Condition category
Respiratory
Date applied
11/04/2019
Date assigned
10/05/2019
Last edited
10/05/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

Plain English Summary

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?
The study is starting in March 2019 and is expected to run for 2 years, until the required number of participants are recruited.

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

Trial website

Contact information

Type

Scientific

Primary contact

Prof Peter Robbins

ORCID ID

http://orcid.org/0000-0002-4975-0609

Contact details

Department of Physiology
Anatomy & Genetics
Sherrington Building
University of Oxford
Oxford
Oxford
OX1 3PT
United Kingdom
01865 272500
peter.robbins@dpag.ox.ac.uk

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

PID12157

Study information

Scientific title

How are non-invasive measures of lung inhomogeneity affected during treatment of airways disease?

Acronym

Study hypothesis

We 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

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.

Study design

Observational longitudinal study

Primary study design

Observational

Secondary study design

Longitudinal study

Trial setting

Hospitals

Trial type

Other

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet.

Condition

Airways disease.

Intervention

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 type

Other

Phase

Drug names

Primary outcome measure

Change 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 measures

1. 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 trial start date

02/02/2017

Overall trial end date

01/12/2022

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Aged over 18 years
2. Diagnosis of airways disease

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

100

Participant exclusion criteria

1. Inability to tolerate mouthpiece/nose-clip
2. Pregnancy

Recruitment start date

23/05/2019

Recruitment end date

01/11/2022

Locations

Countries of recruitment

United Kingdom

Trial participating centre

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

Trial participating centre

Oxford University Hospitals NHS Foundation Trust
John Radcliffe Hospital Headington
Oxford
OX3 9DU
United Kingdom

Sponsor information

Organisation

University of Oxford

Sponsor details

Clinical Trials & Research Governance
Joint Research Office
Boundary Brook House
Headington
Oxford
OX3 7GB
United Kingdom
+44 1865 289885
ctrg@admin.ox.ac.uk

Sponsor type

University/education

Website

N/A

Funders

Funder type

Industry

Funder name

GlaxoSmithKline

Alternative name(s)

GlaxoSmithKline plc., GSK

Funding Body Type

private sector organisation

Funding Body Subtype

For-profit companies (industry)

Location

United Kingdom

Funder name

NIHR Oxford Biomedical Research Centre

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

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

Intention to publish date

01/04/2023

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

10/05/2019: Internal review. 08/05/2019: Trial's existence confirmed by the South Central - Oxford A Research Ethics Committee.