Nebulised Hypertonic Saline to Decrease Respiratory Exacerbations in Neuromuscular Disease or Neurodisability (SPICE-UP)

Effectiveness of Nebulised Hypertonic Saline to Decrease Respiratory Exacerbations in People With Neuromuscular Disease or Neurodisability: a Phase 2 Open Label Pilot Study

Research Aim: This study investigates whether a 12-month treatment with hypertonic saline (salty water) can reduce antibiotic use in individuals with neuromuscular disease or cerebral palsy who frequently experience chest infections due to difficulty clearing mucus from their airways.

Methodology: Participants will be randomly assigned to receive nebulised hypertonic saline (7% salt in water) or normal saline (0.9% salt in water). The study is open-label as both participants and researchers are aware of the treatment, necessary due to the differing tastes of the solutions. Two centers, Royal Brompton Hospital in London and Queens Medical Centre in Nottingham, will conduct the research.

Before starting the treatment, participants will undergo various assessments, including questionnaires to measure quality of life and treatment satisfaction, sputum/throat swab collection, lung clearance index, forced oscillation technique, electrical impedance tomography, and lung ultrasound. Once these assessments are completed, participants will take the assigned treatment at home, administered twice daily for 12 months, with monthly follow-ups regarding difficulties and chest infections. After 12 months, the treatment will cease, and participants will repeat the assessments.

Significance: This research will provide valuable insights into the efficacy of nebulised hypertonic saline for individuals with neuromuscular disease or cerebral palsy, potentially aiding both patients and doctors in making informed treatment decisions.

Dissemination: The study's findings will be shared through publication in scientific journals and presentation at conferences.

Study Overview

• Status: Not yet recruiting
• Conditions: Cerebral Palsy; Neuromuscular Diseases; Neurodevelopmental Disorders
• Intervention / Treatment: Device: saline

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Natalia G Galaz Souza; Phone Number: 0787131892; Email: natalia.galaz-souza16@imperial.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom, SW3 6NP
    • Royal Brompton Hospital
    • Contact: Natalia Galaz Souza; Phone Number: +447871331892; Email: natalia.galaz-souza16@imperial.ac.uk
    • Contact: Email: natalia.galaz-souza16@imperial.ac.uk
    • Principal Investigator: Natalia Galaz Souza
    • Sub-Investigator: Andrew Bush, Professor
    • Sub-Investigator: Hui-Leng Tan, Dr
    • Sub-Investigator: Mathew Hurley, Dr
  • Nottingham, United Kingdom, NG7 2UH
    • Nottingham University Hospitals
    • Principal Investigator: Natalia Galaz Souza
    • Sub-Investigator: Andrew Bush, Professor
    • Sub-Investigator: Hui-Leng Tan, Dr
    • Sub-Investigator: Mathew Hurley, Dr
    • Contact: Natalia G Souza; Phone Number: 07871331892; Email: natalia.galaz-souza16@imperial.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of NMD or neurodisablity by a physician independent of the study, on standard criteria.
• Age 5 years and above, including adults.
• Must be able to tolerate nebulised 6% hypertonic saline.
• Must have a history of at least one respiratory exacerbation requiring antibiotic treatment with or without the need for hospitalisation in the 12 months prior to recruitment.

Exclusion Criteria:

• Patients with additional diagnosis, for example, CF, but those with aspiration and/or bronchiectasis secondary to respiratory complications of NMD will be included.
• Patients who are already prescribed daily HS in any concentration (i.e, 3%, 5%, 6%, 7%) will be excluded, but those who are on daily NS or have HS prescribed as part of their escalation plan (i.e., PRN) will be included.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Nebulised 6% Hypertonic saline	Device: saline; nebulised
Placebo Comparator: Control; Nebulised 0.9% normal saline	Device: saline; nebulised

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Course of antibiotics for respiratory infections	Full courses of antibiotics as prescribed for respiratory infections, both oral and intravenous, (excluding prophylactic antibiotic prescriptions). 1 course of antibiotic would be the full treatment for one event of respiratory infection, irrespective of the number of days that the course was prescribed for.	from baseline to week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lung clearance index	measured by multiple breath washout	at baseline before and within 2 hours after drug response assessment, and at week 52.
Forced oscillation technique	Respiratory resistance (Rrs)	at baseline before and within 2 hours after drug response assessment, and at week 52.
Forced oscillation technique	Respiratory reactance (Xrs).	at baseline before and within 2 hours after drug response assessment, and at week 52.
Lung ultrasound	Global Lung ultrasound score. The global lung ultrasound score (LUS) quantifies lung aeration by translating lung ultrasound patterns into a numerical score across 12 lung regions (six areas on each side of the chest: two ventral regions, two lateral regions, and two posterolateral regions) and summing the results. The aeration pattern observed in each region is scored from 0 to 3 as follows: 0 = A pattern with ≤2 B lines; 1 = >2 separated B lines that cover ≤50% of the pleural line; 2 = B lines that cover >50% of the pleural line; or 3 = lung consolidation. In theory, the global LUS score can range from 0 (normal aeration in all regions) to 36 (severe abnormal aeration in all regions).	at baseline before and within 2 hours after drug response assessment, and at week 52.
Electrical Impedance Tomography	Electrical impedance tomography (EIT)-based global inhomogeneity index (quantification of homogeneity of the tidal volume distribution). The image matrix in EIT consists of 32 × 32 pixels. Global inhomogeneity (GI) is calculated as the sum of the absolute differences between the median value of tidal variation and every single pixel value, divided by the sum of all impedance values, to normalise the calculated values.The smaller the GI, the more homogeneous the tidal volume is distributed within the ventilated area. A GI of zero represents a perfectly homogeneous distribution of ventilation.	at baseline before and within 2 hours after drug response assessment, and at week 52.
Airway inflammation	Levels of IL-8 in sputum or throat swab.	baseline and at week 52
Airway inflammation	Levels of IL-6 in sputum or throat swab.	baseline and at week 52
Airway inflammation	Levels of TNF-a in sputum or throat swab.	baseline and at week 52
Airway inflammation	Levels of IL-1b in sputum or throat swab.	baseline and at week 52
Bacterial diversity	Operational taxonomic unit (OTU) Richness, defined as count of different species/OTUs.	baseline and at week 52
Bacterial diversity	Pielou's eveness index. Pielou's evenness is an index that measures diversity along with species richness.	baseline and at week 52
Bacterial diversity	Shannon diversity index. The index takes into account the number of species living in a habitat (richness) and their relative abundance (evenness).	baseline and at week 52
Bacterial diversity	Bray-Curtis dissimilarity index. Examines the abundances of microbes that are shared between two samples, and the number of microbes found in each.	baseline and at week 52
Ease of airway clearance	0-10 Visual analogue scale, where 0 is most easy, and 10 is most difficult.	Once monthly for 52 weeks.
Health-related quality of life	Pediatric Quality of Life Inventory (PedsQL)™. 0-100 scale, where higher scores indicate better HRQOL (Health-Related Quality of Life).	At baseline and at week 51.
Patient and main carer treatment satisfaction	Treatment Satisfaction Questionnaire for Medication (TSQM Version 1.4). Scores range from 0 to 100, with higher scores indicating higher satisfaction.	weeks 12, 26, 39 and 51
Family impact	PedsQL™ Family Impact Module. The scale has five Likert response options, 'never', 'almost never', 'sometimes', 'often' and 'almost always' (corresponding to scores of 100, 75, 50, 25 and 0). Regarding the interpretation of the scale, higher scores indicate better functioning (less negative impact).	Baseline and at week 51.
Health economics	Quality-adjusted life years	baseline, week 26 and week 51.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment rate	Number of participants recruited per centre per month.	1 year
Consent rate	Percentage of eligible participants who consented and were randomised.	1 year
Retention rate	Percentage of randomised participants retained with valid primary outcome data.	1 year
Adherence	Mean percentage of adherence calculated from returned ampoules count	52 weeks
Adherence	Pick-up rate as the percentage of picked up prescriptions from total prescribed doses	52 weeks
Adherence	The Medication Adherence Report Scale (MARS) Score, where each of the 5 items are summed to give a scale score ranging from 5 to 25, where higher scores indicate higher levels of reported adherence.	52 weeks
Compliance with monthly follow-up	Percentage of compliance with completion of monthly questionnaires.	52 weeks
Success rates of outcome measures	Percentage of participants who provided a sputum sample or throat swab	1 year
Success rates of outcome measures	Percentage of participants who completed acceptable measurements of Lung clearance index	1 year
Success rates of outcome measures	Percentage of participants who completed acceptable measurements of Forced oscillation technique	1 year
Success rates of outcome measures	Percentage of participants who completed acceptable measurements of Lung ulstrasound	1 year
Success rates of outcome measures	Percentage of participants who completed acceptable measurements of Electrical impedance tomography	1 year
Time required to complete outcome measures	Time in minutes to complete acceptable measurements of Lung clearance index	2 hours
Time required to complete outcome measures	Time in minutes to complete acceptable measurements of forced oscillation technique	2 hours
Inter-rater reliability of Lung ultrasound analysis	Degree of agreement among independent observers using Cohen Kappa. Cohen suggested the Kappa result be interpreted as follows: values ≤ 0 as indicating no agreement and 0.01-0.20 as none to slight, 0.21-0.40 as fair, 0.41- 0.60 as moderate, 0.61-0.80 as substantial, and 0.81-1.00 as almost perfect agreement.	1 year
Inter-rater reliability of Electrical impedance tomography analysis	Degree of agreement among independent observers using Cohen Kappa. Cohen suggested the Kappa result be interpreted as follows: values ≤ 0 as indicating no agreement and 0.01-0.20 as none to slight, 0.21-0.40 as fair, 0.41- 0.60 as moderate, 0.61-0.80 as substantial, and 0.81-1.00 as almost perfect agreement.	1 year

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: Nottingham University Hospitals NHS Trust; Royal Brompton & Harefield NHS Foundation Trust; Pari Pharma GmbH
• Investigators: Principal Investigator: Andrew Bush, Professor, Imperial College London

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: November 3, 2023
• First Submitted That Met QC Criteria: November 10, 2023
• First Posted (Actual): November 18, 2023

Study Record Updates

• Last Update Posted (Actual): October 15, 2024
• Last Update Submitted That Met QC Criteria: October 14, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: hypertonic saline; saline; nebulised
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Damage, Chronic; Cerebral Palsy; Neurodevelopmental Disorders; Neuromuscular Diseases
• Other Study ID Numbers: 23IC8597

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data ownership rights will lie with the institution
• IPD Sharing Time Frame: Data will become available after all study activities have finished. It will be available for 10 years.
• IPD Sharing Access Criteria: Data ownership rights will lie with the institution
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No