London Underground Study - Health Effects of Particulate Matter

• Sponsor: Imperial College London (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04614064
• Collaborator: Medical Research Council (Other)
• Enrollment: 120
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 20.5
• Patients Per Site Per Month: 5.9

Study Details

Study Description

Brief Summary

An average of 4.8 million journeys are made on the London Underground every day and as the 'Tube' has elevated airborne particulate matter concentrations compared to ambient air, this raises concern about the potential health impact of this environment. This study explores the health effects of particulate matter from the London Underground on patients with COPD and healthy volunteers.

Patients with COPD and healthy participants will be invited to undertake a set 90 min journey on the London Underground, and on a separate occasion (3-8 weeks apart), a 90 min journey on the London Overground (as a proxy for a clean air London area while maintaining other aspects of a train journey). A series of clinical, physiological and inflammatory data will be collected before, during and after (at different time points) each of the sessions in order to compare their response in relation to exposure and/or to disease status.

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease	Other: Exposure to London Underground ambient particulate matter; Other: Exposure to London air ambient particulate matter	N/A

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Exposure to Particulate Matter on the London Underground in Healthy Subjects and Patients With Chronic Respiratory Disease
• Actual Study Start Date: Aug 16, 2021
• Anticipated Primary Completion Date: May 1, 2023
• Anticipated Study Completion Date: May 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: COPD patients As per inclusion and exclusion criteria for COPD patients	Other: Exposure to London Underground ambient particulate matter; Exposure to particulate matter on the London Underground; Other: Exposure to London air ambient particulate matter; Exposure to ambient particulate matter on the London Overground (as a proxy as a proxy for a clean air London area while maintaining other aspects of a train journey)
Experimental: Healthy volunteers As per inclusion and exclusion criteria for healthy volunteers	Other: Exposure to London Underground ambient particulate matter; Exposure to particulate matter on the London Underground; Other: Exposure to London air ambient particulate matter; Exposure to ambient particulate matter on the London Overground (as a proxy as a proxy for a clean air London area while maintaining other aspects of a train journey)

Outcome Measures

Primary Outcome Measures

1. The difference (London Underground vs control exposure) in post exposure pulse wave velocity in healthy vs COPD participants. [-2 hours, +2 hours, +5 hours, +6 hours, +24 hours]

   Measurement of arterial stiffness

Secondary Outcome Measures

1. Other clinical responses on the London Underground vs control exposure [-2 hours, 0 hours, +45 minutes +90 minutes, +4 hours, +5 hours, +6 hours, +24 hours]

   Symptom questionnaire

2. Other clinical responses on the London Underground vs control exposure [-2 hours, 0 hours, +45 minutes, +90 minutes, +2 hours, +4 hours, +6 hours, +24 hours]

   Spirometry (FEV1)

3. Other clinical responses on the London Underground vs control exposure [-2 hours, 0 hours, +45 minutes, +90 minutes, +2 hours, +4 hours, +6 hours, +24 hours]

   Spirometry (FVC)

4. Other clinical responses on the London Underground vs control exposure [-2 hours, 0 hours, +45 minutes, +90 minutes, +2 hours, +4 hours, +6 hours, +24 hours]

   Spirometry (FEF 25-75)

5. Other clinical responses on the London Underground vs control exposure [-2 hours, +7 hours, +24 hours]

   Single breath transfer factor for carbon monoxide (TLCO)

6. Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure [-2 hours, +7 hours, +24 hours]

   Blood sample (IL8)

7. Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure [-2 hours, +7 hours, +24 hours]

   Blood sample (High sensitivity CRP)

8. Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure [-2 hours, +7 hours, +24 hours]

   Blood sample (FBC)

9. Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure [-2 hours, +7 hours, +24 hours]

   Blood sample (TNFa)

10. Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure [-2 hours, +7 hours, +24 hours]

    Blood sample (vWf antigen)

11. Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure [-2 hours, +7 hours, +24 hours]

    Blood sample (Thrombin generation (systemic inflammatory response))

12. Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure [-2 hours, +7 hours, +24 hours]

    Blood sample (8-isoprostanes (ELISA))

13. Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure [-2 hours, +7 hours, +24 hours]

    Blood sample (Blood malondialdehyde (lipid peroxidation))

14. Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure [-2 hours, +7 hours, +24 hours]

    Blood sample (Oxidation Reduction Potential (oxidative stress))

15. Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure [-2 hours, +7 hours, +24 hours]

    Nasosorption (IL-8)

16. Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure [-2 hours, +7 hours, +24 hours]

    Nasosorption (IL-6)

17. Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure [-2 hours, +7 hours, +24 hours]

    Nasosorption (IL-33)

18. Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure [-2 hours, +7 hours, +24 hours]

    Nasosorption (Myeloperoxidase)

19. Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure [-2 hours, +7 hours, +24 hours]

    Nasosorption (Neutrophil lipocalin-2)

20. Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure [-2 hours, +7 hours, +24 hours]

    Nasosorption (Tryptases)

21. Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure [-2 hours, +7 hours, +24 hours]

    Nasosorption (Complement)

22. Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure [-2 hours, +7 hours, +24 hours]

    Nasosorption (vWf antigen)

23. Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure [-2 hours, +7 hours, +24 hours]

    Nasosorption (Thrombin generation)

24. Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure [-2 hours, +7 hours, +24 hours]

    Nasosorption (D-dimer activation)

25. Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure [-2 hours, +7 hours, +24 hours]

    Nasal curettage (mRNA levels to elucidate molecular mechanisms that may explain the toxic effects of particulate matter)

26. Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure [-2 hours, +24 hours]

    Urine (8-isoprostane)

27. Circulating inflammatory and oxidative responses after the exposure on the London Underground vs control exposure [-2 hours, +24 hours]

    Urine (8-hydroxy 2-deoxyguanosine)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria for both groups:

• Give informed consent

• London resident

For participants with COPD:

• GOLD stage 2 COPD (FEV1/FVC<70%; 50%>FEV1<80% predicted) and GOLD stage 3 COPD (FEV1/FVC<70%; 30%>FEV1<50).

• No history of ischaemic heart disease

For healthy volunteers:

• No history of ischaemic heart disease.

• Normal lung function with no evidence of airflow obstruction.

Exclusion Criteria for both participants with COPD and healthy volunteers:

• Those with unstable ischaemic heart disease or COPD.

• Current smokers and those who are ex-smokers of <12 months duration.

• Those who work in the London Underground or are occupationally exposed to - - high levels of vehicle traffic exposure on a frequent basis.

• Those who cannot walk for 30 mins.

• Those with hay fever.

• Involvement in another research study

• Those unable to give consent.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Imperial Clinical Research Facility	London		United Kingdom	W12 0HS

Sponsors and Collaborators

• Imperial College London
• Medical Research Council

Investigators

• Principal Investigator: Frank Kelly, Imperial College London

Study Documents (Full-Text)

None provided.

More Information

Publications

• Sinharay R, Gong J, Barratt B, Ohman-Strickland P, Ernst S, Kelly FJ, Zhang JJ, Collins P, Cullinan P, Chung KF. Respiratory and cardiovascular responses to walking down a traffic-polluted road compared with walking in a traffic-free area in participants aged 60 years and older with chronic lung or heart disease and age-matched healthy controls: a randomised, crossover study. Lancet. 2018 Jan 27;391(10118):339-349. doi: 10.1016/S0140-6736(17)32643-0. Epub 2017 Dec 5. Erratum in: Lancet. 2018 Jan 27;391(10118):308.

• Responsible Party: Imperial College London
• ClinicalTrials.gov Identifier: NCT04614064
• Other Study ID Numbers: 20SM6236
• First Posted: Nov 3, 2020
• Last Update Posted: Mar 10, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Imperial College London: COPD; Chronic Obstructive Pulmonary Disease; Particulate matter; London Underground
• Additional relevant MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive

Study Results

No Results Posted as of Mar 10, 2022