Dexamethasone Treatment for OSA in Children

Study Overview
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Brief Summary
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This is a double-blinded clinical trial of children diagnosed with moderate to severe obstructive sleep apnea (OSA) on a baseline polysomnogram (PSG). Participants will receive a 3-day course of dexamethasone, an oral steroid, or placebo control and undergo two PSGs to assess the efficacy of dexamethasone, as a treatment to manage the severity and symptoms in children with moderate to severe OSA.

Detailed Description
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Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder affecting neonates to adolescents characterized by intermittent partial and complete upper airway obstruction leading to apneas. The first line of treatment for OSA in young children is an adenotonsillectomy (AT). However, there are long surgical wait times for ATs, up to 3-6 months after a baseline polysomnogram(PSG). This leaves many children untreated, leading to a higher risk of learning deficits and long-term health effects. Oral corticosteroids have long been used to treat airway inflammation and reduce inflammation of adenoid and tonsil tissue in-vitro. However, there is a lack of knowledge of oral steroids' efficacy in managing OSA. Additionally, the role of the nasal epithelium and the mechanism of action of dexamethasone role at a molecular level is unknown. The primary objective is to evaluate the efficacy of Dexamethasone in reducing the severity and symptoms of moderate to severe OSA in children in this proof-of-concept exploratory trial. Participants will be screened by their baseline PSG, followed by 3 study visits conducted at SickKids. Participants will receive a 3-day course of oral dexamethasone or placebo at their first baseline study visit. During baseline, participants will undergo an otolaryngology assessment, a nasal brushing, and questionnaires. Participants will return 2 to 4 weeks after the intervention to the Hospital for Sick Children for a follow-up study visit which includes a repeat PSG, otolaryngology assessment and questionnaires. If no AT is performed within 6 months, participants will return for a third study visit for a repeat PSG, otolaryngology assessment and questionnaires.

Official Title
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Dexamethasone as a Novel Treatment for Obstructive Sleep Apnea in Children

Conditions
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Obstructive Sleep Apnea

Intervention / Treatment
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* Drug: Dexamethasone
* Drug: Placebo Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Polysomnogram diagnosed with moderate to severe Obstructive sleep apnea (OAHI >5 events/hour) Aged 2-10 years Presence of adenotonsillar hypertrophy Ability to take oral medication and be willing to adhere to the dosing regimen Informed consent provided in accordance with institutional policies Exclusion Criteria: Previous adenotonsillectomy Presence of symptoms of an upper respiratory tract infection Co-existing central sleep apnea Hypertension Prior or current evidence for abnormal glucose tolerance Contraindication for dexamethasone or components of dexamethasone oral suspension, Treatment with nasal or systemic corticosteroids within 4 weeks prior to the intervention OSA with associated oxygen desaturations <90% for 2 continuous minutes Need for non-invasive ventilation long-term due to underlying disease Current systemic fungal infections Patients with clinically relevant varicella exposure

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 10 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: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dexamethasone Treatment<br>Oral Dexamethasone treatment | Drug: Dexamethasone<br>* Dexamethasone Oral Suspension<br>|
| Placebo Comparator: Placebo Treatment<br>Placebo control | Drug: Placebo Control<br>* Placebo Oral Mix<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Obstructive apnea-hypopnea index | Change in obstructive apnea-hypopnea index from baseline. The paediatric OSA severity scoring criteria will be used for all participants. Mild OSA is defined as OAHI ≥1 to <5 events/hr; moderate OSA is defined as OAHI ≥5 to <10 events/hr; and severe OSA is defined as OAHI ≥10 events/hr | Baseline and 2-4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in scores from baseline of the Child Sleep Habits Questionnaire (CSHQ) total score | Total CSHQ score of 41 has been reported to be a sensitive clinical cut-off point for detecting possible sleep problems | Baseline and 2-4 weeks | 
| Change in scores from baseline of the Strengths and Difficulties Questionnaire (SDQ) | The SDQ is a validated parent-reported behavioural screening questionnaire and is used to assess children's mental health. The total difficulties score ranges from 0 to 40, a higher score indicates higher difficulties. | Baseline and 2-4 weeks | 
| Change in scores from baseline of the Obstructive Sleep Apnea-18 Quality of Life (OSA-18 QoL) Survey. | The OSA-18 QoL survey is a validated 18-item quality of life measure for children with sleep-disordered breathing (SDB) for children 2-18. Higher total scores indicate more impact on QoL - minor impact (scores below 60), moderate impact (scores between 60 and 80) and major impact (scores above 80). | Baseline and 2-4 weeks | 
| Soft tissue size (Adenoids, Tonsils & Turbinates) | Change in soft tissue size (adenoids, tonsils and turbinates) from baseline | Baseline and 2-4 weeks | 
| Cytokine levels of Interleukin-8(IL-8), Interleukin-1b(IL1b), and Tumor Necrosis Factor a (TNFa) at baseline | Inflammatory markers will be measured in basal media of cells cultured from nasal brushing by ELISA | At baseline | 
| Inflammatory gene expression of Interleukin-8, Interleukin-1b, Nuclear factor kappa-B (NF-kB) and Tumor Necrosis Factor a (TNFa) | Cells from nasal brushing will be cultured and harvested for RNA to study gene expression. | At baseline | 
| Participant recruitment rate | Feasibility determined by participant recruitment rate | From study start to completion; up to 6 months | 
| Participant retention rate | Feasibility determined by participant retention rate | From study start to completion; up to 6 months | 
| Participant adherence rate | Feasibility determined by participant adherence rate | From study start to completion; up to 6 months | 
| Adverse events | Safety determined by number and severity of adverse events | From study start to completion; up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dexamethasone, Corticosteroid