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

July 31, 2013 updated by: Prof. Dr. Jens Jordan, Hannover Medical School
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Germany
      • Hannover, Germany, 30625
        • Recruiting
        • Hannover Medical School
        • Contact:
        • Sub-Investigator:
          • Marcus May, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

50 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Other: ultrafine particles
exposure to ultrafine particles
Active Comparator: 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.
Other: ultrafine particles and ozone
exposure to ultrafine particles and ozone
Placebo Comparator: 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.
Other: clean air
Exposure to clean air.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Muscle sympathetic nerve activity (MSNA)
Time Frame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
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

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
MSNA burst incidence
Time Frame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
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
total MSNA
Time Frame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
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

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Blood pressure
Time Frame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
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
Heart rate
Time Frame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
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
Cardiac output
Time Frame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
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
Total peripheral resistance
Time Frame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
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
Heart rate variability.
Time Frame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
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
Plasma norepinephrine concentration
Time Frame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
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
Plasma renin concentration
Time Frame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
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
Baroreflex sensitivity
Time Frame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
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
Inflammation parameters
Time Frame: 3.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
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
Oxidative stress parameters
Time Frame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
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
Correlation between inflammation, oxidative stress and cardiovascular regulation
Time Frame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
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
Forced expiratory volume in one second (FEV1)
Time Frame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
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
Forced vital capacity (FVC)
Time Frame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
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
Percentage of neutrophils in peripheral blood
Time Frame: 2.5 hours after exposure to clean air, to ultrafine particles, or to a combination of ultrafine particles and ozone
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hannover Medical School

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Fraunhofer-Institute of Toxicology and Experimental Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2013

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2015

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 30, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 31, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 2, 2013

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 2, 2013

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 31, 2013

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2013

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MHH-Particles EK-6142

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