Oxygen Versus Medical Air for Treatment of CSA in Prader Will Syndrome

Study Overview
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Brief Summary
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The aim of this study is to determine if treatment with Medical Air (21% oxygen in room air) compared to supplemental oxygen (100% oxygen) will lead to similar improvements in the central apnea-hypopnea index (CAHI) for infants with Prader-Willi Syndrome. Despite the vast amount of research investigating the cause of central sleep apnea, there remain gaps in knowledge, lending to further research efforts. The decision to compare oxygen to medical air is based on several theorized mechanisms. The first of which is the supposition that provision of medical air may act as an arousal stimulus for the hypothalamus, thereby preventing sleep disordered breathing. Secondly, the hypercapnic challenge performed by Livingston et al demonstrated a delayed hypercapneic arousal response in PWS subjects despite simultaneous hyperoxia, leading us to question if therapeutic oxygen really plays a significant role in treating CSA. Lastly, the delivery of medical air via nasal prongs may provide sufficient arousal to terminate the cycle of events leading to central apnea, as described by Urquhart et al. A deeper understanding of central sleep apnea is essential to ameliorating its adverse sequelae, which include symptoms of ADHD, impaired attention, behavioral problems, and academic difficulties.

Official Title
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Comparison of Therapeutic Oxygen Versus Medical Air for the Treatment of Central Sleep Apnea in Infants and Children With Prader Willi Syndrome: A Proof of Concept Study

Conditions
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Sleep Apnea, Central, Prader-Willi Syndrome

Intervention / Treatment
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* Biological: Medical Air vs Oxygen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: infants under age two with genetically confirmed Prader-Willi Syndrome referred to HSC sleep clinic for evaluation with polysomnogram prior to initiation of growth hormone infants found to have clinically significant central sleep apnea, defined as an apnea-hypopnea index (AHI) equal to or greater than 5 Exclusion Criteria: infants delivered prematurely (less than 37 weeks gestational age) term infants with a history of hypoxic-ischemic encephalopathy or stroke any concurrent diagnoses that may cause sleep-disordered breathing (ie. craniofacial abnormalities, arnold-chiari malformation, etc) infants with a need for daytime supplemental oxygen (ie. cardiac anomalies) infants found to have low baseline oxygen saturations on PSG

Ages Eligible for Study
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Maximum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The screening visit will occur during a regularly scheduled clinic visit. The patients that have consented for the study will all undergo the baseline PSG. Only patients with clinically significant CSA after Visit 1 will undergo randomization and complete Visit 2. Those who have a CAHI greater or equal to 5 will be randomly assigned to Arm A or Arm B. Randomization will be performed using a computer with random numbers drawn. Arm A will receive Medical Air followed by Oxygen and Arm B will receive Oxygen followed by Medical Air.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Medical air followed by oxygen<br> | Biological: Medical Air vs Oxygen<br>* Medical Air/Oxygen will be given<br>|
| Experimental: Arm B: Oxygen followed by medical air<br> | Biological: Medical Air vs Oxygen<br>* Medical Air/Oxygen will be given<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delta CAHI1 | Difference in CAHI at baseline compared to supplemental oxygen Delta CAHI1: CAHIoxygen - CAHIbaseline | 2 years | 
| Delta CAHI2 | Difference in CAHI at baseline compared to medical air Delta CAHI2: CAHImedical air - CAHIbaseline | 2 years | 
| Difference in CAHI1 and CAHI2 | A comparison of change in CAHI1 and change in CAHI2 DeltaCAHI1: DeltaCAHI2 | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Arousal Index1 | Difference in Arousal Index at baseline compared to medical air Delta Arousal Index: Arousal Indexmedical air - Arousal Indexbaseline | 2 years | 
| Arousal Index2 | Difference in Arousal Index at baseline compared to Supplemental oxygen Delta Arousal Index: Arousal Indexoxygen - Arousal Indexbaseline | 2 years | 
| Desaturation Index1 | Difference in Desaturation Index at baseline compared to medical air Delta Arousal Index: Desaturation Indexmedical air - Desaturation Indexbaseline | 2 years | 
| Desaturation Index2 | Difference in Desaturation Index at baseline compared to supplemental oxygen Delta Arousal Index: Desaturation Indexoxygen - Desaturation Indexbaseline | 2 years |