Condition category
Injury, Occupational Diseases, Poisoning
Date applied
16/04/2009
Date assigned
05/08/2009
Last edited
05/02/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr John Simpson

ORCID ID

Contact details

Room C2.12
MRC CIR
Queens Medical Research Centre
Little France Crescent
University of Edinburgh
Edinburgh
EH16 4TJ
United Kingdom
+44 (0)131 242 6556/7
A.J.Simpson@ed.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Trial of monocyte depletion in experimental lung inflammation: a single centre, double-blind, randomised, controlled trial

Acronym

Study hypothesis

In a model of experimental acute lung inflammation in humans, monocyte depletion can ameliorate systemic and pulmonary inflammation.

Ethics approval

Lothian research ethics committee (REC) 1 approved on the 11th May 2009 (ref: 09/S1101/27)

Study design

Single centre double-blind randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Experimental Lung Inflammation

Intervention

Study A:
To characterise the relationship between blood neutrophil/monocyte accumulation and lung inflammation after inhalation of LPS.
Duration of nebulised LPS intervention: 30 - 60 minutes
Duration of Bronchoscopy and BAL: 30 minutes

Study B:
To characterise the effect of mononuclear cell depletion on lung inflammation.
Duration of Leukapheresis: 3 - 6 hours (3 - 4 blood volume changes)
Duration of Bronchoscopy and BAL: 30 minutes

Study C:
Can lung inflammation be reduced by temporarily removing specific white blood cells from the bloodstream? A randomised, double-blind, placebo-controlled trial.
Duration of nebulised LPS intervention: 30 - 60 minutes
Duration of Leukapheresis: 3 - 6 hours (3 - 4 blood volume changes)
Duration of Bronchoscopy and BAL: 30 minutes
Duration of CT-PET: 1 hour

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

Magnitude of LPS-induced neutrophilia after treatment assessed by selective mononuclear leukapheresis, sample taken at 8 hours.

Secondary outcome measures

1. Alveolar pulmonary neutrophil accumulation and injury assessed by bronchoscopy, sample retrieved at 8.5 hours
2. Global pulmonary neutrophil accumulation and injury assessed by positron emission tomography (PET), sample retrieved at 8.5 hours
3. Cytokines in BAL fluid, sample retrieved at 8.5 hours
4. Protein and albumin in BAL fluid, sample retrieved at 8.5 hours
5. Change in oxygen saturation, recordings made every 1 hour (0 - 8 hours, 24 hours and as indicated)
6. Change in serum markers of inflammation, blood drawn 0, 2, 4, 6 and 8 hours (where 0 hours is time just before nebulised LPS)
7. Serial profile of blood neutrophils and monocytes, blood drawn at 0, 2, 4, 6 and 8 hours
8. PET values, scan is at 11 hours
9. Safety and tolerablility, measured throughout

Overall trial start date

01/08/2009

Overall trial end date

31/07/2011

Reason abandoned

Eligibility

Participant inclusion criteria

Healthy male volunteers aged 18 - 40 years

Participant type

Patient

Age group

Adult

Gender

Male

Target number of participants

42 (Study A: 6; Study B: 6; Study C [RCT]: 30)

Participant exclusion criteria

1. Aged less than 18 years
2. History of any chronic or ongoing acute illness (with particular reference to asthma, upper respiratory tract infection, lower respiratory tract infection, bronchiectasis, congenital heart disease, ischaemic heart disease, valvular heart disease, diabetes mellitus, chronic renal impairment, urinary tract infection)
3. Current history of smoking
4. Past smoking history amounting to greater than two pack-years
5. Any history of smoking in the last 12 months
6. Reported alcohol intake greater than 21 units per week
7. Any current medication
8. Abnormal physical signs detected at cardiorespiratory examination
9. Temperature greater than 37.3°C
10. Oxygen saturation less than 95% breathing room air
11. Haemoglobin, white cell count or platelet count outside the laboratory reference range
12. Blood sodium, potassium, urea, creatinine, bilirubin, alanine aminotransferase, random glucose or C-reactive protein outside the laboratory reference range
13. Forced expiratory volume in one second (FEV1) or forced vital capacity (FVC) less than 80% predicted
14. FEV1:FVC ratio less than 70%
15. Any cardiorespiratory abnormality detected on chest x-ray
16. Peripheral venous access insufficient to support bilateral 16 gauge cannulae

Recruitment start date

01/08/2009

Recruitment end date

31/07/2011

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Room C2.12, MRC CIR
Edinburgh
EH16 4TJ
United Kingdom

Sponsor information

Organisation

University of Edinburgh (UK)

Sponsor details

Queen's Medical Research Institute
47 Little France Crescent
Edinburgh
EH16 4TJ
United Kingdom

Sponsor type

University/education

Website

http://www.ed.ac.uk/

Funders

Funder type

Charity

Funder name

Sir Jules Thorn Charitable Trust (UK) (ref: DHR/amh)

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/23627345

Publication citations

  1. Results

    Barr LC, Brittan M, Morris AC, McAuley DF, McCormack C, Fletcher AM, Richardson H, Connell M, Patel D, Wallace WA, Rossi AG, Davidson DJ, Manson L, Turner M, Hirani N, Walsh TS, Anderson NH, Dhaliwal K, Simpson AJ, A randomized controlled trial of peripheral blood mononuclear cell depletion in experimental human lung inflammation., Am. J. Respir. Crit. Care Med., 2013, 188, 4, 449-455, doi: 10.1164/rccm.201212-2334OC.

Additional files

Editorial Notes