Nebulised Hypertonic Saline in Children and Young People With Neuromuscular Disease and Cerebral Palsy

Study Overview
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Brief Summary
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Pneumonia, respiratory exacerbations, and chronic pulmonary infection are important causes of emergency admissions, hospitalisations and death in children with Neuromuscular disorders and Cerebral Palsy. Hence, there is a need for research on how to therapeutically aid airway clearance and decrease respiratory exacerbations. Studies have shown that nebulised Hypertonic Saline is well tolerated, reduces pulmonary exacerbations and improves lung function and Lung Clearance Index in patients with Cystic Fibrosis, and enhances mucociliary clearance in asthmatic patients. Nevertheless, to the investigators' knowledge, there is no available data concerning the use of nebulised Hypertonic Saline in the management of children with Neuromuscular disorders and Cerebral Palsy. This study aims to assess the effectiveness of nebulised Hypertonic Saline to decrease hospitalisations and courses of antibiotics in children with Neuromuscular disorders and Cerebral Palsy.

Detailed Description
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Chart review of children and young people with Neuromuscular disease or Cerebral Palsy who are cared for in the Royal Brompton Hospital and that have been treated with nebulised hypertonic saline for at least 12 months. To further complement data from hospital records, two questionnaires will be applied. Parents of children who meet criteria will be asked to complete the following questionnaires: The National Health and Nutrition Examination Survey (NHANES) for Hospitalisation and access to are - HUQ.010; and Questionnaire on Hypertonic Saline treatment. Children from 10 - 18 years will be asked to complete the Questionnaire on Hypertonic Saline treatment. AIMS Explore whether treatment with nebulised Hypertonic Saline in children with Neuromuscular disease or Cerebral Palsy decreases respiratory-related complications. Evaluate whether the treatment with nebulised hypertonic saline in children with neuromuscular disease or cerebral palsy improves the ease of airway clearance. Explore how parents of children with Neuromuscular disease and children with Cerebral Palsy perceive the treatment with nebulised hypertonic saline compared with previous management. Sample Size: The investigators aim to recruit 40 participants for each group, including children and young people and their parents or legal guardians, as this is a pilot study. STATISTICAL ANALYSIS PLAN Univariate X2 analysis for categorical variables to investigate Courses of antibiotic treatment. Univariate X2 analysis for categorical variables to investigate Number of hospitalisations. Student t testing will be used to analyse nocturnal oxygenation and ventilation outcomes comparing one year before and after starting treatment with Hypertonic Saline. Independent t testing and Mann-Whitney U test to analyse Rate of decline in pulmonary function. Cox proportional hazard model to test differences in primary endpoints for different baseline FVC. Univarate analysis to analyse Ease of airway clearance. Univariate analysis on perception of treatment. Data and all appropriate documentation will be stored for a minimum of 10 years after the completion of the study, including the follow-up period. ETHICS APPROVAL The Study Coordination Centre has obtained approval from the Yorkshire & The Humber - Leeds West Research Ethics Committee (REC) and Health Regulatory Authority (HRA). The study also received confirmation of capacity and capability from each participating NHS Trust before accepting participants into the study or any research activity was carried out. The study will be conducted in accordance with the recommendations for physicians involved in research on human subjects adopted by the 18th World Medical Assembly, Helsinki 1964 and later revisions. CONSENT Consent to enter the study must be sought from each participant only after a full explanation has been given, an information leaflet offered and time allowed for consideration. Signed participant consent should be obtained. The right of the participant to refuse to participate without giving reasons must be respected. After the participant has entered the study the clinician remains free to give alternative treatment to that specified in the protocol at any stage if he/she feels it is in the participant's best interest, but the reasons for doing so should be recorded. In these cases the participants remain within the study for the purposes of follow-up and data analysis. All participants are free to withdraw at any time from the protocol treatment without giving reasons and without prejudicing further treatment. CONFIDENTIALITY The Chief Investigator will preserve the confidentiality of participants taking part in the study and is registered under the Data Protection Act. PUBLICATION POLICY Data ownership rights will lie with the institution. Findings of this study will be presented as a Dissertation and will be available through Open Access. The investigators aim to publish findings in peer-review journals.

Official Title
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A Chart Review Assessing the Effects of Nebulised Hypertonic Saline on Respiratory-related Complications in Children and Young People With Neuromuscular Disease and Cerebral Palsy

Conditions
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Neuromuscular Diseases

Intervention / Treatment
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* Drug: Nebulised hypertonic saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children with Neuromuscular disease or Cerebral Palsy who have been on treatment with nebulised Hypertonic Saline for at least 12 months. Exclusion Criteria: Children also diagnosed with cystic fibrosis.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Before treatment<br>Children and young people with neuromuscular disease during the 12 months before being prescribed treatment with nebulised saline (0.9% - 7%) | |
| After treatment<br>Children and young people with neuromuscular disease during the 12 months after being prescribed treatment with nebulised saline (0.9% - 7%) | Drug: Nebulised hypertonic saline<br>* Nebulised hypertonic saline used for a period of at least 12 months<br>* Other names: 7% Sodium Chloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Antibiotic Courses | Treatments due to respiratory exacerbations | Change from baseline (before treatment) and 12 months after treatment | 
| Number of Hospitalsations Due to Respiratory Exacerbations | Number of respiratory exacerbations that required not planned hospitalisation | Change from baseline (before treatment) and 12 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participant's Perception of Treatment | Questionnaire: Hypertonic saline treatment questionnaire. Perception of overall usefulness of nebulised hypertonic saline: Useful, Not useful, I don't know. | At 12 months after starting treatment with hypertonic saline | 
| Parent's or Legal Guardian's Perception of Treatment | Hypertonic saline treatment questionnaire for legal guardian. Measures the perception of overall usefulness of nebulised hypertonic saline through a likert scale: Very useful, useful, neither useful or not useful, not useful, not at all useful. | At 12 months after starting treatment with hypertonic saline | 
| Score on the Ease of Airway Clearance Pictorial Analogue Scale From Children and Young Adults as Participants | Pictorial visual scale Facial Rating of perceived exertion Scale. Measures ease of airway clearance. Values range starting in 0 (Extremely easy) to 10 (Extremely hard), including 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10. Numbers are also associated with facial expressions. | Change from baseline (before treatment) and 12 months after treatment | 
| Score on the Ease of Airway Clearance From Parents or Legal Guardians | Measures ease of airway clearance through a 1-5 likert scale: 1) Very easy, 2) Easy, 3) Neither easy nor difficult, 4) Not easy, 5) Not at all easy. | Change from baseline (before treatment) and 12 months after treatment | 
| Apnea Index (AI) | The number of apneas recorded during the study per hour of sleep | Change from baseline (before treatment) and 12 months after treatment | 
| AHI | Nocturnal Apnoea Hipopnea index: total number of apnea events plus hypopnea events divided by the total number of minutes of actual sleep time and then multiplied by 60. | Change from baseline (before treatment) and 12 months after treatment | 
| %SpO2 | Nocturnal oxygen saturation | Change from baseline (before treatment) and 12 months after treatment | 
| Nocturnal ODI | Oxygen desaturation index: Number of desaturations per hour of sleep | Change from baseline (before treatment) and 12 months after treatment | 
| TcPCO2 | Nocturnal Transcutaneous Carbon Dioxide in kPa | Change from baseline (before treatment) and 12 months after treatment | 
| FEV1/FVC %Predicted Rate of Decline | Rate of decline per year of Tiffenau index | Change from baseline (before treatment) and 12 months after treatment | 
| FEV1% Predicted Rate of Decline | Rate of decline of Forced Expiratory Volume in first second (FEV1) percentage of predicted. Rate of decline is a measure of slope of FEV1 percentage predicted. Baseline slope: [(FEV1% at baseline / FEV1% 12 months before treatment) - 1] * 100 After treatment slope: [(FEV1% 12 months after treatment / FEV1% at baseline) - 1] * 100 | Change from the baseline (before treatment) and 12 months after treatment | 
| FVC% Predicted Rate of Decline | Rate of decline of Forced Vital Capacity (FVC) percentage of predicted. Rate of decline is a measure of slope of FVC%. Baseline slope: [(FVC% at baseline / FVC% 12 months before treatment) - 1] * 100 After treatment slope: [(FVC% 12 months after treatment / FVC% at baseline) - 1] * 100 | Change from baseline (before treatment) and 12 months after treatment | 
| Peak Expiratory Flow (PEF) | Peak expiratory flow percentage of predicted | Change from baseline peak expiratory flow at 12 months after starting treatment with hypertonic saline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertonic saline, nebulised, children, young people, adolescents, respiratory