Obstructive Sleep Apnea (OSA)Phase 4EDIT OSANCT07280468
Endotype DIrected Treatment for OSA in Down Syndrome
A Phase 4 study testing ato-oxy and Oxygen in people with Obstructive Sleep Apnea (OSA) and Down Syndrome, run by University of Arizona at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Obstructive Sleep Apnea (OSA), Down Syndrome
- What is being tested?
- ato-oxy and Oxygen
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 5 sitesUnited States
- Study dates
- 14 Mar 2026to Jan 2030
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 10Show fewer
- 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)
- 3+ or greater tonsillar hypertrophy (for children only, no restriction for adults)
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
United States5 sites, 5 recruiting
- Recruiting
University of Miami
Miami, Florida, 33136
Ignacio Tapia, 305-243-6162, itapia@miami.edu
Ignacio Tapia
- Recruiting
Advocate Medical Group Adult Down Syndrome Center
Park Ridge, Illinois, 60068
Alex Albers, 920-288-3129, alexander.albers@aah.org
Brian Chicoine
- Recruiting
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Ruth Bradford, 267-426-5747, BRADFORD@chop.edu
Chris Cielo
- Recruiting
University of California San Diego
San Diego, California, 92123
Jasmine Tinoco, 858-576-1700 ext. 224604, j1tinoco@health.ucsd.edu
Rakesh Bhattacharjee
- Recruiting
University of Arizona
Tucson, Arizona, 85724
Natalie Provencio-Dean, 520-403-6165, nataliep@arizona.edu
About this study
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.
Read the detailed description
Background and Significance: Obstructive sleep apnea (OSA) is one of the most common comorbidities present in individuals with Down syndrome. In children without Down syndrome, OSA has a prevalence of 2-5%2 whereas the prevalence of OSA in children with Down syndrome has been estimated at 50-79%. Similarly, OSA occurs in 12% of adults without Down syndrome, but occurs in 80-100% of adults with Down syndrome. In studies by our group and others, OSA has been associated with neurocognitive impairment and impaired health-related quality of life (HRQOL) in children and adults with Down syndrome. Cognition and HRQOL have been shown to improve with effective treatment of OSA in people with Down syndrome. However, current treatments for OSA have limited effectiveness in people with Down syndrome. Adenotonsillectomy has been shown to have limited efficacy, as 65-73% of children with Down syndrome have residual OSA after adenotonsillectomy. Similarly, positive airway pressure (PAP) effectiveness is limited by poor adherence. Hypoglossal nerve stimulation has emerged as a new treatment but is an invasive procedure that involves a surgically placed implant that many individuals may prefer to avoid. Additionally, surgical complications are more common in people with DS compared to people without Down syndrome. Use is also limited in younger children with significant growth remaining. Given this, there is a great need for effective alternative therapies. The combination of atomoxetine and oxybutynin (ato-oxy) is a promising alternative therapy but is not effective in all individuals with Down syndrome. Similarly, oxygen therapy is often considered as an alternative treatment for OSA but is not effective in all patients. Underlying physiologic patient characteristics (OSA endotype) have predicted treatment response for OSA with both ato-oxy and oxygen. OSA endotype-directed treatment appears to be a means to identify the right treatment for the right patient, which may have greater effectiveness compared to the same treatment for all individuals.
Study Aims: The goal of this study is to determine if a precision medicine approach, endotype-directed treatment, is more effective than a one-size fits all treatment approach (ato-oxy) for OSA in people with Down syndrome. Specific aims of the study include: Aim 1: To compare the effectiveness of ato-oxy therapy versus precision medicine (endotype-directed) treatment for OSA in people with Down syndrome over 12 months; Aim 2: To compare the effectiveness of ato-oxy versus precision medicine (endotype-directed) treatment approach for key patient-centered outcomes (PCOs), including health-related quality of life, behavior and cognition over 12 months; Aim #3: To compare the adverse effects of ato-oxy versus precision medicine (endotype-directed) treatment.
Study Description: This is a randomized clinical trial comparing ato-oxy versus endotype-directed treatment for OSA in children and adults with DS. We will enroll 200 participants with Down syndrome and OSA (100 children age 6-17 years, 100 adults age 18+ years). Participants will be recruited from five clinical sites from across the country as well as via outreach. Participants will be randomized 1:1 at an individual level to either ato-oxy or endotype-directed treatment, which would be either oxygen or ato-oxy dependent upon the individual's OSA endotype. The study primary outcome is obstructive apnea-hypopnea index, the primary measure of OSA severity. Secondary study outcomes include measures of HRQOL, behavior, cognition and adverse effects. Participants will receive treatment and be followed for a total of 12 months during the study.
- Conditions
- Obstructive Sleep Apnea (OSA), Down Syndrome
- Being tested
- ato-oxy, Oxygen
- Keywords
- Down syndrome, obstructive sleep apnea, ato-oxy, precision medicine, oxygen, atomoxetine, oxybutynin
- Medical subject headings
- Sleep Apnea, Obstructive, Down Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ato-oxyDrug
Also called atomoxetine and oxybutynin
0.5 mg/kg (max 40 mg) of atomoxetine and 5mg oxybutynin taken nightly.
OxygenDrug
Oxygen via nasal cannula used nightly
| Study group | Role | What they receive |
|---|---|---|
| Uniform therapy (ato-oxy) | Active comparator | All participants receive the combination of atomoxetine and oxybutynin (ato-oxy) once nightly Receives: 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). Receives: Drug: ato-oxy; Drug: Oxygen |
What is being measured
The primary outcome is the main question the study is designed to answer.
obstructive apnea-hypopnea index (oAHI)
change in number of obstructive apneas and hypopneas per hour on polysomnography from baseline. Decreased oAHI indicates better outcome.
Measured: 12 months
Secondary outcomes (2)
Change in caregiver Pediatric Quality of Life (PedsQL) score from baseline
Change in caregiver reported quality of life as measured by PedsQL, higher scores indicate better outcome.
Measured: 12 months
Change in Paired Associate Learning test total adjusted errors from baseline
Change in Paired Associate Learning test total errors (a measure of memory) from baseline. Fewer errors indicate better outcome
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2025
- Study start14 Mar 2026
- Primary completionJan 2030 (estimated)
- Study completionJan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Obstructive Sleep Apnea (OSA)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Arizona
- Sponsor type
- University, hospital or other
- Collaborators
- Patient-Centered Outcomes Research Institute
- Responsible party
- Principal investigator, Daniel A. Combs, University of Arizona
- Investigators
- Daniel Combs, MD, Principal investigator, University of Arizona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07280468
- Sponsor's protocol ID
- STUDY00007297
- Other IDs
- IDD-2024C1-37111
- Acronym
- EDIT OSA
- Status last verified
- Sep 2026
- First submitted
- 23 Nov 2025
- Last updated
- 3 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified data will be made available.
Publications
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.
PubMed 37555595
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Endotype DIrected Treatment for OSA in Down Syndrome
- ClinicalTrials.gov ID
- NCT07280468
- Acronym / sponsor ID
- EDIT OSA / STUDY00007297
- Conditions
- Obstructive Sleep Apnea (OSA), Down Syndrome
- Keywords
- Down syndrome, obstructive sleep apnea, ato-oxy, precision medicine, oxygen, atomoxetine, oxybutynin
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- University of ArizonaUniversity, hospital or other
- Collaborators
- Patient-Centered Outcomes Research Institute
- Study start
- 14 Mar 2026 (actual)
- Primary completion
- Jan 2030 (estimated)
- Study completion
- Jan 2030 (estimated)
- First posted
- 12 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Background and Significance: Obstructive sleep apnea (OSA) is one of the most common comorbidities present in individuals with Down syndrome. In children without Down syndrome, OSA has a prevalence of 2-5%2 whereas the prevalence of OSA in children with Down syndrome has been estimated at 50-79%. Similarly, OSA occurs in 12% of adults without Down syndrome, but occurs in 80-100% of adults with Down syndrome. In studies by our group and others, OSA has been associated with neurocognitive impairment and impaired health-related quality of life (HRQOL) in children and adults with Down syndrome. Cognition and HRQOL have been shown to improve with effective treatment of OSA in people with Down syndrome. However, current treatments for OSA have limited effectiveness in people with Down syndrome. Adenotonsillectomy has been shown to have limited efficacy, as 65-73% of children with Down syndrome have residual OSA after adenotonsillectomy. Similarly, positive airway pressure (PAP) effectiveness is limited by poor adherence. Hypoglossal nerve stimulation has emerged as a new treatment but is an invasive procedure that involves a surgically placed implant that many individuals may prefer to avoid. Additionally, surgical complications are more common in people with DS compared to people without Down syndrome. Use is also limited in younger children with significant growth remaining. Given this, there is a great need for effective alternative therapies. The combination of atomoxetine and oxybutynin (ato-oxy) is a promising alternative therapy but is not effective in all individuals with Down syndrome. Similarly, oxygen therapy is often considered as an alternative treatment for OSA but is not effective in all patients. Underlying physiologic patient characteristics (OSA endotype) have predicted treatment response for OSA with both ato-oxy and oxygen. OSA endotype-directed treatment appears to be a means to identify the right treatment for the right patient, which may have greater effectiveness compared to the same treatment for all individuals.
Study Aims: The goal of this study is to determine if a precision medicine approach, endotype-directed treatment, is more effective than a one-size fits all treatment approach (ato-oxy) for OSA in people with Down syndrome. Specific aims of the study include: Aim 1: To compare the effectiveness of ato-oxy therapy versus precision medicine (endotype-directed) treatment for OSA in people with Down syndrome over 12 months; Aim 2: To compare the effectiveness of ato-oxy versus precision medicine (endotype-directed) treatment approach for key patient-centered outcomes (PCOs), including health-related quality of life, behavior and cognition over 12 months; Aim #3: To compare the adverse effects of ato-oxy versus precision medicine (endotype-directed) treatment.
Study Description: This is a randomized clinical trial comparing ato-oxy versus endotype-directed treatment for OSA in children and adults with DS. We will enroll 200 participants with Down syndrome and OSA (100 children age 6-17 years, 100 adults age 18+ years). Participants will be recruited from five clinical sites from across the country as well as via outreach. Participants will be randomized 1:1 at an individual level to either ato-oxy or endotype-directed treatment, which would be either oxygen or ato-oxy dependent upon the individual's OSA endotype. The study primary outcome is obstructive apnea-hypopnea index, the primary measure of OSA severity. Secondary study outcomes include measures of HRQOL, behavior, cognition and adverse effects. Participants will receive treatment and be followed for a total of 12 months during the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Uniform therapy (ato-oxy) | Active comparator | Drug: ato-oxyAll participants receive the combination of atomoxetine and oxybutynin (ato-oxy) once nightly |
| Endotype Directed Treatment | Experimental | Drug: ato-oxy, Drug: OxygenParticipants 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). |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ato-oxyAlso: atomoxetine and oxybutynin0.5 mg/kg (max 40 mg) of atomoxetine and 5mg oxybutynin taken nightly. | Drug | Endotype Directed Treatment, Uniform therapy (ato-oxy) |
| OxygenOxygen via nasal cannula used nightly | Drug | Endotype Directed Treatment |
Primary outcome
obstructive apnea-hypopnea index (oAHI)
Time frame: 12 months
change in number of obstructive apneas and hypopneas per hour on polysomnography from baseline. Decreased oAHI indicates better outcome.
2 secondary outcomes
Change in caregiver Pediatric Quality of Life (PedsQL) score from baseline
Time frame: 12 months
Change in Paired Associate Learning test total adjusted errors from baseline
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2026.
- Background: PubMed 37555595Combs 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.
- Individual participant dataSharing planned: Yes. De-identified data will be made available.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Daniel Combs, MD principal investigator
University of Arizona
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing ato-oxy and Oxygen in people with Obstructive Sleep Apnea (OSA) and Down Syndrome, run by University of Arizona at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 3 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Natalie Provencio-Dean (520-403-6165, nataliep@arizona.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
obstructive apnea-hypopnea index (oAHI) (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07280468, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2026.