Bottrill K, Van Vorce H, Gerken B, Matloff D, La Rue S, Parthasarathy S. The combination of atomoxetine and oxybutynin for the treatment of obstructive sleep apnea in children with Down syndrome. J Clin Sleep Med. 2023 Dec 1;19(12):2065-2073. doi: 10.5664/jcsm.10764.

  PMID: 37555595 BACKGROUND

MeSH Terms

Conditions

Sleep Apnea, Obstructive; Down Syndrome

Interventions

Atomoxetine Hydrochloride; oxybutynin; Oxygen

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; Chalcogens; Elements; Inorganic Chemicals; Gases

Study Officials

• Daniel Combs, MD

  University of Arizona

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Natalie Provencio-Dean

CONTACT

520-403-6165; nataliep@arizona.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Pediatrics and Medicine

Study Record Dates

• First Submitted: November 23, 2025
• First Posted: December 12, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2030
• Last Updated: December 12, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

US (4)