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

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

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.

Study Overview

• Status: Completed
• Conditions: Prader-Willi Syndrome; Sleep Apnea, Central
• Intervention / Treatment: Biological: Medical Air vs Oxygen

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 2 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. infants under age two with genetically confirmed Prader-Willi Syndrome
2. referred to HSC sleep clinic for evaluation with polysomnogram prior to initiation of growth hormone
3. infants found to have clinically significant central sleep apnea, defined as an apnea-hypopnea index (AHI) equal to or greater than 5

Exclusion Criteria:

1. infants delivered prematurely (less than 37 weeks gestational age)
2. term infants with a history of hypoxic-ischemic encephalopathy or stroke
3. any concurrent diagnoses that may cause sleep-disordered breathing (ie. craniofacial abnormalities, arnold-chiari malformation, etc)
4. infants with a need for daytime supplemental oxygen (ie. cardiac anomalies)
5. infants found to have low baseline oxygen saturations on PSG

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Medical air followed by oxygen	Biological: Medical Air vs Oxygen; Medical Air/Oxygen will be given
Experimental: Arm B: Oxygen followed by medical air	Biological: Medical Air vs Oxygen; Medical Air/Oxygen will be given

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Investigators: Principal Investigator: Reshma Amin, MD, The Hospital for Sick Children

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2016
• Primary Completion (Actual): March 15, 2025
• Study Completion (Actual): March 15, 2025

Study Registration Dates

• First Submitted: January 20, 2017
• First Submitted That Met QC Criteria: January 23, 2017
• First Posted (Estimated): January 25, 2017

Study Record Updates

• Last Update Posted (Actual): June 8, 2025
• Last Update Submitted That Met QC Criteria: June 4, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Imprinting Disorders; Neurologic Manifestations; Nervous System Diseases; Pathologic Processes; Nutrition Disorders; Genetic Diseases, Inborn; Overnutrition; Respiratory Tract Diseases; Disease; Neurobehavioral Manifestations; Respiration Disorders; Sleep Wake Disorders; Congenital Abnormalities; Abnormalities, Multiple; Overweight; Apnea; Sleep Disorders, Intrinsic; Dyssomnias; Intellectual Disability; Obesity; Chromosome Disorders; Syndrome; Sleep Apnea Syndromes; Prader-Willi Syndrome; Sleep Apnea, Central
• Other Study ID Numbers: 1000053577

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No