Clinical trial NCT03031626: Oxygen Versus Medical Air for Treatment of CSA in Prader Will Syndrome
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Sleep Apnea, Central
Prader-Willi Syndrome
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
First posted: 2017-01-25
Enrollment: 9
Sex: ALL
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Delta CAHI1
timeFrame: 2 years
measure: Delta CAHI2
timeFrame: 2 years
measure: Difference in CAHI1 and CAHI2
timeFrame: 2 years
Secondary outcomes:
measure: Arousal Index1
timeFrame: 2 years
measure: Arousal Index2
timeFrame: 2 years
measure: Desaturation Index1
timeFrame: 2 years
measure: Desaturation Index2
timeFrame: 2 years
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: The Hospital for Sick Children
name: Reshma Amin, MD
role: PRINCIPAL_INVESTIGATOR
References: