Diesel Exhaust Inhalation, Systemic Nitric Oxide Inhibition and Cardiac Output

Vascular Function in Healthy Volunteers Clinical Trial

— DISCO  

Official title:

Diesel Exhaust Inhalation, Systemic Nitric Oxide Inhibition and Cardiac Output

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01060930
• Other study ID #: DISCO
• Status: Completed
• Phase: N/A
• First received: January 28, 2010
• Last updated: December 15, 2011
• Start date: March 2010
• Est. completion date: June 2010

Study information

• Verified date: April 2011
• Source: University of Edinburgh
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Regional Ethical Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: June 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Vascular Function in Healthy Volunteers

Intervention

Drug:
• Intravenous infusion of L-NMMA and Nor-epinephrine
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.

Locations

Country	Name	City	State
Sweden	University Hospital Umeå	Umeå

Sponsors (3)

Lead Sponsor	Collaborator
University of Edinburgh	NHS Lothian, Umeå University

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Blood pressure response to NO inhibition		Blood pressure will be measured continuously through the vascular study using intra-arterial monitoring	No
Secondary	Heart rate response to systemic nitric oxide inhibition		Heart rate will be measured continuously throughout the study period using continous electrocardiography	No
Secondary	Central arterial stiffness following NO inhibition		Measured at baseline, and every 5 minutes during the 2-hour vascular study	No
Secondary	Cardiac output during NO inhibition		Measured at baseline, and every 5 minutes during the 2-hour vascular study	No
Secondary	Plasma nitrite (NO) concentrations		Measured at baseline, and every 15 minutes during the 2-hour vascular study	No
Secondary	Platelet activation and platelet-monocyte binding		Measured at baseline, and every 30 minutes during the 2-hour vascular study	No
Secondary	Heart rate variability		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	No