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

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

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.

Study Overview

• Status: Completed
• Conditions: Neuromuscular Diseases
• Intervention / Treatment: Drug: Nebulised hypertonic saline

Detailed Description

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:

1. The National Health and Nutrition Examination Survey (NHANES) for Hospitalisation and access to are - HUQ.010; and
2. Questionnaire on Hypertonic Saline treatment.

Children from 10 - 18 years will be asked to complete the Questionnaire on Hypertonic Saline treatment.

AIMS

1. Explore whether treatment with nebulised Hypertonic Saline in children with Neuromuscular disease or Cerebral Palsy decreases respiratory-related complications.
2. Evaluate whether the treatment with nebulised hypertonic saline in children with neuromuscular disease or cerebral palsy improves the ease of airway clearance.
3. 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.

• Study Type: Observational
• Enrollment (Actual): 24

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SW36NP
    • Royal Brompton Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 18 years (Child, Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Children with Neuromuscular disease or Cerebral Palsy who have their care at the Royal Brompton Hospital.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Before treatment; Children and young people with neuromuscular disease during the 12 months before being prescribed treatment with nebulised saline (0.9% - 7%)
After treatment; 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; Nebulised hypertonic saline used for a period of at least 12 months; Other Names: 3% Sodium Chloride; 5% Sodium Chloride; 7% Sodium Chloride

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: Royal Brompton & Harefield NHS Foundation Trust
• Investigators: Principal Investigator: Natalia Galaz Souza, Professional, Imperial College London

Publications and helpful links

General Publications

• Elkins MR, Robinson M, Rose BR, Harbour C, Moriarty CP, Marks GB, Belousova EG, Xuan W, Bye PT; National Hypertonic Saline in Cystic Fibrosis (NHSCF) Study Group. A controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis. N Engl J Med. 2006 Jan 19;354(3):229-40. doi: 10.1056/NEJMoa043900.
• Phillips MF, Quinlivan RC, Edwards RH, Calverley PM. Changes in spirometry over time as a prognostic marker in patients with Duchenne muscular dystrophy. Am J Respir Crit Care Med. 2001 Dec 15;164(12):2191-4. doi: 10.1164/ajrccm.164.12.2103052.
• Amin R, Subbarao P, Jabar A, Balkovec S, Jensen R, Kerrigan S, Gustafsson P, Ratjen F. Hypertonic saline improves the LCI in paediatric patients with CF with normal lung function. Thorax. 2010 May;65(5):379-83. doi: 10.1136/thx.2009.125831.
• Boitano LJ. Management of airway clearance in neuromuscular disease. Respir Care. 2006 Aug;51(8):913-22; discussion 922-4.
• Allen J. Pulmonary complications of neuromuscular disease: a respiratory mechanics perspective. Paediatr Respir Rev. 2010 Mar;11(1):18-23. doi: 10.1016/j.prrv.2009.10.002. Epub 2009 Dec 2.
• Lo Mauro A, Aliverti A. Physiology of respiratory disturbances in muscular dystrophies. Breathe (Sheff). 2016 Dec;12(4):318-327. doi: 10.1183/20734735.012716.
• Gerdung CA, Tsang A, Yasseen AS 3rd, Armstrong K, McMillan HJ, Kovesi T. Association Between Chronic Aspiration and Chronic Airway Infection with Pseudomonas aeruginosa and Other Gram-Negative Bacteria in Children with Cerebral Palsy. Lung. 2016 Apr;194(2):307-14. doi: 10.1007/s00408-016-9856-5. Epub 2016 Feb 16.
• Bell CF, Kurosky SK, Candrilli SD. Muscular dystrophy-related hospitalizations among male pediatric patients in the United States. Hosp Pract (1995). 2015;43(3):180-5. doi: 10.1080/21548331.2015.1033375. Epub 2015 Apr 1.
• Yuan JX, McGowan M, Hadjikoumi I, Pant B. Do children with neurological disabilities use more inpatient resources: an observational study. Emerg Themes Epidemiol. 2017 Apr 27;14:5. doi: 10.1186/s12982-017-0059-1. eCollection 2017.
• Elkins MR, Bye PT. Mechanisms and applications of hypertonic saline. J R Soc Med. 2011 Jul;104 Suppl 1(Suppl 1):S2-5. doi: 10.1258/jrsm.2011.s11101. No abstract available.
• Galaz Souza N, Bush A, Tan HL. Exploratory study of the effectiveness of nebulised saline in children with neurodisability. Eur Respir J. 2021 Mar 18;57(3):2001407. doi: 10.1183/13993003.01407-2020. Print 2021 Mar.

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2018
• Primary Completion (Actual): August 14, 2019
• Study Completion (Actual): September 26, 2019

Study Registration Dates

• First Submitted: July 16, 2018
• First Submitted That Met QC Criteria: August 8, 2018
• First Posted (Actual): August 9, 2018

Study Record Updates

• Last Update Posted (Actual): September 16, 2020
• Last Update Submitted That Met QC Criteria: August 26, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: children; adolescents; young people; Hypertonic saline; respiratory; nebulised
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Damage, Chronic; Cerebral Palsy; Neuromuscular Diseases
• Other Study ID Numbers: 18IC4403

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Data ownership rights will lie with the institution.

Drug and device information, study documents

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