Cerebral Palsy, Neurodevelopmental Disorders, Neuromuscular Diseases
Conditions
Keywords
hypertonic saline, saline, nebulised
Brief summary
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.
Interventions
DEVICEsaline
nebulised
Sponsors
Nottingham University Hospitals NHS Trust
Royal Brompton & Harefield NHS Foundation Trust
Pari Pharma GmbH
Imperial College London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Course of antibiotics for respiratory infections | from baseline to week 52 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Forced oscillation technique | at baseline before and within 2 hours after drug response assessment, and at week 52. | Respiratory resistance (Rrs) |
| Lung ultrasound | at baseline before and within 2 hours after drug response assessment, and at week 52. | 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). |
| Electrical Impedance Tomography | at baseline before and within 2 hours after drug response assessment, and at week 52. | 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. |
| Airway inflammation | baseline and at week 52 | Levels of IL-8 in sputum or throat swab. |
| Bacterial diversity | baseline and at week 52 | Operational taxonomic unit (OTU) Richness, defined as count of different species/OTUs. |
| Ease of airway clearance | Once monthly for 52 weeks. | 0-10 Visual analogue scale, where 0 is most easy, and 10 is most difficult. |
| Health-related quality of life | At baseline and at week 51. | Pediatric Quality of Life Inventory (PedsQL)™. 0-100 scale, where higher scores indicate better HRQOL (Health-Related Quality of Life). |
| Patient and main carer treatment satisfaction | weeks 12, 26, 39 and 51 | Treatment Satisfaction Questionnaire for Medication (TSQM Version 1.4). Scores range from 0 to 100, with higher scores indicating higher satisfaction. |
| Family impact | Baseline and at week 51. | 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). |
| Health economics | baseline, week 26 and week 51. | Quality-adjusted life years |
| Lung clearance index | at baseline before and within 2 hours after drug response assessment, and at week 52. | measured by multiple breath washout |
Other
| Measure | Time frame | Description |
|---|---|---|
| Retention rate | 1 year | Percentage of randomised participants retained with valid primary outcome data. |
| Adherence | 52 weeks | Mean percentage of adherence calculated from returned ampoules count |
| Compliance with monthly follow-up | 52 weeks | Percentage of compliance with completion of monthly questionnaires. |
| Success rates of outcome measures | 1 year | Percentage of participants who provided a sputum sample or throat swab |
| Time required to complete outcome measures | 2 hours | Time in minutes to complete acceptable measurements of Lung clearance index |
| Inter-rater reliability of Lung ultrasound analysis | 1 year | 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. |
| Inter-rater reliability of Electrical impedance tomography analysis | 1 year | 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. |
| Consent rate | 1 year | Percentage of eligible participants who consented and were randomised. |
| Recruitment rate | 1 year | Number of participants recruited per centre per month. |
Countries
United Kingdom
Contacts
Primary ContactNatalia G Galaz Souza
Outcome results
None listed