Back to results

Diesel Exhaust Inhalation, Systemic Nitric Oxide Inhibition and Cardiac Output (DISCO)

Primary Purpose

Vascular Function in Healthy Volunteers

Status

Completed

Phase

Not Applicable

Locations

Sweden

Study Type

Interventional

Intervention

Intravenous infusion of L-NMMA and Nor-epinephrine

About this trial

This is an interventional basic science trial for Vascular Function in Healthy Volunteers focused on measuring Nitric oxide, Diesel exhaust, Air pollution, Cardiac output, Healthy volunteers

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Healthy volunteers
Non smokers
No regular medication (except oral contraceptive)
No recent respiratory tract infection (within 6 weeks)

Exclusion Criteria:

History of asthma or respiratory disease
Smoking history
Pregnancy (positive urinary pregnancy test)

Sites / Locations

University Hospital Umeå

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Diesel exhaust exposure

Air exposure

Arm Description

1 hour exposure to dilute diesel exhaust ~ 300 mcg/m3 - during intermittent exercise

1 hour exposure to filtered air during intermittent exercise

Outcomes

Primary Outcome Measures

Blood pressure response to NO inhibition

Secondary Outcome Measures

Heart rate response to systemic nitric oxide inhibition

Central arterial stiffness following NO inhibition

Cardiac output during NO inhibition

Plasma nitrite (NO) concentrations

Platelet activation and platelet-monocyte binding

Heart rate variability

Full Information

NCT ID

NCT01060930

First Posted

January 28, 2010

Last Updated

December 15, 2011

Sponsor

University of Edinburgh

Collaborators

NHS Lothian, Umeå University

1. Study Identification

Unique Protocol Identification Number

NCT01060930

Brief Title

Diesel Exhaust Inhalation, Systemic Nitric Oxide Inhibition and Cardiac Output

Acronym

DISCO

Official Title

Diesel Exhaust Inhalation, Systemic Nitric Oxide Inhibition and Cardiac Output

Study Type

Interventional

2. Study Status

Record Verification Date

April 2011

Overall Recruitment Status

Completed

Study Start Date

March 2010 (undefined)

Primary Completion Date

June 2010 (Actual)

Study Completion Date

June 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Edinburgh

Collaborators

NHS Lothian, Umeå University

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Exposure to combustion-derived fine particulate air pollution is associated with cardiovascular mortality and morbidity. In previous studies, exposure to diesel exhaust (a major constituent of urban particulate air pollution) has been shown to impair two important functions of the vascular endothelium: vascular vasomotor function and endogenous fibrinolysis. Our subsequent studies suggest this impairment of vascular function is mediated by a reduction in nitric oxide bioavailability. In this study we aim to investigate the cardiovascular responses to systemic nitric oxide synthase inhibition following exposure to dilute diesel exhaust.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Vascular Function in Healthy Volunteers

Keywords

Nitric oxide, Diesel exhaust, Air pollution, Cardiac output, Healthy volunteers

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

14 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Diesel exhaust exposure

Arm Type

Experimental

Arm Description

1 hour exposure to dilute diesel exhaust ~ 300 mcg/m3 - during intermittent exercise

Arm Title

Air exposure

Arm Type

Experimental

Arm Description

1 hour exposure to filtered air during intermittent exercise

Intervention Type

Drug

Intervention Name(s)

Intravenous infusion of L-NMMA and Nor-epinephrine

Other Intervention Name(s)

L-NMMA: Clinalfa Basic, Bachem, Germany

Intervention Description

Intravenous infusion of 3mg/kg L-NMMA (L-NG-monomethyl arginine; NO synthase inhibitor) and nor-epinephrine at 50 ng/kg/min. Each infusion to run over 15 mins and separated by 45 min to allow return to baseline. Drugs infused in a randomised order. During the study, blood pressure will be measured invasively using an intra-arterial radial artery cannula, central arterial stiffness measured using peripheral arterial tonometry and cardiac output using thoracic bioimpedance.

Primary Outcome Measure Information:

Title

Blood pressure response to NO inhibition

Time Frame

Blood pressure will be measured continuously through the vascular study using intra-arterial monitoring

Secondary Outcome Measure Information:

Title

Heart rate response to systemic nitric oxide inhibition

Time Frame

Heart rate will be measured continuously throughout the study period using continous electrocardiography

Title

Central arterial stiffness following NO inhibition

Time Frame

Measured at baseline, and every 5 minutes during the 2-hour vascular study

Title

Cardiac output during NO inhibition

Time Frame

Measured at baseline, and every 5 minutes during the 2-hour vascular study

Title

Plasma nitrite (NO) concentrations

Time Frame

Measured at baseline, and every 15 minutes during the 2-hour vascular study

Title

Platelet activation and platelet-monocyte binding

Time Frame

Measured at baseline, and every 30 minutes during the 2-hour vascular study

Title

Heart rate variability

Time Frame

Heart rate will be measured continuously throughout the study period using continous electrocardiography, and HRV subsequently determined for the whole study period and the 2-hour vascular study separately

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Healthy volunteers Non smokers No regular medication (except oral contraceptive) No recent respiratory tract infection (within 6 weeks) Exclusion Criteria: History of asthma or respiratory disease Smoking history Pregnancy (positive urinary pregnancy test)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jeremy P Langrish, MB BCh MRCP

Organizational Affiliation

University of Edinburgh

Official's Role

Principal Investigator

Facility Information:

Facility Name

University Hospital Umeå

City

Umeå

Country

Sweden

12. IPD Sharing Statement

Citations:

PubMed Identifier

23525434

Citation

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.

Results Reference

derived

Learn more about this trial

Diesel Exhaust Inhalation, Systemic Nitric Oxide Inhibition and Cardiac Output

We'll reach out to this number within 24 hrs