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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if nighttime oxygen can improve working memory and other outcomes in children with Down Syndrome who have moderate to severe sleep apnea. Participants will either receive oxygen therapy (O2) along with guidance on healthy sleep habits and diet, or just the guidance without oxygen. The study seeks children diagnosed with sleep apnea who respond favorably to oxygen therapy. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that oxygen therapy is likely to be safe for children with Down Syndrome and sleep apnea?

Research has shown that oxygen therapy is generally safe for people with Down Syndrome who have obstructive sleep apnea. In one study involving adults with Down Syndrome and sleep apnea, participants experienced a noticeable reduction in pauses in breathing during sleep. This suggests that oxygen therapy can be effective without causing serious side effects.

Another study focused on children with sleep apnea and found that oxygen therapy improved their nighttime breathing. Although detailed safety information specifically for children with Down Syndrome is limited, these studies are promising and suggest that oxygen therapy is both safe and beneficial. The current trial is in its early stages, and existing safety data supports testing it in new situations like this one. ^{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 oxygen therapy for treating Down syndrome with sleep apnea because it offers a novel and potentially more effective approach compared to standard treatments like CPAP machines or lifestyle changes alone. Oxygen therapy provides nocturnal oxygen, which could directly improve breathing during sleep, addressing the root cause of sleep apnea more effectively. Additionally, the combination of oxygen therapy with supportive care materials, such as healthy sleep habits and diet guidance, may enhance overall treatment outcomes, offering a comprehensive approach that goes beyond traditional methods.

What evidence suggests that oxygen therapy might be an effective treatment for Down Syndrome with sleep apnea?

Research has shown that oxygen therapy can help treat obstructive sleep apnea (OSA) in children with Down Syndrome. In one study, all children experienced over a 50% decrease in their apnea-hypopnea index, which measures how often breathing stops during sleep, and their blood oxygen levels improved. Other studies have found that extra oxygen can help manage mild OSA in children by reducing breathing interruptions. In this trial, one group of participants will receive oxygen therapy alongside supportive care, while another group will receive supportive care alone. This approach suggests that oxygen therapy might improve sleep quality and daytime functioning in children with Down Syndrome who have moderate to severe OSA. ^{1 3 4 6 7}

Who Is on the Research Team?

Susan Redline

Principal Investigator

Brigham and Women's Hospital

Raouf Amin

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Are You a Good Fit for This Trial?

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.

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

At baseline, the participant attempts to perform the neuropsychological tests

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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 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]

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]

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]

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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7996085/

Outcomes in Children with Down Syndrome and Mild ... Nasal steroids, oral anti-leukotrienes and supplemental oxygen are effective in the treatment of mild obstructive sleep apnea (OSA) in otherwise healthy ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06043440?term=AREA%5BBasicSearch%5D(SB5)&rank=9

NCT06043440 | Down Syndrome Obstructive Sleep Apnea The purpose of this study is to assess whether oxygen supplementation during sleep improves working memory and other clinical and patient-reported outcomes ...

3. academic.oup.com academic.oup.com/sleep/article/48/Supplement_1/A343/8135939

0791 Oxygen Therapy for Children with Obstructive Sleep ... The aim of this study is to evaluate the effectiveness of oxygen therapy in children >1 year old with OSA and factors that influence the response to oxygen.

4. jcsm.aasm.org jcsm.aasm.org/doi/10.5664/jcsm.11452

Adults with Down syndrome and obstructive sleep apnea ... All patients experienced a > 50% decrease in apnea-hypopnea index and to less than 15 events/h. Median time spent below 88% improved from 2.0% (0.3, 5.0) to 0.2 ...

5. research.chop.edu research.chop.edu/down-syndrome-and-sleep-apnea-study-dosa

Down Syndrome and Sleep Apnea Study (DOSA) This research study is being conducted to look at oxygen as a treatment of obstructive sleep apnea (OSA) in children with Down syndrome.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11795284/

Respiratory support in patients with Down syndrome We systematically reviewed articles providing indications, benefits, adherence and limits of long-term NIV use in the paediatric and adult population with DS.

7. jamanetwork.com jamanetwork.com/journals/jamaotolaryngology/fullarticle/2791446

Upper Airway Stimulation for Adolescents With Down ... This study suggests that upper airway stimulation is a novel therapy that appears to be safe and effective for adolescent patients with Down syndrome and ...