CFD Simulations for Pediatric Sleep Apnea

(OSA-MRI Trial)

Overseen By Carrie Stevens

Age: < 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Children's Hospital Medical Center, Cincinnati

Disqualifiers: Adequately treated with CPAP, braces, 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: Unknown

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to develop a computer tool that predicts surgical outcomes for children with obstructive sleep apnea (OSA), a condition where breathing stops and starts during sleep. Traditional surgeries, such as tonsil removal, often don't fully cure OSA, and many children cannot tolerate other treatments like CPAP machines. By using advanced imaging and computer simulations, the trial seeks to identify the best surgical options for each child. It is suitable for children aged 3-18 who still have moderate to severe OSA after tonsil removal and may need further surgery. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, helping to understand how it benefits more patients.

Do I have to stop taking my current medications for the trial?

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

What is the safety track record for this technique?

Research has shown that hyperpolarized xenon 129 (129Xe) is a safe and well-tolerated gas for children to inhale during MRI scans. Studies have found it can be used without major problems, even in children with cystic fibrosis, a lung condition, making it a good option for lung imaging.

However, researchers continue to study its safety, especially in very young children. Most current data supports its use in children aged 6 to 12 years. While generally considered safe, parents should know that it remains relatively new for some age groups.

Overall, 129Xe has proven both practical and safe for use in children, reassuring those considering participation in clinical trials involving this gas. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it leverages advanced Computational Fluid Dynamics (CFD) to enhance our understanding of pediatric obstructive sleep apnea, a condition typically managed with CPAP machines or surgery. Unlike current treatments that focus on symptom relief, this approach aims to provide a detailed analysis of the airway dynamics using cutting-edge MRI techniques with inhaled gas contrast. By capturing precise anatomical and airflow data, this method could lead to more personalized and effective treatment strategies, potentially improving surgical outcomes and tailoring CPAP therapy.

What evidence suggests that this computational tool is effective for improving outcomes in pediatric obstructive sleep apnea?

Research has shown that computer simulations might improve surgery outcomes for children with obstructive sleep apnea (OSA). In this trial, one group will use real-time MRI scans with hyperpolarized xenon-129 to observe airway movement, creating a more accurate picture. Early results suggest this method can help doctors select the best surgery for each child. Studies have confirmed that using hyperpolarized xenon-129 in MRI scans is safe and comfortable for children. These scans provide detailed images of airflow, aiding doctors in understanding and enhancing treatment. Overall, these advancements could make surgeries more effective for children with OSA. ^{6 7 8 9 10}

Who Is on the Research Team?

Alister Bates, PhD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Are You a Good Fit for This Trial?

This trial is for children aged 5-18 with obstructive sleep apnea (OSA) who haven't improved after tonsil and adenoid removal, or those who can't tolerate CPAP therapy. It's also open to kids needing surgery for OSA as per a surgeon's assessment. Kids with braces/metal rods, well-managed on CPAP, or unable to undergo MRI are excluded.

Inclusion Criteria

I may have a blocked airway due to issues like a large tongue or small jaw.

My parents chose surgery for me without trying CPAP first.

I am either male or female.

Exclusion Criteria

My child cannot have sedatives due to health reasons.

Standard MRI exclusion criteria as set forth by the CCHMC Department of Radiology

My child is successfully treated with CPAP.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Data Collection Pre-Surgery

Collect data characterizing upper airway anatomy, motion, and airflow using MRI and other measurements

4 weeks

Multiple visits for imaging and data collection

Surgical Intervention and Post-Surgery Data Collection

Perform surgical interventions and collect post-surgery data to assess changes in airway anatomy and function

12 weeks

Multiple visits for surgery and follow-up imaging

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Regular follow-up visits for monitoring

What Are the Treatments Tested in This Trial?

Interventions

• 129-Xe
• Improving Outcomes in Pediatric Obstructive Sleep Apnea With Computational Fluid Dynamics

Trial Overview The study aims to develop a computational tool using Computational Fluid Dynamics (CFD) simulations based on real-time MRI data. This tool will predict which surgical options might best improve pediatric OSA by modeling airflow in the upper airways more accurately than previous methods.

How Is the Trial Designed?

Group I: Phase 2 - Contrast 129Xe MRI ages 3-18 Experimental Treatment 1 Intervention

The research team plans to collect data characterizing upper airway anatomy, motion, and airflow. In patients, these data may be recorded before and after surgery. The data may include some or all of the following: (1) Static and dynamic proton MRI of the airway. (2) Respiratory airflow measurements. (3) Data from clinical PSGs. (5) Measurements may be repeated at different levels of CPAP.

Group II: Phase 1 - Contrast 129Xe MRI ages 5-18 Experimental Treatment 1 Intervention

The research team will collect data characterizing upper airway anatomy, motion, and airflow. In patients, these data may be recorded before and after surgery. The data may include some or all of the following: (1) Static and dynamic proton MRI of the airway. (2) Respiratory airflow measurements. (3) Phase contrast MRI of inhaled gas. (4) Data from clinical PSGs. (5) Measurements may be repeated at different levels of CPAP.

Improving Outcomes in Pediatric Obstructive Sleep Apnea With Computational Fluid Dynamics is already approved in United States, European Union for the following indications:

Approved in United States as Tonsillectomy and Adenoidectomy for:

• Pediatric Obstructive Sleep Apnea

Approved in United States as CPAP and BPAP for:

• Pediatric Obstructive Sleep Apnea
• Moderate to Severe Sleep Apnea

Approved in European Union as Tonsillectomy and Adenoidectomy for:

• Pediatric Obstructive Sleep Apnea

Approved in European Union as CPAP and BPAP for:

• Pediatric Obstructive Sleep Apnea
• Moderate to Severe Sleep Apnea

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

Adenotonsillectomy, the main surgical treatment for obstructive sleep apnea (OSA) in children, is only effective in about 50% of obese children, highlighting the need for better patient selection.

Using computational fluid dynamics to model airway flow before and after surgery can help identify which obese children are more likely to benefit from adenotonsillectomy, potentially improving surgical outcomes and reducing health risks associated with OSA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Computational modeling of upper airway before and after adenotonsillectomy for obstructive sleep apnea. Mihaescu, M., Murugappan, S., Gutmark, E., et al.[2008]

A computational fluid dynamics (CFD) study involving three children with obstructive sleep apnea syndrome (OSAS) revealed that airway geometry significantly influences internal pressure distribution, particularly during breathing.

In children with OSAS, the pressure drop during inspiration occurs mainly in the area where the adenoids and tonsils overlap, indicating that airway narrowing in this region is critical, while in healthy controls, most pressure loss happens in the nasal passages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Computational fluid dynamics modeling of the upper airway of children with obstructive sleep apnea syndrome in steady flow. Xu, C., Sin, S., McDonough, JM., et al.[2013]

In a study of 68 children with symptoms of obstructive sleep apnea (OSA), those with moderate-to-severe OSA showed significantly higher airway pressure, resistance, and velocity compared to those with primary snoring, indicating distinct airway characteristics associated with OSA.

The study suggests that computational fluid dynamics (CFD) can effectively evaluate upper airway patency in children, with specific cut-off points for airway pressure, resistance, and velocity that may help identify moderate-to-severe OSA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Computational fluid dynamics study in children with obstructive sleep apnea. Hsu, WC., Kang, KT., Chen, YJ., et al.[2023]

In a study involving 10 patients with Down syndrome and persistent obstructive sleep apnea, virtual surgery using computational fluid dynamics showed promise in assessing airflow changes and upper airway resistance, indicating a potential new method for surgical planning.

Actual surgeries were successful in treating 6 out of 10 patients, and in 8 of 10 subjects, both the apnea-hypopnea index and upper airway resistance improved after virtual surgery, suggesting that this approach could help identify effective surgical interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Computational Modeling of Airway Obstruction in Sleep Apnea in Down Syndrome: A Feasibility Study. Mylavarapu, G., Subramaniam, D., Jonnagiri, R., et al.[2018]

A study involving 7 adult patients with obstructive sleep apnea (OSA) used 3D models from CT scans and computational fluid dynamics (CFD) simulations to analyze upper airway flow characteristics.

The research found a strong correlation (Pearson's r = 0.91) between a CFD parameter and the apnea-hypopnea index, suggesting that this method could help assess OSA severity by providing detailed functional insights into the upper airways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of human obstructive sleep apnea using computational fluid dynamics. Taherian, S., Rahai, H., Lopez, S., et al.[2023]

A computer simulation model based on the specific anatomy of four obstructive sleep apnea (OSA) patients effectively predicted the percentage and sites of upper airway collapse, showing strong agreement with findings from drug-induced sleep endoscopy (DISE).

This innovative modeling approach suggests that personalized simulations could be a valuable tool in guiding surgical interventions for OSA, potentially improving treatment outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Constructing a patient-specific computer model of the upper airway in sleep apnea patients. Dhaliwal, SS., Hesabgar, SM., Haddad, SMH., et al.[2018]

Computational models of the upper airway can predict how different surgical manipulations, like palatal and tongue stiffening, affect pharyngeal mechanics in patients with obstructive sleep apnea (OSA).

These models, developed from MRI images and muscle activity measurements, suggest that personalized treatment strategies for OSA could be improved by understanding individual anatomical variations and their impact on airway collapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of computational modeling to predict responses to upper airway surgery in obstructive sleep apnea. Huang, Y., White, DP., Malhotra, A.[2018]

Citations

1. clinicaltrial.be clinicaltrial.be/en/details/40915?per_page=20&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Improving Outcomes in Pediatric Obstructive Sleep Apnea W... This project aims to create a validated computational tool to predict surgical outcomes for pediatric patients with obstructive sleep apnea (OSA).

2. scienceblog.cincinnatichildrens.org scienceblog.cincinnatichildrens.org/advancements-in-specialized-imaging-create-innovative-airway-assessment-tool/

Advancements in Specialized Imaging Create Innovative ... This is the first study to use PC-MRI of inhaled hyperpolarized xenon in pediatric patients with OSA. Findings include: Proton MRI highlights ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9519191/

Pediatric 129Xe Gas-Transfer MRI – Feasibility and Applicability The inhalation of hyperpolarized 129Xe gas for breath-hold MRI has been shown to be safe and well tolerated in adults and children for ventilation and diffusion ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02272049?term=AREA%5BBasicSearch%5D(xenon%20Xe%20129%20hyperpolarized)&rank=1

Study Details | Use of Hyperpolarized Xenon Gas for Lung ... A type of clinical study in which participants are identified as belonging to study groups and are assessed for biomedical or health outcomes. Participants may ...

5. mdpi.com mdpi.com/2075-4418/15/4/474

Hyperpolarized Xenon-129 MRI: Narrative Review of ... XeMRI may likewise be more effective than FEV1 at differentiating patients with CF from healthy controls, particularly in pediatric patients, and has been shown ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5083137/

Feasibility, tolerability and safety of pediatric hyperpolarized ... Hyperpolarized 129Xe is a safe and well-tolerated inhaled contrast agent for pulmonary MR imaging in healthy children and in children with cystic fibrosis who ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/214375Orig1s000lbl.pdf

XENOVIEW (xenon Xe 129 hyperpolarized), for oral inhalation Although supportive safety data are available for pediatric patients 6 years to less than 12 years of age. [see Adverse Reactions (6.1)], use of XENOVIEW is not ...

8. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/ppul.27410

Xe Ventilation and Gas‐Exchange MRI Abnormalities in ... Despite its safety and feasibility in the pediatric population, the use of this novel imaging technique has not been as well-described in chILD.

9. mayoclinic.org mayoclinic.org/drugs-supplements/xenon-xe-129-hyperpolarized-inhalation-route/description/drg-20543669

Xenon xe 129 hyperpolarized (inhalation route) Safety and efficacy have not been established. Geriatric. Appropriate studies performed to date have not demonstrated geriatric-specific ...

10. clinicaltrials.gov clinicaltrials.gov/study/NCT02272049

Study Details | Use of Hyperpolarized Xenon Gas for Lung ... The goal of this study is to evaluate the usefulness of hyperpolarized (HP) 129Xe (xenon) gas MRI for regional assessment of lung function in a normal ...