The Role of Eicosanoids in the Cardiovascular Actions of Inhaled Nanoparticles

NCT03659864 | Completed

• 2 other identifiers: AC18026SP/15/8/31575
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

Nanoparticles (NPs) are minute pieces of material to which we are exposed every day in the air we breathe. Some are naturally occurring and have no impact on health, whereas others are produced from urban air pollution and can worsen diseases, particularly in the lungs and blood vessels. However, there is great interest in developing new NPs because of their unique properties that are useful for many applications, such as engineering, electronics and for drug delivery. At present it is unclear exactly what effects inhaled NPs have. Our current programme of research is designed to assess whether a specialized group of fats made in the body (called eicosanoids) drive the cardiovascular effects of NPs. The changes in the profiles of these fats will provide unique fingerprints that could be used to predict the actions of new NPs. In the proposed clinical study we shall investigate the effects of both environmental and manufactured carbonaceous NPs on the lungs, blood vessels, blood clotting, and levels of eicosanoids in blood and urine. We have previously investigated the cardiovascular effects of carbon nanoparticles after inhalation in man, and these experiments will investigate how the shape, size and composition of carbon particles influence these responses. These experiments will provide new insight into how NPs affect the body and pave the way for new ways to predict the toxic effects of NPs (reducing the need for animal experiments). The findings will enable the design of novel NP without the harmful characteristics of those found in air pollution.

Conditions

Blood Biomarkers; Vasodilation; Blood Clotting; Lung Function; Healthy Volunteers

Keywords

nanoparticles; pollution

Outcome Measures

Primary Outcomes (2)

• Blood eicosanoid levels

  Eicosanoids in blood (pg/mL)

  Results available within 6 months of final study visit

• Urine eicosanoid levels

  Eicosanoids in urine (pg/mL)

  Results available within 6 months of final study visit

Secondary Outcomes (14)

• blood pressure

  Results available immediately at time of measurement

• Heart rate

  Results available immediately at time of measurement

• Lung function (FEV1)

  Results available immediately at time of measurement

• Lung function (FVC)

  Results available immediately at time of measurement

• Full blood count

  Results available within 3 months of study visit

Study Arms (3)

Exposure 1

SHAM COMPARATOR

filtered air

Other: filtered air

Exposure 2

EXPERIMENTAL

nanoparticle 1 (either DEP or s-GO depending on group)

Other: diesel exhaust particulate; Other: small graphene oxide

Exposure 3

EXPERIMENTAL

nanoparticle 2 (either CB or us-GO depending on group)

Other: carbon nanoparticles; Other: ultrasmall graphene oxide

Interventions

diesel exhaust particulate OTHER

aerosolised diesel exhaust particulate

Also known as: DEP, SRM2975

Exposure 2

carbon nanoparticles OTHER

aerosolised 'clean' carbon nanoparticles

Also known as: carbon black, CB, Printex 90

Exposure 3

small graphene oxide OTHER

aerosolised 'small' graphene oxide

Also known as: s-GO

Exposure 2

ultrasmall graphene oxide OTHER

aerosolised 'ultrasmall' graphene oxide

Also known as: us-GO

Exposure 3

filtered air OTHER

control: filtered air

Also known as: FA

Exposure 1

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Man or woman between 18 to 40 years of age, inclusive
• Judged to be in good health based on medical history, physical examination, vital signs and laboratory tests
• Body mass index (weight kg/m2) between 18 and 35 kg/m2 (inclusive), and body weight between 50 kg and 120 kg (inclusive).
• Willing/able to donate blood (and meets the site's blood donor criteria).
• No severe or significant medical condition and without intercurrent illness (e.g. viral cold or flu, chest infection)
• Not taking any regular oral or intravenous medication.
• Must be willing to abstain from food and caffeine-containing beverages for at least 12 hours beforehand, and alcohol for 24 hours beforehand.

You may not qualify if:

• Smoked tobacco or related products within 1 year prior to the study
• Asthmatic
• Occupation with high exposure to air pollution or other inhaled irritant
• Severe or significant medical condition
• Intercurrent illness (e.g. viral cold or flu, chest infection)
• Use of any regular oral or intravenous prescription medication, or non-prescription (including aspirin, ibuprofen, paracetamol, vitamins and herbal supplements), and not at all in the 7 days prior to the study
• Allergy or contraindication to vasodilator drugs (e.g. acetylcholine or sodium nitroprusside)
• Major or traumatic surgery within 12 weeks of screening
• Pregnant or still lactating prior to dose administration (women only)
• Given blood in the 3 months prior to the study

Sponsors & Collaborators

• University of Edinburgh: lead
• NHS Lothian: collaborator

Study Sites (1)

Centre for Cardiovascular Science

Edinburgh, Midlothian, EH16 4SB, United Kingdom

Location

Related Publications (1)

• Andrews JPM, Joshi SS, Tzolos E, Syed MB, Cuthbert H, Crica LE, Lozano N, Okwelogu E, Raftis JB, Bruce L, Poland CA, Duffin R, Fokkens PHB, Boere AJF, Leseman DLAC, Megson IL, Whitfield PD, Ziegler K, Tammireddy S, Hadjidemetriou M, Bussy C, Cassee FR, Newby DE, Kostarelos K, Miller MR. First-in-human controlled inhalation of thin graphene oxide nanosheets to study acute cardiorespiratory responses. Nat Nanotechnol. 2024 May;19(5):705-714. doi: 10.1038/s41565-023-01572-3. Epub 2024 Feb 16.

  PMID: 38366225 DERIVED

MeSH Terms

Conditions

Aneurysm; Thrombosis

Interventions

1-(2-(dodecyloxy)ethyl)pyrrolidine hydrochloride; Soot

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Embolism and Thrombosis

Intervention Hierarchy (Ancestors)

Smoke; Particulate Matter; Complex Mixtures

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Participant and lead clinical fellow will be blinded. All staff involved in initial data generation will be blinded.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Cohort study with double blind randomised cross over design

Study Record Dates

• First Submitted: August 9, 2018
• First Posted: September 6, 2018
• Study Start: October 3, 2018
• Primary Completion: March 29, 2019
• Study Completion: November 27, 2020
• Last Updated: May 21, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)