NCT00845767

Brief Summary

Exposure to air pollution has been linked to increased cardiorespiratory morbidity and mortality. The exact component of air pollution that mediates this effect is unknown, but the link is strongest for fine combustion derived particulate matter derived from traffic sources. Recently, it has been demonstrated that inhalation of diesel exhaust impairs vascular vasomotor tone and endogenous fibrinolysis. The mechanism underlying these detrimental vascular is unclear, but is thought to be via oxidative stress and altered bioavailability of endogenous nitric oxide. In these studies we plan to elucidate the role of endogenous nitric oxide (NO) in the adverse vascular responses observed following exposure to diesel exhaust.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
16

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Apr 2009

Shorter than P25 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 17, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

February 18, 2009

Completed
1 month until next milestone

Study Start

First participant enrolled

April 1, 2009

Completed
3 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2009

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2009

Completed
Last Updated

October 9, 2009

Status Verified

October 1, 2009

Enrollment Period

3 months

First QC Date

February 17, 2009

Last Update Submit

October 8, 2009

Conditions

Endothelial Dysfunction

Keywords

Nitric OxideNitric Oxide SynthaseAir PollutionEndothelial DysfunctionDiesel Exhaust

Outcome Measures

Primary Outcomes (1)

  • Forearm blood flow as measured by venous occlusion plethysmography during infusion of NOS inhibitors and vasodilators

    2-4 hours after exposure

Secondary Outcomes (2)

  • Plasma nitrite concentrations

    During forearm study

  • Plasma concentrations of t-PA and PAI

    After infusion of bradykinin during forearm study

Study Arms (2)

Diesel Exposure

EXPERIMENTAL

1 hour exposure to dilute diesel exhaust at a concentration of 300 µg/m3 with intermittent exercise

Procedure: Forearm Vascular Study

Air Exposure

EXPERIMENTAL

1 hour exposure to filtered air during intermittent exercise

Procedure: Forearm Vascular Study

Interventions

Forearm Vascular StudyPROCEDURE

Forearm venous occlusion plethysmography during intraarterial infusion of L-NMMA (2-8 µmol/min) followed by co-infusion of sodium nitroprusside (90-900 ng/min) as a "nitric oxide clamp". Forearm blood flow then measured during the clamp in response to infused vasodilators acetylcholine (5-20 mg/min), bradykinin (100-1000 pmol/min), verapamil (10-100 µg/min) and sodium nitroprusside (2-8 µg/min).

Also known as: ACh, SNP, BK
Air ExposureDiesel Exposure

Eligibility Criteria

Age18 Years - 40 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Healthy volunteers

You may not qualify if:

  • Use of regular medication (except oral contraceptive pill)
  • Current smokers
  • Significant occupational exposure to air pollution
  • Intercurrent illness

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Umeå University

Umeå, Sweden

Location

Related Publications (2)

  • Mills NL, Tornqvist H, Robinson SD, Gonzalez M, Darnley K, MacNee W, Boon NA, Donaldson K, Blomberg A, Sandstrom T, Newby DE. Diesel exhaust inhalation causes vascular dysfunction and impaired endogenous fibrinolysis. Circulation. 2005 Dec 20;112(25):3930-6. doi: 10.1161/CIRCULATIONAHA.105.588962.

    PMID: 16365212BACKGROUND

  • Langrish JP, Unosson J, Bosson J, Barath S, Muala A, Blackwell S, Soderberg S, Pourazar J, Megson IL, Treweeke A, Sandstrom T, Newby DE, Blomberg A, Mills NL. Altered nitric oxide bioavailability contributes to diesel exhaust inhalation-induced cardiovascular dysfunction in man. J Am Heart Assoc. 2013 Feb 19;2(1):e004309. doi: 10.1161/JAHA.112.004309.

    PMID: 23525434DERIVED

Study Officials

  • Anders Blomberg, MD PhD

    Umeå University

    PRINCIPAL INVESTIGATOR

  • David E Newby, PhD FRCP

    University of Edinburgh

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Sponsor Type
OTHER

Study Record Dates

First Submitted

February 17, 2009

First Posted

February 18, 2009

Study Start

April 1, 2009

Primary Completion

July 1, 2009

Study Completion

July 1, 2009

Last Updated

October 9, 2009

Record last verified: 2009-10

Locations

SE(1)