Exposure to Environmental Pollution, Non-occupationalGeminozNCT02469428
Epigenetic Effect Modifications With Ozone Exposure on Healthy Volunteers
A study testing Clean air and Ozone in people with Exposure to Environmental Pollution, Non-occupational, run by Environmental Protection Agency (EPA) at 1 site in United States.
Trial summary
The purpose of this protocol is to assess whether epigenetic factors in healthy individuals make a person more or less responsive to lung inflammation following ozone exposures. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Exposure to Environmental Pollution, Non-occupational
- What is being tested?
- Clean air and Ozone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2013to 5 Nov 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Normal baseline 12-lead resting EKG.
- Normal lung function, defined by NHANES III as:
- FVC of > 80 %.
- FEV1 of > 80 %.
- FEV1/FVC ratio of > 80 %.
- Oxygen saturation of > 96 %.
- Ability to complete the exposure exercise regimen without reaching 80% of predicted maximal heart rate.
Who cannot join
- A history of acute and/or chronic illnesses such as diabetes, rheumatological diseases, immunodeficiency state, neurological disease, renal disease, liver disease, endocrinological disease, malignancy, cardiovascular disease, chronic respiratory diseases, and lung cancer.
- Asthma or a history of asthma.
- A Framingham risk score ≥10.
- Women who are pregnant, attempting to become pregnant, or breastfeeding.
- An allergy to any medications which may be used or prescribed in the course of this study.
- Cannot refrain from taking vitamins C or E (or multivitamins which contain Vitamins C or E) for 7 days prior to all visits.
Show all 30Show fewer
- Cannot refrain from taking supplements for 7 days prior to all visits that contain homeopathic/naturopathic medicines or medications which may impact the results of the ozone challenge or interfere with any other medications potentially used in the study. Medications not specifically mentioned here may be reviewed by the investigators and medical staff prior to inclusion in the study.
- Untreated hypertension (≥ 150 systolic or ≥ 90 diastolic blood pressure).
- Dementia.
- Unspecified illnesses, which in the judgment of the investigator or medical staff might increase the risk associated ozone inhalation challenge or exercise.
- A history of skin allergies to adhesives used in securing EKG electrodes.
- Do not understand or speak English.
- Chronic and continuous allergic rhinitis.
- Unable to perform the moderate exercise required for the study.
- Those that are unwilling or unable to refrain from the following medications for the week prior to each exposure: anti-inflammatory agents such as ibuprofen, naproxen, or aspirin.
- Those currently taking or have taken anti-coagulant medication in the week prior to each exposure.
- Currently smoker or has a smoked within the last 2 years, or if you have a smoking history > 1 pack-years or are living with a smoker that smokes inside the house.
- A history of fainting in response to blood being drawn or other medical procedures.
- Unwilling or unable to stay for a suitable observation period after the procedure at the discretion of the physician involved, and not ride a bicycle or motorcycle home.
- You are unwilling or unable to refrain from strenuous exercise for 24 hours prior to and after all visits, consuming caffeine for 12 hours prior to all study visits, using of antihistamines for one week prior to exposures, and drinking alcohol 24 hours before all visits.
- Temporary exclusions:
- Viral upper respiratory tract infection or any acute infection within 6 weeks of bronchoscopy.
- Current exacerbation of allergic rhinitis and or use of antihistamines during one week prior to exposure.
- Recent or recurring exposure to pollutants or irritants.
- Any food or fluids after midnight prior to bronchoscopy.
- FEV1 decrement of >10% from baseline on AM of bronchoscopy.
- Use of aspirin ≥ 81 mg daily, or other nonsteroidal anti-inflammatory drugs within one week of bronchoscopy.
- You are unwilling or unable to take nothing by mouth after midnight the night before bronchoscopy.
- You are unwilling or unable to stay in the local Raleigh/Durham/Chapel Hill area for 24 hours after the procedure.
- Use of other medications will be evaluated on a case-by-case basis. There is the potential that an individual's current medication use will preclude them from participating in the study at the current time, but they may be reassessed and potentially rescheduled for participation at a later time.
Trial locations and contacts
1 site in 1 country.
United States1 site
EPA Human Studies Facility
Chapel Hill, North Carolina, 27514
About this study
The purpose of this protocol is to assess whether epigenetic factors in healthy individuals make a person more or less responsive to lung inflammation following ozone exposures.
Read the detailed description
Controlled human exposure studies to ozone have reported decreases in lung function (Devlin et al. 2012; Kim et al. 2011) and increased inflammation (Kim et al. 2011; Koren et al. 1991; Liu et al. 2009; Romieu et al. 2008). However, the range of response to ozone in healthy young volunteers is an order of magnitude, and if individuals are exposed to ozone some months later they retain their hierarchy on the response curve, suggesting that long-lived factors are responsible. Several studies have demonstrated that polymorphisms in oxidative stress genes such as GSTM1 or NQO1 may be associated with responsiveness to air pollutants (Bergamaschi et al. 2001; Corradi et al. 2002). However, within the past decade, many researchers have started exploring the epigenome as a possible link between exposures to environmental toxicants and disease. Epigenetics refers to non-genetic mechanisms influencing gene expression and phenotype (Cortessis et al. 2012). Commonly studied epigenetic changes include DNA methylation, histone modification, and non-coding RNA expression (i.e. micro-RNA). Recently, work conducted at the Harvard School of Public Health looked at DNA methylation as an effect modifier to air pollution-induced adverse health effects (Bind et al. 2012). This group, using a cohort representing previous war veterans from the VA Normative Aging Study, observed stronger effects in cardiovascular disease-related blood biomarkers with DNA methylation status, both globally and within candidate genes. Additionally, Salam et al. found that fractional exhaled nitric oxide, a marker of lung inflammation, was interrelated with short-term PM 2.5 concentration as well as NOS2 epigenetic and genetic variations in children (2012). Thus, these studies suggest epigenetic changes could impact susceptibility to pollutants. Additionally, acute epigenetic changes, which are potential pathways of air pollution-induced health effects, have been associated with the inhalation of particulate matter and ambient gaseous pollutants (Baccarelli et al. 2009; Bellavia et al. 2013; Bollati et al. 2010; De Prins et al. 2013; Madrigano et al. 2011; Tarantini et al. 2009). Therefore, it is possible that an individual's epigenetic profile could make them more or less responsive to ozone, and that ozone exposure itself could cause acute changes in the epigenome which could in turn affect ozone-responsiveness.
Previous studies that have looked at epigenetic changes associated with air pollutants have difficultly disentangling the role of genetic and epigenetic factors. One way to do this is to study identical (MZ) twins. MZ twins arise when two or more daughter cells split from a single zygote during embryonic development, forming two individuals with identical genetic sequences (Fraga et al. 2005) but dissimilar epigenomes (Li et al. 2013; Szyf 2007). A number of diseases in which MZ twins are discordant, such as bipolar and schizophrenia disorders (Bonsch et al. 2012; Dempster et al. 2011), asthma (Runyon et al. 2012), autism spectrum disorder (Wong et al. 2013), and breast cancer (Heyn et al. 2013), implicate epigenetic variability as the cause. Therefore, as discordance for disease status has already been linked with epigenetic changes, this adds further plausibility to the notion that epigenetics could be responsible for the susceptibility of some subjects to ozone exposures while others seem non-responsive. By using MZ twins as one target population for this study, variability due only to epigenetics, without the influence of genetics, can be fully explored.
For this study, the investigators will measure changes in pulmonary inflammation after a controlled exposure in healthy subjects and healthy twin pairs to clean air and ozone. This endpoint was chosen because previous work has shown that the epithelial cells lining the airways are the first target of ozone and respond by making pro-inflammatory cytokines such as IL-6 and IL-8. Epigenetic changes are dependent on tissue type, and airway epithelial cells can be obtained by brush biopsies during bronchoscopy and assayed for epigenetic changes. The investigators will determine whether differences in baseline epigenetic profiles between subjects are associated with responsiveness to ozone and whether ozone exposure itself causes acute changes in a subject's epigenome.
- Being tested
- Clean air, Ozone
- Keywords
- Controlled human exposure study, Ozone, Inflammation
- Medical subject headings
- Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clean airOther
Each subject will be exposed to clean air for 2 hours. Subjects will exercise on a bike. Each exercise session will consist of a 15 minute exercise interval at a level of up to 20 L/min/m2 BSA followed by a 15 minute rest period, repeated 4 times.
OzoneOther
Each subject will be exposed to 0.3 ppb ozone for 2 hours. Subjects will exercise on a bike. Each exercise session will consist of a 15 minute exercise interval at a level of up to 20 L/min/m2 BSA followed by a 15 minute rest period, repeated 4 times.
| Study group | Role | What they receive |
|---|---|---|
| Clean air | Sham comparator | Exposure to clean air will be conducted in an exposure chamber at the EPA Human Studies Facility on the UNC campus. Receives: Other: Clean air |
| Ozone | Experimental | Exposure to ozone will be conducted in an exposure chamber at the EPA Human Studies Facility on the UNC campus. Receives: Other: Ozone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pulmonary inflammation
18 hrs following exposures the subjects will undergo a research bronchoscopy where lavage fluid and epithelial cells via brush biopsy will be collected. Protein content will be assessed in lavage fluid. Changes in inflammatory genes will be measured in epithelial cells. DNA will be extracted from epithelial cells and DNA methylation arrays will be run.
Measured: pre-exposure to 18 hrs post exposure
Secondary outcomes (5)
Changes in heart rate variability
10 minute electrocardiogram recording (measured by Holter ECG) in which the subject has been resting for 20 minutes prior. Collected on a Mortara H12+ 12-lead ECG recorder. The digitally recorded ECGs are sampled at 180 Hz.
Measured: pre-exposure to 18 hrs post-exposure
Forced expiratory volume in 1 second (FEV1)
FEV1 is determined by spirometry performed on a dry seal spirometer interfaced to a computer.
Measured: pre-exposure to 18 hrs post-exposure
Forced vital capacity (FVC)
FVC is determined by spirometry performed on a dry seal spirometer interfaced to a computer.
Measured: pre-exposure to 18 hrs post-exposure
Index of clotting/coagulation factors
Index of clotting/coagulation factors are the mean percent changes in a variety of clotting/coagulation factors (d-dimer, PA-1, tPA, vWillebrand factor, plasminogen) in the blood.
Measured: pre-exposure to 18 hrs post-exposure
Index of inflammatory factors from blood
Index of inflammatory factors are the mean percent changes in a variety of systemic inflammatory factors (IL-6, IL-8, TNF-a, IL-1b, CRP) in the blood.
Measured: pre-exposure to 18 hrs post-exposure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2015 (estimated)
- Study startDec 2013
- Primary completionJul 2017
- Study completion5 Nov 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (24)Papers the sponsor has linked to this study.
- Other trials for Exposure to Environmental Pollution, Non-occupationalStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Environmental Protection Agency (EPA)
- Sponsor type
- US federal agency
- Responsible party
- Principal investigator, David Diaz-Sanchez, Environmental Protection Agency (EPA)
- Investigators
- David Diaz-Sanchez, PhD, Principal investigator, Environmental Protection Agency (EPA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02469428
- Sponsor's protocol ID
- 13-3697
- Acronym
- Geminoz
- Status last verified
- Jul 2019
- First submitted
- 5 Jun 2015
- Last updated
- 30 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Baccarelli A, Wright RO, Bollati V, Tarantini L, Litonjua AA, Suh HH, Zanobetti A, Sparrow D, Vokonas PS, Schwartz J. Rapid DNA methylation changes after exposure to traffic particles. Am J Respir Crit Care Med. 2009 Apr 1;179(7):572-8. doi: 10.1164/rccm.200807-1097OC. Epub 2009 Jan 8.
PubMed 19136372Bellavia A, Urch B, Speck M, Brook RD, Scott JA, Albetti B, Behbod B, North M, Valeri L, Bertazzi PA, Silverman F, Gold D, Baccarelli AA. DNA hypomethylation, ambient particulate matter, and increased blood pressure: findings from controlled human exposure experiments. J Am Heart Assoc. 2013 Jun 19;2(3):e000212. doi: 10.1161/JAHA.113.000212.
PubMed 23782920Bergamaschi E, De Palma G, Mozzoni P, Vanni S, Vettori MV, Broeckaert F, Bernard A, Mutti A. Polymorphism of quinone-metabolizing enzymes and susceptibility to ozone-induced acute effects. Am J Respir Crit Care Med. 2001 May;163(6):1426-31. doi: 10.1164/ajrccm.163.6.2006056.
PubMed 11371413Bind MA, Baccarelli A, Zanobetti A, Tarantini L, Suh H, Vokonas P, Schwartz J. Air pollution and markers of coagulation, inflammation, and endothelial function: associations and epigene-environment interactions in an elderly cohort. Epidemiology. 2012 Mar;23(2):332-40. doi: 10.1097/EDE.0b013e31824523f0.
PubMed 22237295Bollati V, Marinelli B, Apostoli P, Bonzini M, Nordio F, Hoxha M, Pegoraro V, Motta V, Tarantini L, Cantone L, Schwartz J, Bertazzi PA, Baccarelli A. Exposure to metal-rich particulate matter modifies the expression of candidate microRNAs in peripheral blood leukocytes. Environ Health Perspect. 2010 Jun;118(6):763-8. doi: 10.1289/ehp.0901300. Epub 2010 Jan 8.
PubMed 20061215Bonsch D, Wunschel M, Lenz B, Janssen G, Weisbrod M, Sauer H. Methylation matters? Decreased methylation status of genomic DNA in the blood of schizophrenic twins. Psychiatry Res. 2012 Aug 15;198(3):533-7. doi: 10.1016/j.psychres.2011.09.004. Epub 2012 Oct 25.
PubMed 23102571Corradi M, Alinovi R, Goldoni M, Vettori M, Folesani G, Mozzoni P, Cavazzini S, Bergamaschi E, Rossi L, Mutti A. Biomarkers of oxidative stress after controlled human exposure to ozone. Toxicol Lett. 2002 Aug 5;134(1-3):219-25. doi: 10.1016/s0378-4274(02)00169-8.
PubMed 12191881Cortessis VK, Thomas DC, Levine AJ, Breton CV, Mack TM, Siegmund KD, Haile RW, Laird PW. Environmental epigenetics: prospects for studying epigenetic mediation of exposure-response relationships. Hum Genet. 2012 Oct;131(10):1565-89. doi: 10.1007/s00439-012-1189-8. Epub 2012 Jun 28.
PubMed 22740325De Prins S, Koppen G, Jacobs G, Dons E, Van de Mieroop E, Nelen V, Fierens F, Int Panis L, De Boever P, Cox B, Nawrot TS, Schoeters G. Influence of ambient air pollution on global DNA methylation in healthy adults: a seasonal follow-up. Environ Int. 2013 Sep;59:418-24. doi: 10.1016/j.envint.2013.07.007. Epub 2013 Aug 3.
PubMed 23917442Dempster EL, Pidsley R, Schalkwyk LC, Owens S, Georgiades A, Kane F, Kalidindi S, Picchioni M, Kravariti E, Toulopoulou T, Murray RM, Mill J. Disease-associated epigenetic changes in monozygotic twins discordant for schizophrenia and bipolar disorder. Hum Mol Genet. 2011 Dec 15;20(24):4786-96. doi: 10.1093/hmg/ddr416. Epub 2011 Sep 9.
PubMed 21908516Devlin RB, Duncan KE, Jardim M, Schmitt MT, Rappold AG, Diaz-Sanchez D. Controlled exposure of healthy young volunteers to ozone causes cardiovascular effects. Circulation. 2012 Jul 3;126(1):104-11. doi: 10.1161/CIRCULATIONAHA.112.094359. Epub 2012 Jun 25.
PubMed 22732313Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, Heine-Suner D, Cigudosa JC, Urioste M, Benitez J, Boix-Chornet M, Sanchez-Aguilera A, Ling C, Carlsson E, Poulsen P, Vaag A, Stephan Z, Spector TD, Wu YZ, Plass C, Esteller M. Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10604-9. doi: 10.1073/pnas.0500398102. Epub 2005 Jul 11.
PubMed 16009939Heyn H, Carmona FJ, Gomez A, Ferreira HJ, Bell JT, Sayols S, Ward K, Stefansson OA, Moran S, Sandoval J, Eyfjord JE, Spector TD, Esteller M. DNA methylation profiling in breast cancer discordant identical twins identifies DOK7 as novel epigenetic biomarker. Carcinogenesis. 2013 Jan;34(1):102-8. doi: 10.1093/carcin/bgs321. Epub 2012 Oct 10.
PubMed 23054610Kim CS, Alexis NE, Rappold AG, Kehrl H, Hazucha MJ, Lay JC, Schmitt MT, Case M, Devlin RB, Peden DB, Diaz-Sanchez D. Lung function and inflammatory responses in healthy young adults exposed to 0.06 ppm ozone for 6.6 hours. Am J Respir Crit Care Med. 2011 May 1;183(9):1215-21. doi: 10.1164/rccm.201011-1813OC. Epub 2011 Jan 7.
PubMed 21216881Koren HS, Devlin RB, Becker S, Perez R, McDonnell WF. Time-dependent changes of markers associated with inflammation in the lungs of humans exposed to ambient levels of ozone. Toxicol Pathol. 1991;19(4 Pt 1):406-11. doi: 10.1177/0192623391019004-109.
PubMed 1813985
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Epigenetic Effect Modifications With Ozone Exposure on Healthy Volunteers
- ClinicalTrials.gov ID
- NCT02469428
- Acronym / sponsor ID
- Geminoz / 13-3697
- Keywords
- Controlled human exposure study, Ozone, Inflammation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Environmental Protection Agency (EPA)US federal agency
- Study start
- Dec 2013
- Primary completion
- Jul 2017 (actual)
- Study completion
- 5 Nov 2018 (actual)
- First posted
- 11 Jun 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this protocol is to assess whether epigenetic factors in healthy individuals make a person more or less responsive to lung inflammation following ozone exposures.
Detailed description
Controlled human exposure studies to ozone have reported decreases in lung function (Devlin et al. 2012; Kim et al. 2011) and increased inflammation (Kim et al. 2011; Koren et al. 1991; Liu et al. 2009; Romieu et al. 2008). However, the range of response to ozone in healthy young volunteers is an order of magnitude, and if individuals are exposed to ozone some months later they retain their hierarchy on the response curve, suggesting that long-lived factors are responsible. Several studies have demonstrated that polymorphisms in oxidative stress genes such as GSTM1 or NQO1 may be associated with responsiveness to air pollutants (Bergamaschi et al. 2001; Corradi et al. 2002). However, within the past decade, many researchers have started exploring the epigenome as a possible link between exposures to environmental toxicants and disease. Epigenetics refers to non-genetic mechanisms influencing gene expression and phenotype (Cortessis et al. 2012). Commonly studied epigenetic changes include DNA methylation, histone modification, and non-coding RNA expression (i.e. micro-RNA). Recently, work conducted at the Harvard School of Public Health looked at DNA methylation as an effect modifier to air pollution-induced adverse health effects (Bind et al. 2012). This group, using a cohort representing previous war veterans from the VA Normative Aging Study, observed stronger effects in cardiovascular disease-related blood biomarkers with DNA methylation status, both globally and within candidate genes. Additionally, Salam et al. found that fractional exhaled nitric oxide, a marker of lung inflammation, was interrelated with short-term PM 2.5 concentration as well as NOS2 epigenetic and genetic variations in children (2012). Thus, these studies suggest epigenetic changes could impact susceptibility to pollutants. Additionally, acute epigenetic changes, which are potential pathways of air pollution-induced health effects, have been associated with the inhalation of particulate matter and ambient gaseous pollutants (Baccarelli et al. 2009; Bellavia et al. 2013; Bollati et al. 2010; De Prins et al. 2013; Madrigano et al. 2011; Tarantini et al. 2009). Therefore, it is possible that an individual's epigenetic profile could make them more or less responsive to ozone, and that ozone exposure itself could cause acute changes in the epigenome which could in turn affect ozone-responsiveness.
Previous studies that have looked at epigenetic changes associated with air pollutants have difficultly disentangling the role of genetic and epigenetic factors. One way to do this is to study identical (MZ) twins. MZ twins arise when two or more daughter cells split from a single zygote during embryonic development, forming two individuals with identical genetic sequences (Fraga et al. 2005) but dissimilar epigenomes (Li et al. 2013; Szyf 2007). A number of diseases in which MZ twins are discordant, such as bipolar and schizophrenia disorders (Bonsch et al. 2012; Dempster et al. 2011), asthma (Runyon et al. 2012), autism spectrum disorder (Wong et al. 2013), and breast cancer (Heyn et al. 2013), implicate epigenetic variability as the cause. Therefore, as discordance for disease status has already been linked with epigenetic changes, this adds further plausibility to the notion that epigenetics could be responsible for the susceptibility of some subjects to ozone exposures while others seem non-responsive. By using MZ twins as one target population for this study, variability due only to epigenetics, without the influence of genetics, can be fully explored.
For this study, the investigators will measure changes in pulmonary inflammation after a controlled exposure in healthy subjects and healthy twin pairs to clean air and ozone. This endpoint was chosen because previous work has shown that the epithelial cells lining the airways are the first target of ozone and respond by making pro-inflammatory cytokines such as IL-6 and IL-8. Epigenetic changes are dependent on tissue type, and airway epithelial cells can be obtained by brush biopsies during bronchoscopy and assayed for epigenetic changes. The investigators will determine whether differences in baseline epigenetic profiles between subjects are associated with responsiveness to ozone and whether ozone exposure itself causes acute changes in a subject's epigenome.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Clean air | Sham comparator | Other: Clean airExposure to clean air will be conducted in an exposure chamber at the EPA Human Studies Facility on the UNC campus. |
| Ozone | Experimental | Other: OzoneExposure to ozone will be conducted in an exposure chamber at the EPA Human Studies Facility on the UNC campus. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Normal baseline 12-lead resting EKG.
- Normal lung function, defined by NHANES III as:
- Oxygen saturation of > 96 %.
- Ability to complete the exposure exercise regimen without reaching 80% of predicted maximal heart rate.
Key exclusion criteria (30 listed)
- A history of acute and/or chronic illnesses such as diabetes, rheumatological diseases, immunodeficiency state, neurological disease, renal disease, liver disease, endocrinological disease, malignancy, cardiovascular disease, chronic respiratory diseases, and lung cancer.
- Asthma or a history of asthma.
- A Framingham risk score ≥10.
- Women who are pregnant, attempting to become pregnant, or breastfeeding.
- An allergy to any medications which may be used or prescribed in the course of this study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Clean airEach subject will be exposed to clean air for 2 hours. Subjects will exercise on a bike. Each exercise session will consist of a 15 minute exercise interval at a level of up to 20 L/min/m2 BSA followed by a 15 minute rest period, repeated 4 times. | Other | Clean air |
| OzoneEach subject will be exposed to 0.3 ppb ozone for 2 hours. Subjects will exercise on a bike. Each exercise session will consist of a 15 minute exercise interval at a level of up to 20 L/min/m2 BSA followed by a 15 minute rest period, repeated 4 times. | Other | Ozone |
Primary outcome
Pulmonary inflammation
Time frame: pre-exposure to 18 hrs post exposure
18 hrs following exposures the subjects will undergo a research bronchoscopy where lavage fluid and epithelial cells via brush biopsy will be collected. Protein content will be assessed in lavage fluid. Changes in inflammatory genes will be measured in epithelial cells. DNA will be extracted from epithelial cells and DNA methylation arrays will be run.
5 secondary outcomes
Changes in heart rate variability
Time frame: pre-exposure to 18 hrs post-exposure
Forced expiratory volume in 1 second (FEV1)
Time frame: pre-exposure to 18 hrs post-exposure
Forced vital capacity (FVC)
Time frame: pre-exposure to 18 hrs post-exposure
Index of clotting/coagulation factors
Time frame: pre-exposure to 18 hrs post-exposure
Index of inflammatory factors from blood
Time frame: pre-exposure to 18 hrs post-exposure
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2019.
- Background: PubMed 19136372Baccarelli A, Wright RO, Bollati V, Tarantini L, Litonjua AA, Suh HH, Zanobetti A, Sparrow D, Vokonas PS, Schwartz J. Rapid DNA methylation changes after exposure to traffic particles. Am J Respir Crit Care Med. 2009 Apr 1;179(7):572-8. doi: 10.1164/rccm.200807-1097OC. Epub 2009 Jan 8.
- Background: PubMed 23782920Bellavia A, Urch B, Speck M, Brook RD, Scott JA, Albetti B, Behbod B, North M, Valeri L, Bertazzi PA, Silverman F, Gold D, Baccarelli AA. DNA hypomethylation, ambient particulate matter, and increased blood pressure: findings from controlled human exposure experiments. J Am Heart Assoc. 2013 Jun 19;2(3):e000212. doi: 10.1161/JAHA.113.000212.
- Background: PubMed 11371413Bergamaschi E, De Palma G, Mozzoni P, Vanni S, Vettori MV, Broeckaert F, Bernard A, Mutti A. Polymorphism of quinone-metabolizing enzymes and susceptibility to ozone-induced acute effects. Am J Respir Crit Care Med. 2001 May;163(6):1426-31. doi: 10.1164/ajrccm.163.6.2006056.
- Background: PubMed 22237295Bind MA, Baccarelli A, Zanobetti A, Tarantini L, Suh H, Vokonas P, Schwartz J. Air pollution and markers of coagulation, inflammation, and endothelial function: associations and epigene-environment interactions in an elderly cohort. Epidemiology. 2012 Mar;23(2):332-40. doi: 10.1097/EDE.0b013e31824523f0.
- Background: PubMed 20061215Bollati V, Marinelli B, Apostoli P, Bonzini M, Nordio F, Hoxha M, Pegoraro V, Motta V, Tarantini L, Cantone L, Schwartz J, Bertazzi PA, Baccarelli A. Exposure to metal-rich particulate matter modifies the expression of candidate microRNAs in peripheral blood leukocytes. Environ Health Perspect. 2010 Jun;118(6):763-8. doi: 10.1289/ehp.0901300. Epub 2010 Jan 8.
- Background: PubMed 23102571Bonsch D, Wunschel M, Lenz B, Janssen G, Weisbrod M, Sauer H. Methylation matters? Decreased methylation status of genomic DNA in the blood of schizophrenic twins. Psychiatry Res. 2012 Aug 15;198(3):533-7. doi: 10.1016/j.psychres.2011.09.004. Epub 2012 Oct 25.
- Background: PubMed 12191881Corradi M, Alinovi R, Goldoni M, Vettori M, Folesani G, Mozzoni P, Cavazzini S, Bergamaschi E, Rossi L, Mutti A. Biomarkers of oxidative stress after controlled human exposure to ozone. Toxicol Lett. 2002 Aug 5;134(1-3):219-25. doi: 10.1016/s0378-4274(02)00169-8.
- Background: PubMed 22740325Cortessis VK, Thomas DC, Levine AJ, Breton CV, Mack TM, Siegmund KD, Haile RW, Laird PW. Environmental epigenetics: prospects for studying epigenetic mediation of exposure-response relationships. Hum Genet. 2012 Oct;131(10):1565-89. doi: 10.1007/s00439-012-1189-8. Epub 2012 Jun 28.
- Background: PubMed 23917442De Prins S, Koppen G, Jacobs G, Dons E, Van de Mieroop E, Nelen V, Fierens F, Int Panis L, De Boever P, Cox B, Nawrot TS, Schoeters G. Influence of ambient air pollution on global DNA methylation in healthy adults: a seasonal follow-up. Environ Int. 2013 Sep;59:418-24. doi: 10.1016/j.envint.2013.07.007. Epub 2013 Aug 3.
- Background: PubMed 21908516Dempster EL, Pidsley R, Schalkwyk LC, Owens S, Georgiades A, Kane F, Kalidindi S, Picchioni M, Kravariti E, Toulopoulou T, Murray RM, Mill J. Disease-associated epigenetic changes in monozygotic twins discordant for schizophrenia and bipolar disorder. Hum Mol Genet. 2011 Dec 15;20(24):4786-96. doi: 10.1093/hmg/ddr416. Epub 2011 Sep 9.
- Background: PubMed 22732313Devlin RB, Duncan KE, Jardim M, Schmitt MT, Rappold AG, Diaz-Sanchez D. Controlled exposure of healthy young volunteers to ozone causes cardiovascular effects. Circulation. 2012 Jul 3;126(1):104-11. doi: 10.1161/CIRCULATIONAHA.112.094359. Epub 2012 Jun 25.
- Background: PubMed 16009939Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, Heine-Suner D, Cigudosa JC, Urioste M, Benitez J, Boix-Chornet M, Sanchez-Aguilera A, Ling C, Carlsson E, Poulsen P, Vaag A, Stephan Z, Spector TD, Wu YZ, Plass C, Esteller M. Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10604-9. doi: 10.1073/pnas.0500398102. Epub 2005 Jul 11.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Diaz-Sanchez, PhD principal investigator
Environmental Protection Agency (EPA)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Clean air and Ozone in people with Exposure to Environmental Pollution, Non-occupational, run by Environmental Protection Agency (EPA) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pulmonary inflammation (time frame: pre-exposure to 18 hrs post exposure). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02469428, which also lists 24 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2019.