Experimental Exposure to Air Pollutants and Sympathetic Nerve Activity in Human Subjects

Cardiovascular Morbidity Clinical Trial

— Particles  

Official title:

Experimental Exposure to Air Pollutants and Sympathetic Nerve Activity in Human Subjects

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01914783
• Other study ID #: MHH-Particles EK-6142
• Status: Recruiting
• Phase: N/A
• First received: July 30, 2013
• Last updated: July 31, 2013
• Start date: July 2013
• Est. completion date: December 2015

Study information

• Verified date: July 2013
• Source: Hannover Medical School
• Contact: Marcus May, MD
• Phone: +49 511 532
• Email: may.marcus[@]mh-hannover.de
• Is FDA regulated: No
• Health authority: Germany: Ethics CommissionGermany: Federal Ministry of Education and Research
• Study type: Interventional

Clinical Trial Summary

The primary hypothesis of the study is that in healthy elderly subjects experimental exposure to air pollutants increases sympathetic nervous system activity compared with sham (clean air) exposure. The secondary hypothesis of the study is that combined experimental exposure to air pollutants (particles + ozone) increases sympathetic nervous system activity to a greater extent than does the exposure to particles alone.

Description:

In a randomized, double-blind, and cross-over fashion, the participants will be exposed to clean air, ultrafine particles, or ultrafine particles and ozone in an exposure chamber. The investigators will determine blood pressure, heart rate, respiration as well as cardiac output and directly record sympathetic vasomotor tone using the microneurography technique. To elucidate the underlying mechanisms through which particles and ozone affect the autonomic nervous system, the investigators will assess the local and systemic inflammatory response as well as the changes in neurotrophic factors in sputum and blood. In addition, the activation of inflammatory cells in sputum and blood will be analyzed at different points in time after exposures. Changes in sympathetic activity will be correlated with the degree of airway inflammation and oxidative stress assessed in induced sputum and blood. This study will provide important insight in the mechanisms through which air pollution, particularly ultrafine particle exposure, increases cardiovascular risk in human subjects and generate a human model for mechanistic and therapeutic studies.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• Elderly man or postmenopausal woman older than 50 years of age.

• Signed written informed consent.

Exclusion Criteria:

• Smoker.

• Cardiovascular and/or pulmonary disease.

• Medication with relevant impact on autonomic system function, e. g. norepinephrine reuptake inhibitors. Stable medication with slight to moderate autonomic effects is tolerable.

• Subject is the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol.

• Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study.

• Subject unlikely to comply with protocol, e. g. uncooperative attitude or unlikelihood of completing the study.

• Known hypersensitivity to ozone.

• History of drug or alcohol abuse. Particles Study - Protocol version: October 19, 2012 14

• Blood donation of more than 500 mL during the previous 3 months.

Study Design

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

Related Conditions & MeSH terms

• Cardiovascular Morbidity

Intervention

Other:
• ultrafine particles
exposure to ultrafine particles
• ultrafine particles and ozone
exposure to ultrafine particles and ozone
• clean air
Exposure to clean air.

Locations

Country	Name	City	State
Germany	Hannover Medical School	Hannover

Sponsors (2)

Lead Sponsor	Collaborator
Hannover Medical School	Fraunhofer-Institute of Toxicology and Experimental Medicine

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Tank J, Biller H, Heusser K, Holz O, Diedrich A, Framke T, Koch A, Grosshennig A, Koch W, Krug N, Jordan J, Hohlfeld JM. Effect of acute ozone induced airway inflammation on human sympathetic nerve traffic: a randomized, placebo controlled, crossover study. PLoS One. 2011 Apr 8;6(4):e18737. doi: 10.1371/journal.pone.0018737. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Blood pressure	Change of blood pressure in mmHg.	2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone	No
Other	Heart rate	Change of heart rate in beat per minute.	2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone	No
Other	Cardiac output	Change of cardiac output in l/min.	2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone	No
Other	Total peripheral resistance	Change in total peripheral resistance expressed as dyn*s/cm^5.	2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone	No
Other	Heart rate variability.	Change in heart rate variability parameters in the time and frequency domain.	2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone	No
Other	Plasma norepinephrine concentration	Change of plasma norepinephrine in ng/l.	2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone	No
Other	Plasma renin concentration	Change of plasma renin concentration in	2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone	No
Other	Baroreflex sensitivity	Change in baroreflex sensitivity expressed as ms/mmHg.	2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone	No
Other	Inflammation parameters	Change of the percentage of neutrophils in induced sputum.	3.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone	No
Other	Oxidative stress parameters	Change of plasma malondialdehyde(MDA)concentration.	2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone	No
Other	Correlation between inflammation, oxidative stress and cardiovascular regulation	Correlation coefficients between changes in parameters for inflammation and oxidative stress with changes in cardiovascular parameters.	2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone	No
Other	Forced expiratory volume in one second (FEV1)	Change in FEV1 in l	2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone	No
Other	Forced vital capacity (FVC)	Change in FVC in l.	2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone	No
Other	Percentage of neutrophils in peripheral blood	Change of percentage of neutrophils in peripheral blood.	2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone	No
Primary	Muscle sympathetic nerve activity (MSNA)	Change of sympathetic vasoconstrictor nerve activity directed to skeletal muscle expressed as sympathetic bursts per minute. The primary hypothesis of the study is that in healthy elderly subjects experimental exposure to air pollutants increases sympathetic nervous system activity compared with sham (clean air) exposure.	2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone	No
Secondary	MSNA burst incidence	Change of MSNA expressed as bursts/100 heart beats.	2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone	No
Secondary	total MSNA	Change of MSNA expressed as burst area/min.	2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone	No