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

NCT ID: NCT01914783

Last Updated: 2013-08-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-07-31

Study Completion Date

2015-12-31

Brief Summary

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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

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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.

Conditions

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Cardiovascular Morbidity

Keywords

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air pollution ozone fine particle cytokine chemokine oxidative stress inflammation heart rate variability autonomic nervous system sympathetic nerve activity plasma catecholamine

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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ultrafine particles

Subjects will be exposed to ultrafine particles for three hours in an exposure chamber. During that time participants will perform intermittent bicycle ergometer training. Training intensity is adjusted individually to increase ventilation to 20 l/min/m². During exposure, heart rate will be monitored continuously via ECG. Blood pressure will be measured every 15 minutes. Ultrafine elemental carbon black particles are generated using a commercially available electric spark generator. Particle number, mass, and size distribution will be monitored during exposure.

Group Type EXPERIMENTAL

ultrafine particles

Intervention Type OTHER

exposure to ultrafine particles

ultrafine particles and ozone

Subjects will be exposed to ultrafine particles for three hours in an exposure chamber. During that time participants will perform intermittent bicycle ergometer training. Training intensity is adjusted individually to increase ventilation to 20 l/min/m². During exposure, heart rate will be monitored continuously via ECG. Blood pressure will be measured every 15 minutes. Ultrafine elemental carbon black particles are generated using a commercially available electric spark generator. Particle number, mass, and size distribution will be monitored during exposure.Ozone is generated from medical oxygen in order to maintain a concentration of 250 ppb.

Group Type ACTIVE_COMPARATOR

ultrafine particles and ozone

Intervention Type OTHER

exposure to ultrafine particles and ozone

clean air

Subjects will be exposed to clean air for three hours in an exposure chamber controlled for temperature, humidity, and gas/particle composition. During that time they will perform intermittent bicycle ergometer training for 15 minutes alternating with 15 minutes rest. Training intensity is adjusted individually to increase ventilation to 20 l/min/m². During exposure, heart rate will be monitored continuously via ECG. The blood pressure will be measured in time intervals of 15 minutes.

Group Type PLACEBO_COMPARATOR

clean air

Intervention Type OTHER

Exposure to clean air.

Interventions

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ultrafine particles

exposure to ultrafine particles

Intervention Type OTHER

ultrafine particles and ozone

exposure to ultrafine particles and ozone

Intervention Type OTHER

clean air

Exposure to clean air.

Intervention Type OTHER

Eligibility Criteria

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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.
Minimum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Fraunhofer-Institute of Toxicology and Experimental Medicine

OTHER

Sponsor Role collaborator

Hannover Medical School

OTHER

Sponsor Role lead

Responsible Party

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Prof. Dr. Jens Jordan

Professor Dr. med. Jens Jordan

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Hannover Medical School

Hanover, , Germany

Site Status RECRUITING

Countries

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Germany

Central Contacts

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Marcus May, MD

Role: CONTACT

Phone: +49 511 532

Email: [email protected]

Facility Contacts

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Marcus May, MD

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 21494635 (View on PubMed)

Other Identifiers

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MHH-Particles EK-6142

Identifier Type: -

Identifier Source: org_study_id