Oxygen Therapy for Down Syndrome with Sleep Apnea

(DOSA Trial)

Recruiting at 6 trial locations

Overseen By Raouf Amin, MD

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Brigham and Women's Hospital

Must not be taking: Pulmonary vasodilators

Disqualifiers: CPAP use, 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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 6 months

230 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess whether oxygen supplementation during sleep improves working memory and other clinical and patient-reported outcomes among children who have Down Syndrome (DS) with moderate to severe Obstructive Sleep Apnea (OSA).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the study team or your doctor.

What data supports the effectiveness of the treatment Oxygen, O2, for Down Syndrome with Sleep Apnea?

Supplemental oxygen has been shown to improve oxygenation and reduce breathing difficulties during sleep in children with obstructive sleep apnea, suggesting it might be beneficial for those with Down syndrome and similar conditions. ^{1 2 3 4 5}

Is oxygen therapy safe for children with sleep apnea?

Research suggests that supplemental oxygen might be a safe and beneficial temporary treatment for children with obstructive sleep apnea, as it improves oxygen levels and reduces breathing issues during sleep. However, it may also affect the body's natural response to low oxygen, so careful monitoring is important. ^{2 5 6 7 8}

How is oxygen therapy unique for treating sleep apnea in Down syndrome?

Oxygen therapy is unique for treating sleep apnea in Down syndrome because it provides supplemental oxygen directly, which can be beneficial for those who may not tolerate other treatments like CPAP (continuous positive airway pressure) or surgery. It is a non-invasive option that can be used when other treatments are not suitable or effective. ^{5 9 10 11 12}

Research Team

Susan Redline

Principal Investigator

Brigham and Women's Hospital

Raouf Amin

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Eligibility Criteria

This trial is for children and teens aged 5 to 17.9 with Down Syndrome who have moderate to severe Obstructive Sleep Apnea (OSA). They should be able to perform neuropsychological tests, not use CPAP regularly or take supplemental oxygen, and must not have other severe chronic diseases or untreated hypothyroidism.

Inclusion Criteria

My child has moderate to severe sleep apnea.

At baseline, the participant attempts to perform the neuropsychological tests

I am willing and able to follow all study rules and attend all appointments.

Exclusion Criteria

You currently use a CPAP machine for sleep apnea and use it for at least 4 hours every night.

Your oxygen level is less than 90% when you are awake and not active.

Someone smokes in the child's bedroom.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Baseline data collection including demographic data, neurocognitive testing, echocardiography, physical examination, and venipuncture

1-2 weeks

1 visit (in-person)

Treatment

Participants receive nocturnal oxygen therapy and supportive care materials for 6 months

6 months

2 visits (in-person), 1 visit (virtual) at 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including repeat of baseline studies and PSG

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Oxygen

Trial Overview The study is testing if giving extra oxygen during sleep can help improve working memory and other outcomes in kids with Down Syndrome who also suffer from OSA. The oxygen flow won't exceed certain limits, ensuring safety.

Participant Groups

Group I: Oxygen plus supportive care (OXT) Active Control 1 Intervention

Nocturnal oxygen therapy plus providing patient with healthy sleep habits materials, healthy diet materials and nasal dilators.

Group II: Supportive care (SC) Active Control 1 Intervention

Providing patient with healthy sleep habits materials, healthy diet materials and nasal dilators.

Oxygen is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Oxygen for:

• General anesthesia
• Respiratory distress
• Cardiac arrest
• Hypoxia

Approved in European Union as Oxygen for:

• General anesthesia
• Respiratory distress
• Cardiac arrest
• Hypoxia

Approved in Canada as Oxygen for:

• General anesthesia
• Respiratory distress
• Cardiac arrest
• Hypoxia

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Rainbow Babies and Children's Hospital

Collaborator

Trials

9

Recruited

4,000+

University of Southern California

Collaborator

Trials

956

Recruited

1,609,000+

University of Michigan

Collaborator

Trials

1,891

Recruited

6,458,000+

Children's Hospital of Philadelphia

Collaborator

Trials

749

Recruited

11,400,000+

Children's Hospital Medical Center, Cincinnati

Collaborator

Trials

844

Recruited

6,566,000+

Children's Hospital Los Angeles

Collaborator

Trials

257

Recruited

5,075,000+

Children's Hospital of The King's Daughters

Collaborator

Trials

14

Recruited

12,000+

Seattle Children's Hospital

Collaborator

Trials

319

Recruited

5,232,000+

Findings from Research

In a study of 18,181 patients with Down syndrome, those aged 6 and older had significantly higher odds of developing Obstructive Sleep Apnea (OSA), with odds ratios ranging from 3.4 to 3.6 compared to younger patients.

Hypertrophied tonsils and adenoids were identified as the strongest risk factors for OSA, with an odds ratio of 64.2 when both conditions were present, highlighting the importance of monitoring these conditions in Down syndrome patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What are the Soft Tissue Risk Factors for Obstructive Sleep Apnea in Patients with Down's Syndrome? Stanbouly, D., Steinberg, B., Chuang, SK.[2023]

In a study of 16 children aged 2-8 with obstructive sleep apnea syndrome (OSAS), supplemental oxygen significantly improved oxygen levels during sleep, raising average SpO2 from 89.5% to 97.7%.

The use of supplemental oxygen also led to a reduction in hypopnea density and obstructive apnea index, while maintaining stable ventilation, suggesting it may be a safe and effective temporary treatment for children with OSAS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of overnight supplemental oxygen in obstructive sleep apnea in children. Aljadeff, G., Gozal, D., Bailey-Wahl, SL., et al.[2013]

A new aggressive surgical approach for treating obstructive sleep apnea in children with Down syndrome showed significant improvement, with the apnea index dropping from a mean of 34.00 preoperatively to 1.62 postoperatively, indicating effective management of the condition.

All seven children in the study experienced symptomatic improvement, although one patient faced complications leading to a tracheostomy, highlighting the need for careful preoperative evaluation, including cardiac assessments, in this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Down syndrome: identification and surgical management of obstructive sleep apnea. Lefaivre, JF., Cohen, SR., Burstein, FD., et al.[2019]

In a study of 19 young patients with Down syndrome, 79% were found to have obstructive sleep apnea (OSA), indicating a high prevalence of this condition in this population.

The study revealed significant associations between OSA and factors such as higher body mass index, age, and poor sleep quality, highlighting the need for further research to improve treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective polysomnographic analysis of obstructive sleep apnea in down syndrome. Dyken, ME., Lin-Dyken, DC., Poulton, S., et al.[2013]

In a study of 24 children with Down syndrome and mild obstructive sleep apnea (OSA), treatment with nasal steroids, oral anti-leukotrienes, or supplemental oxygen did not significantly improve sleep apnea severity as measured by the obstructive apnea-hypopnea index (oAHI) or other polysomnographic outcomes.

Only a small percentage of children experienced resolution of OSA after treatment (20% with medication, 7.7% with observation, and 0% with oxygen), indicating that multimodal treatment approaches may be necessary for effective management in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes in children with down syndrome and mild obstructive sleep apnea treated non-surgically. Howard, JJM., Sarber, KM., Yu, W., et al.[2021]

Long-term nocturnal oxygen therapy (LTOT) is safe and well-accepted in children with sickle cell disease (SCD) and chronic hypoxaemia, with no major adverse events reported during the study of 19 children.

After one year of LTOT, improvements were observed in oxygen saturation levels during overnight oximetry tests, indicating enhanced oxygen delivery without significant changes in hemoglobin levels or vaso-occlusive pain events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term oxygen therapy in children with sickle cell disease and hypoxaemia. Liguoro, I., Arigliani, M., Singh, B., et al.[2021]

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]

Oxygen therapy significantly improves oxygen saturation levels in patients with obstructive sleep apnea (OSA), as shown in a systematic review of 14 studies involving 359 patients.

Despite the benefits in oxygen saturation, O2 therapy may lead to longer durations of apnea and hypopnea episodes compared to placebo, indicating a potential trade-off in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obstructive sleep apnea and oxygen therapy: a systematic review of the literature and meta-analysis. Mehta, V., Vasu, TS., Phillips, B., et al.[2021]

Upper airway stimulation was found to be a safe and effective treatment for 42 adolescents with Down syndrome and severe obstructive sleep apnea (OSA), showing a significant mean decrease in the apnea-hypopnea index (AHI) by 12.9 events/hour after 12 months.

The treatment resulted in a 65.9% response rate, with many patients experiencing improved quality of life and minimal complications, primarily temporary oral discomfort in 11.9% of cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Upper Airway Stimulation for Adolescents With Down Syndrome and Obstructive Sleep Apnea. Yu, PK., Stenerson, M., Ishman, SL., et al.[2023]

Individuals with Down syndrome (DS) have a higher prevalence and severity of obstructive sleep apnea (OSA), necessitating routine screening for all DS patients due to the potential for serious health consequences.

Polysomnography is the gold standard for diagnosing OSA in DS, and treatment options include adenotonsillectomy and CPAP, with emerging therapies like hypoglossal nerve stimulation showing promise for difficult cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obstructive sleep apnea in patients with Down syndrome: current perspectives. Simpson, R., Oyekan, AA., Ehsan, Z., et al.[2020]

In a study of 17 adults with Down syndrome (DS) and obstructive sleep apnea (OSA), CPAP treatment showed good long-term compliance, with 81.2% of DS patients using it effectively, similar to the 78.9% compliance in age-matched controls.

Patients with DS reported significantly higher subjective CPAP usage (8 hours) compared to controls (6.75 hours), indicating that they can adapt well to CPAP therapy, making them suitable candidates for future clinical trials aimed at preventing Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and Long-Term Compliance to Continuous Positive Airway Pressure Treatment in Adults With Down Syndrome, a Genetic Form of Alzheimer's Disease. Giménez, S., Farre, A., Morente, F., et al.[2022]

In a study of 57 children with Down syndrome, 80% were found to have obstructive sleep apnea (OSA), with 39% experiencing severe cases (AHI ≥10 events/hr).

Noninvasive respiratory support was effective in treating OSA, showing good compliance among patients, with an average nightly use of nearly 9 hours, and it improved nocturnal gas exchange in most cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obstructive sleep apnea in Down syndrome: Benefits of surgery and noninvasive respiratory support. Dudoignon, B., Amaddeo, A., Frapin, A., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

What are the Soft Tissue Risk Factors for Obstructive Sleep Apnea in Patients with Down's Syndrome? [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Effects of overnight supplemental oxygen in obstructive sleep apnea in children. [2013]

3. United States pubmed.ncbi.nlm.nih.gov

Down syndrome: identification and surgical management of obstructive sleep apnea. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Prospective polysomnographic analysis of obstructive sleep apnea in down syndrome. [2013]

5. United States pubmed.ncbi.nlm.nih.gov

Outcomes in children with down syndrome and mild obstructive sleep apnea treated non-surgically. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Long-term oxygen therapy in children with sickle cell disease and hypoxaemia. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

The combination of atomoxetine and oxybutynin for the treatment of obstructive sleep apnea in children with Down syndrome. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Obstructive sleep apnea and oxygen therapy: a systematic review of the literature and meta-analysis. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Evaluation of Upper Airway Stimulation for Adolescents With Down Syndrome and Obstructive Sleep Apnea. [2023]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Obstructive sleep apnea in patients with Down syndrome: current perspectives. [2020]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Feasibility and Long-Term Compliance to Continuous Positive Airway Pressure Treatment in Adults With Down Syndrome, a Genetic Form of Alzheimer's Disease. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Obstructive sleep apnea in Down syndrome: Benefits of surgery and noninvasive respiratory support. [2020]