Atomoxetine + Oxybutynin for Sleep Apnea in Down Syndrome

(MOSAIC Trial)

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Arizona

Must not be taking: Monoamine oxidase inhibitors

Disqualifiers: Central sleep apnea, Seizure disorder, Congenital heart disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 6 months

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two medications, atomoxetine and oxybutynin, to determine if they can reduce sleep apnea in children with Down syndrome. Sleep apnea disrupts breathing during sleep, affecting restful nights. The study examines whether taking these medications before bedtime can improve sleep quality by reducing disruptions. Children with Down syndrome and diagnosed obstructive sleep apnea may qualify if they haven't used certain other treatments, such as positive airway pressure therapy. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to important findings.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using a monoamine oxidase inhibitor. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research is testing a combination of two medicines, atomoxetine and oxybutynin, to treat obstructive sleep apnea (OSA) in children with Down syndrome. A previous study showed that this combination significantly reduced the severity of OSA. The study also assessed safety and found the treatment generally well-tolerated, with no serious side effects reported.

Another study on adults with Down syndrome showed encouraging results, suggesting the treatment is likely safe for children too. Both atomoxetine and oxybutynin have approval for other uses, which reassures about their safety. While side effects can occur, they were not serious enough in these studies to halt the research. Overall, current evidence suggests this treatment is safe enough to continue studying. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sleep apnea in Down syndrome?

Researchers are excited about using atomoxetine and oxybutynin for sleep apnea in individuals with Down syndrome because these drugs offer a new approach by targeting the nervous system. While most treatments for sleep apnea, like CPAP machines, focus on keeping the airway open physically, atomoxetine and oxybutynin work by enhancing airway muscle tone and reducing airway collapse during sleep. Atomoxetine is a norepinephrine reuptake inhibitor, and oxybutynin has anticholinergic properties, both of which help improve muscle tone. This combination could provide a non-invasive treatment option that addresses the underlying muscle control issues in sleep apnea, particularly benefiting those with Down syndrome.

What evidence suggests that this treatment might be an effective treatment for sleep apnea in Down syndrome?

Research has shown that a combination of two medications, atomoxetine and oxybutynin, called ato-oxy, may help treat obstructive sleep apnea (OSA) in children with Down syndrome. Studies have found that this treatment significantly reduces the number of breathing interruptions during sleep by 72%, meaning children experienced fewer breathing problems while sleeping. Researchers have also tested the treatment in adults with Down syndrome, suggesting it might be beneficial for different age groups. This trial will evaluate the effectiveness of ato-oxy in managing sleep apnea in people with Down syndrome. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

Children aged 6-17 with Down syndrome and obstructive sleep apnea can join this trial. They must have a confirmed diagnosis of trisomy 21 Down syndrome, not due to translocation or mosaicism. Kids with untreated depression, hypothyroidism, severe prematurity, certain heart diseases without clearance, or those on specific medications like MAO inhibitors cannot participate.

Inclusion Criteria

I am between 6 and 17 years old.

I have been diagnosed with Down syndrome.

Exclusion Criteria

My tonsils are significantly enlarged.

You are pregnant, as confirmed by a urine test.

I have depression that I haven't treated yet.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive ato-oxy for 6 months, with dosing occurring approximately 30 minutes prior to bedtime

6 months

1 visit (in-person) for final night of dosing

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Atomoxetine and Oxybutynin (ato-oxy)

Trial Overview The study tests a combination medication called ato-oxy (atomoxetine and oxybutynin) given before bedtime for six months to see if it improves sleep apnea and cognition in children with Down syndrome. The effectiveness is measured by changes in the number of breathing pauses during sleep from the start to the end of treatment.

How Is the Trial Designed?

Group I: Ato-oxy Experimental Treatment 1 Intervention

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

Atomoxetine and Oxybutynin (ato-oxy) is already approved in United States, European Union for the following indications:

Approved in United States as Atomoxetine and Oxybutynin for:

• Attention Deficit Hyperactivity Disorder (atomoxetine)
• Overactive bladder (oxybutynin)
• Off-label use for Obstructive Sleep Apnea in children with Down syndrome

Approved in European Union as Atomoxetine and Oxybutynin for:

• Attention Deficit Hyperactivity Disorder (atomoxetine)
• Urinary incontinence and urgency (oxybutynin)
• Off-label use for Obstructive Sleep Apnea in children with Down syndrome

Who Is Running the Clinical Trial?

University of Arizona

Lead Sponsor

Trials

545

Recruited

161,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In a study involving 17 Japanese patients with obstructive sleep apnea (OSA), combination therapy with atomoxetine (ATO) and oxybutynin (OXY) did not significantly reduce the apnoea-hypopnoea index (AHI) compared to no medication, indicating limited overall efficacy.

However, a subset of five patients did show a notable decrease in AHI, suggesting that ATO-OXY therapy may benefit certain individuals, although the treatment did alter sleep architecture by increasing light sleep (N1) and decreasing deeper sleep stages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of the combination of atomoxetine and oxybutynin in Japanese patients with obstructive sleep apnoea: A randomized controlled crossover trial. Kinouchi, T., Terada, J., Sakao, S., et al.[2023]

The combination of atomoxetine and trazodone (Ato-Trazo) significantly reduced the apnea-hypopnea index in patients with obstructive sleep apnea (OSA), indicating improved severity of the condition, with a reduction from 18.2 to 7.4 events per hour (P = .024).

Unlike previous treatments, Ato-Trazo did not lower the arousal threshold, suggesting it may be better tolerated by patients, although it worsened self-reported sleep quality and further studies are needed to optimize dosage and identify the best patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of atomoxetine plus a hypnotic on obstructive sleep apnea severity in patients with a moderately collapsible pharyngeal airway. Corser, B., Eves, E., Warren-McCormick, J., et al.[2023]

A study using Taiwan's National Health Insurance Research Database found that long-term use of the atomoxetine-oxybutynin combination (AOC) is associated with a significantly reduced risk of developing obstructive sleep apnea (OSA), with an adjusted hazard ratio of 0.299 for those using AOC for over a year.

The incidence of OSA was lower in patients using AOC (21.92 per 100,000 person-years) compared to those not using it (22.93 per 100,000 person-years), suggesting that this combination therapy may effectively lower OSA risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term atomoxetine-oxybutynin combination use may be beneficial for the prevention of obstructive sleep apnea. Chen, TY., Chung, CH., Chang, HA., et al.[2021]

In a randomized, double-blind, placebo-controlled study involving patients with mild to moderate obstructive sleep apnea, the new drug aroxybutynin (AD109) significantly reduced hypoxic burden and apnea-hypopnea index compared to placebo, indicating its efficacy in treating this condition.

AD109 demonstrated a favorable safety profile, suggesting it may be a promising pharmacological option for patients who struggle with adherence to traditional therapies for obstructive sleep apnea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of atomoxetine with the novel antimuscarinic aroxybutynin improves mild to moderate OSA. Rosenberg, R., Abaluck, B., Thein, S.[2023]

In a clinical trial involving 15 children with Down syndrome and obstructive sleep apnea, the combination of atomoxetine and oxybutynin (ato-oxy) significantly reduced the obstructive apnea-hypopnea index, indicating improved sleep quality.

While the treatment showed promise in reducing apnea events, it did not significantly improve health-related quality of life scores or sleep architecture, and the most common side effects were mild irritability and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The combination of atomoxetine and oxybutynin for the treatment of obstructive sleep apnea in children with Down syndrome. Combs, D., Edgin, J., Hsu, CH., et al.[2023]

In a phase 2 trial involving 62 patients with obstructive sleep apnea (OSA), the combination treatment AD036 (atomoxetine 80 mg and oxybutynin 5 mg) significantly reduced the apnea-hypopnea index (AHI) from a median of 14.2 events/hour on placebo to 6.2 events/hour, indicating a marked improvement in OSA severity.

AD036 not only improved OSA severity but also reduced the oxygen desaturation index and hypoxic burden, while atomoxetine alone showed some benefits but was associated with more sleep disruption, suggesting that oxybutynin may help mitigate these effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of atomoxetine plus oxybutynin in the treatment of obstructive sleep apnea with moderate pharyngeal collapsibility. Schweitzer, PK., Maynard, JP., Wylie, PE., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37555595/

The combination of atomoxetine and oxybutynin for ... - PubMed We evaluated the effectiveness of atomoxetine and oxybutynin (ato-oxy) to treat OSA in children with Down syndrome.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10692944/

The combination of atomoxetine and oxybutynin for the ... The combination of atomoxetine and oxybutynin is a promising treatment for obstructive sleep apnea in adults with Down syndrome and may be particularly ...

3. jcsm.aasm.org jcsm.aasm.org/doi/abs/10.5664/jcsm.10764

The combination of atomoxetine and oxybutynin for the ... We evaluated the effectiveness of atomoxetine and oxybutynin (ato-oxy) to treat OSA in children with Down syndrome.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04115878?tab=results

Study Results | NCT04115878 | Medications for Obstructive ... ... 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.

5. frontiersin.org frontiersin.org/journals/sleep/articles/10.3389/frsle.2025.1682625/pdf

Efficacy of atomoxetine and oxybutynin in the treatment ... There was a great improvement in the Apnea and Hypopnea. Index (AHI) measured with polysomnography with a reduction of. 72% (AHI 30.4 events/h ...

6. academic.oup.com academic.oup.com/sleep/article/46/Supplement_1/A351/7182500

0796 Safety and efficacy of the combination of atomoxetine ... Children with Down syndrome (DS) are at very high risk for obstructive sleep apnea (OSA), with a prevalence of OSA of 50-79%.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02908529

Atomoxetine and Oxybutynin in Obstructive Sleep Apnea The combination of atomoxetine and oxybutynin greatly reduces obstructive sleep apnea severity. A randomized, placebo-controlled, double-blind crossover trial.