Clinical trial NCT01914783: Experimental Exposure to Air Pollutants and Sympathetic Nerve Activity in Human Subjects
Official title: Experimental Exposure to Air Pollutants and Sympathetic Nerve Activity in Human Subjects
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Cardiovascular Morbidity
Keywords: air pollution
ozone
fine particle
cytokine
chemokine
oxidative stress
inflammation
heart rate variability
autonomic nervous system
sympathetic nerve activity
plasma catecholamine
Lead sponsor: Hannover Medical School
Sponsor class: OTHER
Collaborators: name: Fraunhofer-Institute of Toxicology and Experimental Medicine
First posted: 2013-08-02
Enrollment: 30
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: SUPPORTIVE_CARE

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Muscle sympathetic nerve activity (MSNA)
timeFrame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
Secondary outcomes:
measure: MSNA burst incidence
timeFrame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
measure: total MSNA
timeFrame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
Other outcomes:
measure: Blood pressure
timeFrame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
measure: Heart rate
timeFrame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
measure: Cardiac output
timeFrame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
measure: Total peripheral resistance
timeFrame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
measure: Heart rate variability.
timeFrame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
measure: Plasma norepinephrine concentration
timeFrame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
measure: Plasma renin concentration
timeFrame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
measure: Baroreflex sensitivity
timeFrame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
measure: Inflammation parameters
timeFrame: 3.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
measure: Oxidative stress parameters
timeFrame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
measure: Correlation between inflammation, oxidative stress and cardiovascular regulation
timeFrame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
measure: Forced expiratory volume in one second (FEV1)
timeFrame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
measure: Forced vital capacity (FVC)
timeFrame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
measure: Percentage of neutrophils in peripheral blood
timeFrame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
Locations:
city: Hannover
country: Germany
facility: Hannover Medical School
Study officials:
References:
citation: 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.