Study of the way unevenness in lung function changes with treatment in airways disease

ISRCTN ISRCTN12223638
DOI https://doi.org/10.1186/ISRCTN12223638
Secondary identifying numbers PID12157
Submission date
11/04/2019
Registration date
10/05/2019
Last edited
02/10/2023
Recruitment status
Recruiting
Overall study status
Completed
Condition category
Respiratory
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Background and study aims
Our research group at the University of Oxford has developed a new type of analyser that very accurately measures the flow of different gases breathed into and out of the lungs. We have also developed a mathematical approach to analysing these data that identifies unevenness (or heterogeneity) of lung function. We believe that these new measurements of heterogeneity may provide important information about lung function that will be useful for the management of patients.

As such, an important aim of the study is to evaluate whether the measures of lung heterogeneity change in response to standard therapy and how they change in comparison to standard clinical markers of airways disease. Another important aim is to determine whether measurements of inhomogeneity can predict response to treatment.

What does the study involve?
In this observational study, we will undertake measurements of lung heterogeneity in up to 100 adult patients with airways diseases at baseline and at various time points along their standard clinical care pathways. The measurements are made during a 15-minute test during which the patient breathes normally through a mouthpiece, with their nose occluded by a nose clip. Each patient will breathe normal air for the first 8-10 min and then 100% oxygen for the final 5 min. These tests will be undertaken at baseline, and before/after therapeutic interventions including inhaled salbutamol, inhaled and/or oral corticosteroids, and/or 'biological' antibody-based therapy. Each patient will be studied for no longer than two years in total.

Who can participate?
Adult patients with airways diseases looked after at Oxford University Hospitals can participate in the study.

What are the possible benefits and risks of participating?
We do not expect participants in this research to benefit directly from their participation, but we hope that the results of the study will benefit patients in the future. We do not expect the gas mixtures breathed during this study to have any adverse health effects, and most patients studied so far have found the tests relatively easy to perform.

Where is the study run from?
The study is running at the University of Oxford and Oxford University Hospitals.

When is the study starting and how long is it expected to run for?
February 2017 to September 2023

Who is funding the study?
The overarching project and the development of the study gas analyser is being funded by the NIHR Oxford Biomedical Research Centre. The particular study of inhomogeneity in lung function before and after therapy is being funded by GlaxoSmithKline UK Limited.

Who is the main contact?
Professor Peter Robbins
peter.robbins@dpag.ox.ac.uk

Contact information

Prof Peter Robbins
Scientific

Department of Physiology, Anatomy & Genetics
Sherrington Building
University of Oxford
Oxford
Oxford
OX1 3PT
United Kingdom

ORCiD logoORCID ID 0000-0002-4975-0609
Phone 01865 272500
Email peter.robbins@dpag.ox.ac.uk

Study information

Study designObservational longitudinal study
Primary study designObservational
Secondary study designLongitudinal study
Study setting(s)Hospital
Study typeOther
Participant information sheet Not available in web format, please use contact details to request a participant information sheet.
Scientific titleHow are non-invasive measures of lung inhomogeneity affected during treatment of airways disease?
Study objectivesWe have developed a method for measuring unevenness of lung function (lung heterogeneity) that provides very sensitive markers of lung physiology. We hypothesise that these markers of lung heterogeneity will change in response to treatment in patients with airways diseases, and may predict therapeutic response.
Ethics approval(s)Approved 17/05/2017, the South Central Oxford A Research Ethics Committee (Bristol Research Ethics Committee Centre, Whitefriars, Level 3 Block B, Lewins Mead, Bristol, BS1 2NT; 0207 1048045; nrescommittee.southcentral-oxforda@nhs.net), ref: 17/SC/0172.
Health condition(s) or problem(s) studiedAirways disease
InterventionCurrent interventions as of 07/12/2022:
This is an observational study in which indices of lung heterogeneity are measured in patients with airways disease. Patients will be studied at baseline and on further occasions over a two-year period, according to their clinical pathway. Measurements will be made before and after clinical interventions (performed as part of clinical care) that might include salbutamol, inhaled or systemic corticosteroids and/or biological therapies.

A “Lung Heterogeneity test” is undertaken which involves breathing on a mouthpiece with the nose occluded for up to 20 minutes. During the test the inspired gas varies from breathing normal air to breathing gas enriched with oxygen (up to 100%), carbon dioxide (up to 8%) and/or trace amounts of acetylene, methane or carbon monoxide (<1%). Up to 4 tests can be performed on a single visit, and these may be performed before and after intervention (e.g. salbutamol inhalation). The composition of inspired and expired gas is analysed continuously using a novel in-airway gas analyser, and collected data are subsequently analysed using a mathematical model of gas exchange.

Participants also undertake additional clinical diagnostic tests of airways function, e.g. spirometry testing, measurement of exhaled nitric oxide (FeNO), induced sputum analysis, blood tests (FBC) and asthma control questionnaire scores (ACQ5).

Participants will be followed up to two years, with multiple visits (as described above) alongside their clinical pathway. All patients give written informed consent.



Previous interventions:
This is an observational study in which indices of lung heterogeneity are measured in patients with airways disease. Patients will be studied at baseline and on further occasions over a two year period, according to their clinical pathway. Measurements will be made before and after clinical interventions (performed as part of clinical care) that might include salbutamol, inhaled or systemic corticosteroids and/or biological therapies.

Participants give written consent for the study. Each study visit coincides with a clinical visit (along the patient’s clinical pathway).

A “Lung Heterogeneity test” is undertaken which involves breathing on a mouthpiece with the nose occluded for up to 20 minutes. During the test the inspired gas varies from breathing normal air to breathing gas enriched with oxygen (up to 100%), carbon dioxide (up to 8%) and/or trace amounts of acetylene, methane or carbon monoxide (<1%). Up to 4 tests can be performed on a single visit, and these may be performed before and after intervention (e.g. salbutamol inhalation). The composition of inspired and expired gas is analysed continuously using a novel in-airway gas analyser, and collected data are subsequently analysed using a mathematical model of gas exchange.

Participants also undertake additional clinical diagnostic tests of airways function, e.g. spirometry testing, measurement of exhaled nitric oxide (FeNO), induced sputum analysis, blood tests (FBC) and asthma control questionnaire scores (ACQ5).

Participants will be followed up to two years, with multiple visits (as described above) along their clinical pathway.
Intervention typeOther
Primary outcome measureChange in lung heterogeneity indices following treatment (pre-treatment baseline, and then 1 week, 5 weeks and/or 3 months post-treatment, depending on the treatment given). The indices are measured during the lung heterogeneity test: σCL:VA (standard deviation of the compliance:volume distribution), σVD:VA (standard deviation of the deadspace:volume distribution) and VDtot/VAtot (ratio of total deadspace to total alveolar volume).
Secondary outcome measures1. Correlation between baseline lung heterogeneity indices and other clinical markers of disease e.g. FeNO, blood eosinophil count, sputum eosinophil count, FEV1, FEV1/FVC ratio and ACQ5 score.
2. Correlation between changes in lung heteroegeneity indices and changes in other clinical markers of disease measured using FeNO, blood eosinophil count, sputum eosinophil count, FEV1, FEV1/FVC ratio and ACQ5 score before and after treatment (1 week, 5 weeks and 3 months).
Overall study start date02/02/2017
Completion date15/09/2023

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants150
Total final enrolment91
Key inclusion criteria1. Aged over 18 years
2. Diagnosis of airways disease
Key exclusion criteria1. Inability to tolerate mouthpiece/nose-clip
2. Pregnancy
Date of first enrolment25/06/2018
Date of final enrolment01/10/2026

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centres

University of Oxford
Department of Physiology, Anatomy & Genetics
Sherrington Building
Parks Road
Oxford
OX1 3PT
United Kingdom
Oxford University Hospitals NHS Foundation Trust
John Radcliffe Hospital
Headington
Oxford
OX3 9DU
United Kingdom

Sponsor information

University of Oxford
University/education

Clinical Trials & Research Governance
Joint Research Office
Boundary Brook House
Headington
Oxford
OX3 7GB
England
United Kingdom

Phone +44 1865 289885
Email ctrg@admin.ox.ac.uk
Website N/A
ROR logo "ROR" https://ror.org/052gg0110

Funders

Funder type

Industry

GlaxoSmithKline
Government organisation / For-profit companies (industry)
Alternative name(s)
GlaxoSmithKline plc., GSK plc., GSK
Location
United Kingdom
NIHR Oxford Biomedical Research Centre

No information available

Results and Publications

Intention to publish date01/03/2024
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot expected to be made available
Publication and dissemination planWe intend to present the results of this study at academic conferences, and to submit reports of the study outcome for peer-reviewed publication in scientific journals.
IPD sharing planCurrent IPD sharing statement as of 07/12/2022:
The datasets generated during and/or analysed during the current study are not expected to be
made available routinely, but requests for data sharing can be made to the study team.


Previous IPD sharing statement:
The data sharing plans for the current study are unknown and will be made available at a later date.

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Interim results article Preliminary results in a small subset of patients and healthy volunteers under same ethics approval 10/03/2020 07/12/2022 Yes No
HRA research summary 28/06/2023 No No
Basic results 30/09/2023 02/10/2023 No No

Additional files

ISRCTN12223638_BasicResults_30Sept2023.pdf

Editorial Notes

02/10/2023: The following changes were made:
1. The overall study end date was changed from 01/04/2027 to 15/09/2023
2. The total final enrolment was added.
3. The recruitment start date was changed from 23/05/2019 to 25/06/2018.
4. The recruitment end date has been changed from 01/10/2026 to 07/10/2022.
5. The intention to publish date was changed from 01/10/2027 to 01/03/2024.
14/12/2022: The following changes were made to the trial record:
1. The recruitment end date has been changed from 01/04/2027 to 01/10/2026.
2. The intention to publish dates has been changed from 01/04/2027 to 01/10/2027.
07/12/2022: The following changes were made to the trial record and the plain English summary was updated accordingly:
1. The overall trial end date has been changed from 01/12/2022 to 01/04/2027.
2. The interventions have been changed.
3. The target number of participants has been changed from 100 to 150.
4. The recruitment end date has been changed from 01/11/2022 to 01/04/2027.
5. The Individual participant data (IPD) sharing statement and summary were changed.
6. The intention to publish date has been changed from 01/04/2023 to 01/04/2027.
7. Publication reference was added.
10/05/2019: Internal review.
08/05/2019: Trial's existence confirmed by the South Central - Oxford A Research Ethics Committee.