Heart RatePhase 1EPI-AirNCT01864824
Air Pollution, Epigenetics and Cardiovascular Health: A Human Intervention Trial
A Phase 1 study testing methyl donor in people with Heart Rate and Heart Rate Variability, run by Harvard School of Public Health (HSPH) at 1 site in Canada.
Trial summary
In this study, the pills formulated are being used to try to ameliorate the effect of air pollution on epigenetic changes, specifically DNA methylation, potentially linked with particulate matter air pollution inhalation and cardiovascular health effects. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Heart Rate, Heart Rate Variability, Inflammation
- What is being tested?
- methyl donor
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteCanada
- Study dates
- Jun 2013to Jul 2014
- Phase
- Phase 1
- 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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy volunteer
- Age 18-60 years old
- Non-smoker
- must be able to fast 8 hours prior to exposure visits and for a further 4 hours during the exposure
Who cannot join
- Subjects must not be regularly taking multivitamins, vitamins C \& E, folate, medications, fish oil or aspirin, oral or inhaled steroids, for 4 weeks before and during the trial.
- Lipid abnormalities
- Asthma or respiratory disease
- Hypertension (Bp> 140/90) or taking any blood pressure drug
- Known cardiac disease
- abnormal homocysteine or glucose levels
Trial locations and contacts
1 site in 1 country.
Canada1 site
Gage Occupational and Environmental Health St. Michael's Hospital/University of Toronto
Toronto, Ontario, M5T 1R4
About this study
In this study, the pills formulated are being used to try to ameliorate the effect of air pollution on epigenetic changes, specifically DNA methylation, potentially linked with particulate matter air pollution inhalation and cardiovascular health effects. The way in which this is achieved is that the vitamins, which act as methyl donors, add a methyl group to the DNA to reverse the loss observed on exposure to air pollution.
Specifically for this study, the methyl donor supplement has been made by Jamieson Laboratories, and consists of 50mg Vitamin B6 and 1 mg Vitamin B12, (both within Health Canada approved limits) and 2.5 mg folic acid. The non-vitamin ingredients are those commonly used in pill formation. However, the folic acid concentration is 2.5mg, which is above the 1.0mg limit set by Health Canada for a natural health product. This concentration, however, has been used in previous academic studies safely and effectively, and was also formulated by Jamieson Laboratories. (ClinicalTrials.gov number, NCT00106886; Current Controlled Trials number, ISRCTN14017017. HOPE2 study).
Read the detailed description
Air pollution is a pervasive environmental threat estimated to cause ~800,000 deaths every year worldwide, mostly due to cardiovascular disease. This proposal addresses a fundamental mechanistic and pharmacologic question about effects of air pollution, which can most effectively be addressed through controlled human exposure experiments: does exposure have epigenetic effects that may have downstream subclinical or clinical consequences, and can adverse effects be safely reduced pharmacologically? Consistent evidence from in- vitro and human studies have shown that exposure to air particulate matter pollution (PM, i.e., fine particles) induces hypomethylation of the DNA, an epigenetic process that can underlie the activation of inflammatory genes and is postulated to link inhalation of PM into the lungs with cardiovascular inflammation and adverse responses. Our goal is to determine whether a pharmacological intervention with methyl-donors (i.e., folic acid, Vitamins B6 \& B12, betaine, methionine, and choline) can avert this DNA methylation loss and mitigate the cardiovascular effects induced by PM exposure. The investigators will use experiments of human controlled exposure to PM - which reproduce conditions of exposure similar to those found in real life in urban environments - to conduct a double-blind, placebo-controlled crossover study. The investigators will test whether pharmacological intervention with methyl-donors attenuates the effects of PM exposure on DNA methylation (Aim 1), mRNA expression \& plasma cytokines (Aim 2), and blood pressure, arterial vasoconstriction, endothelial function, and autonomic control of the heart (Aim 3). The investigators' study is poised to be the first human investigation to translate a wealth of animal data showing that methyl-donors can be used to modulate epigenetic states and avert environmental effects. The investigators have a unique opportunity to achieve this goal because we have access to one of the few facilities worldwide for human controlled-exposure studies, as well as to state-of-the-art resources for epigenetics investigations. The investigators will examine DNA methylation and mRNA expression in T-helper cells from human individuals, a cell type with key roles in determining adverse hypertensive and endothelial responses, as shown in several animal models. The investigators will test the effects of methyl-donors on a battery of cardiovascular endpoints that are highly sensitive to PM exposure. The investigators will explore the use of advanced statistical methods for mediation analyses to understand the relationships among PM, DNA methylation, RNA expression, plasma cytokines, and cardiovascular endpoints. The study will be conducted by an investigative team that has conducted seminal work in all of the research areas on which this proposal is built upon, including environmental epigenetics, cardiovascular effects of PM, and human controlled exposure studies.
- Conditions
- Heart Rate, Heart Rate Variability, Inflammation
- Being tested
- methyl donor, Placebo
- Keywords
- air pollution, particulate matter 2.5 (PM2.5), methyl donor, DNA methylation, mRNA, epigenetics, controlled human exposures, cardiovascular responses
- Medical subject headings
- Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
methyl donorDrug
Also called Vitamin B6, Vitamin B12, Folic Acid, Placebo
The design will include a 2 week placebo run-in followed by a baseline blank study (2-hrs exposure to medical air) to provide benchmarks for all assessed variables. Participants will then receive a 4-week placebo treatment before the first PM2.5 exposure study. A 4-week methyl-donor treatment (Dose: 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12 once a day) will precede the 2nd PM2.5 exposure.
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| methyl donor | Experimental | Methyl donor is made up of:
2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12 The design will include a 2 week placebo run-in followed by a baseline blank study (2-hrs exposure to medical air) to provide benchmarks for all assessed variables. Participants will then receive a 4-week placebo treatment before the first PM2.5 exposure study. A 4-week methyl-donor treatment (Dose: 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12 once a day) will precede the 2nd PM2.5 exposure. Receives: Drug: methyl donor |
| placebo | Placebo comparator | placebo: The design will include a 2 week placebo run-in followed by a baseline blank study (2-hrs exposure to medical air) to provide benchmarks for all assessed variables. Participants will then receive a 4-week placebo treatment before the first PM2.5 exposure study. A 4-week methyl-donor treatment (Dose: 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12 once a day) will precede the 2nd PM2.5 exposure. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
DNA methylation in circulating T-helper lymphocytes of six candidate genes (TNFa, TGFb, IFNg, IL17, IL2, IL6)
Blood will be collected from venous phlebotomy and processed for Th-cell isolation within 4hrs. DNA extraction will be performed manually on fresh unfrozen cells. DNA methylation analyses will be conducted using bisulfite-polymerase chain reaction-pyrosequencing. To select target sequences within each gene, we will rely both on assays from previous investigations and bioinformatic analysis using information from the genome browser on transcription factor binding sites conserved in the human/mouse/rat alignment, histone marks associated with active regulatory sequences and gene accessibility, and nucleosome occupancy. We will validate all assays using a titration curve of 0%-100% methylated DNA. Batch effect will be controlled by: a) using 0%, 50%, 100% methylation and universal DNA in each plate; b) running all samples from the same volunteer in one plate. We will intersperse 5% blind duplicates to test reproducibility. All samples will be assayed in duplicate runs.
Measured: 2 years
Secondary outcomes (1)
Blood pressure (BP) , brachial artery diameter (BAD), endothelium-dependent flow-mediated dilation (ED-FMD) and heart rate variability (HRV).
BP will be measured at 30-min intervals during exposure using an automated oscillometric ambulatory monitor secured on the upper left arm. Three BP measures will be taken at each time point separated by 1 minute, and the mean of the 2nd and 3rd measures used. BAD, FMD and nitroglycerin-mediated dilatation will be measured using a Terason 2000 ultrasound with a 7.5-10.0 megahertz linear array transducer. Peak FMD within this period will be used as our primary study outcome for endothelial function. Continuous EKG monitoring will be performed using high-resolution digital 12-lead Holter monitors. Holter monitoring will take place for 24-hr periods which will include before (pre-exposure testing), during the 2-hr exposure and post exposure (just after and 24-hrs post). Immediately prior to exposure, after the exposure and 24 hrs later, we will collect 10-minute resting supine HRV readings. HRV will be evaluated on 5-min ECG data using standardized techniques.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2013 (estimated)
- Study startJun 2013
- Primary completionJul 2014
- Study completionJul 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Heart RateStudies 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 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Harvard School of Public Health (HSPH)
- Sponsor type
- University, hospital or other
- Collaborators
- University of Toronto, Unity Health Toronto
- Responsible party
- Principal investigator, Andrea Baccarelli, Harvard School of Public Health (HSPH)
- Investigators
- Andrea Baccarelli, MD PHD MPH, Principal investigator, HSPHFrances Silverman, PHD, Study director, Unity Health TorontoDiane R. Gold, MD, Study chair, HSPH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01864824
- Sponsor's protocol ID
- 1R21ES021895-01
- Acronym
- EPI-Air
- Status last verified
- May 2017
- First submitted
- 8 May 2013
- Last updated
- 11 May 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Brook RD, Rajagopalan S, Pope CA 3rd, Brook JR, Bhatnagar A, Diez-Roux AV, Holguin F, Hong Y, Luepker RV, Mittleman MA, Peters A, Siscovick D, Smith SC Jr, Whitsel L, Kaufman JD; American Heart Association Council on Epidemiology and Prevention, Council on the Kidney in Cardiovascular Disease, and Council on Nutrition, Physical Activity and Metabolism. Particulate matter air pollution and cardiovascular disease: An update to the scientific statement from the American Heart Association. Circulation. 2010 Jun 1;121(21):2331-78. doi: 10.1161/CIR.0b013e3181dbece1. Epub 2010 May 10.
PubMed 20458016O'Toole TE, Conklin DJ, Bhatnagar A. Environmental risk factors for heart disease. Rev Environ Health. 2008 Jul-Sep;23(3):167-202. doi: 10.1515/reveh.2008.23.3.167.
PubMed 19119685Zanobetti A, Canner MJ, Stone PH, Schwartz J, Sher D, Eagan-Bengston E, Gates KA, Hartley LH, Suh H, Gold DR. Ambient pollution and blood pressure in cardiac rehabilitation patients. Circulation. 2004 Oct 12;110(15):2184-9. doi: 10.1161/01.CIR.0000143831.33243.D8. Epub 2004 Oct 4.
PubMed 15466639Brook RD, Rajagopalan S. Particulate matter, air pollution, and blood pressure. J Am Soc Hypertens. 2009 Sep-Oct;3(5):332-50. doi: 10.1016/j.jash.2009.08.005.
PubMed 20409976Brook RD, Bard RL, Burnett RT, Shin HH, Vette A, Croghan C, Phillips M, Rodes C, Thornburg J, Williams R. Differences in blood pressure and vascular responses associated with ambient fine particulate matter exposures measured at the personal versus community level. Occup Environ Med. 2011 Mar;68(3):224-30. doi: 10.1136/oem.2009.053991. Epub 2010 Oct 8.
PubMed 20935292Liu L, Ruddy T, Dalipaj M, Poon R, Szyszkowicz M, You H, Dales RE, Wheeler AJ. Effects of indoor, outdoor, and personal exposure to particulate air pollution on cardiovascular physiology and systemic mediators in seniors. J Occup Environ Med. 2009 Sep;51(9):1088-98. doi: 10.1097/JOM.0b013e3181b35144.
PubMed 19701101O'Neill MS, Veves A, Zanobetti A, Sarnat JA, Gold DR, Economides PA, Horton ES, Schwartz J. Diabetes enhances vulnerability to particulate air pollution-associated impairment in vascular reactivity and endothelial function. Circulation. 2005 Jun 7;111(22):2913-20. doi: 10.1161/CIRCULATIONAHA.104.517110. Epub 2005 May 31.
PubMed 15927967Baccarelli A, Cassano PA, Litonjua A, Park SK, Suh H, Sparrow D, Vokonas P, Schwartz J. Cardiac autonomic dysfunction: effects from particulate air pollution and protection by dietary methyl nutrients and metabolic polymorphisms. Circulation. 2008 Apr 8;117(14):1802-9. doi: 10.1161/CIRCULATIONAHA.107.726067. Epub 2008 Mar 31.
PubMed 18378616Adar SD, Gold DR, Coull BA, Schwartz J, Stone PH, Suh H. Focused exposures to airborne traffic particles and heart rate variability in the elderly. Epidemiology. 2007 Jan;18(1):95-103. doi: 10.1097/01.ede.0000249409.81050.46.
PubMed 17149139Zhong J, Trevisi L, Urch B, Lin X, Speck M, Coull BA, Liss G, Thompson A, Wu S, Wilson A, Koutrakis P, Silverman F, Gold DR, Baccarelli AA. B-vitamin Supplementation Mitigates Effects of Fine Particles on Cardiac Autonomic Dysfunction and Inflammation: A Pilot Human Intervention Trial. Sci Rep. 2017 Apr 3;7:45322. doi: 10.1038/srep45322.
PubMed 28367952Zhong J, Karlsson O, Wang G, Li J, Guo Y, Lin X, Zemplenyi M, Sanchez-Guerra M, Trevisi L, Urch B, Speck M, Liang L, Coull BA, Koutrakis P, Silverman F, Gold DR, Wu T, Baccarelli AA. B vitamins attenuate the epigenetic effects of ambient fine particles in a pilot human intervention trial. Proc Natl Acad Sci U S A. 2017 Mar 28;114(13):3503-3508. doi: 10.1073/pnas.1618545114. Epub 2017 Mar 13.
PubMed 28289216Zhong J, Urch B, Speck M, Coull BA, Koutrakis P, Thorne PS, Scott J, Liu L, Brook RD, Behbod B, Gibson H, Silverman F, Mittleman MA, Baccarelli AA, Gold DR. Endotoxin and beta-1,3-d-Glucan in Concentrated Ambient Particles Induce Rapid Increase in Blood Pressure in Controlled Human Exposures. Hypertension. 2015 Sep;66(3):509-16. doi: 10.1161/HYPERTENSIONAHA.115.05342. Epub 2015 Jun 29.
PubMed 26123683
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Air Pollution, Epigenetics and Cardiovascular Health: A Human Intervention Trial
- ClinicalTrials.gov ID
- NCT01864824
- Acronym / sponsor ID
- EPI-Air / 1R21ES021895-01
- Conditions
- Heart Rate, Heart Rate Variability, Inflammation
- Keywords
- air pollution, particulate matter 2.5 (PM2.5), methyl donor, DNA methylation, mRNA, epigenetics, controlled human exposures, cardiovascular responses
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Harvard School of Public Health (HSPH)University, hospital or other
- Collaborators
- University of Toronto, Unity Health Toronto
- Study start
- Jun 2013
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 30 May 2013 (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.
In this study, the pills formulated are being used to try to ameliorate the effect of air pollution on epigenetic changes, specifically DNA methylation, potentially linked with particulate matter air pollution inhalation and cardiovascular health effects. The way in which this is achieved is that the vitamins, which act as methyl donors, add a methyl group to the DNA to reverse the loss observed on exposure to air pollution.
Specifically for this study, the methyl donor supplement has been made by Jamieson Laboratories, and consists of 50mg Vitamin B6 and 1 mg Vitamin B12, (both within Health Canada approved limits) and 2.5 mg folic acid. The non-vitamin ingredients are those commonly used in pill formation. However, the folic acid concentration is 2.5mg, which is above the 1.0mg limit set by Health Canada for a natural health product. This concentration, however, has been used in previous academic studies safely and effectively, and was also formulated by Jamieson Laboratories. (ClinicalTrials.gov number, NCT00106886; Current Controlled Trials number, ISRCTN14017017. HOPE2 study).
Detailed description
Air pollution is a pervasive environmental threat estimated to cause ~800,000 deaths every year worldwide, mostly due to cardiovascular disease. This proposal addresses a fundamental mechanistic and pharmacologic question about effects of air pollution, which can most effectively be addressed through controlled human exposure experiments: does exposure have epigenetic effects that may have downstream subclinical or clinical consequences, and can adverse effects be safely reduced pharmacologically? Consistent evidence from in- vitro and human studies have shown that exposure to air particulate matter pollution (PM, i.e., fine particles) induces hypomethylation of the DNA, an epigenetic process that can underlie the activation of inflammatory genes and is postulated to link inhalation of PM into the lungs with cardiovascular inflammation and adverse responses. Our goal is to determine whether a pharmacological intervention with methyl-donors (i.e., folic acid, Vitamins B6 \& B12, betaine, methionine, and choline) can avert this DNA methylation loss and mitigate the cardiovascular effects induced by PM exposure. The investigators will use experiments of human controlled exposure to PM - which reproduce conditions of exposure similar to those found in real life in urban environments - to conduct a double-blind, placebo-controlled crossover study. The investigators will test whether pharmacological intervention with methyl-donors attenuates the effects of PM exposure on DNA methylation (Aim 1), mRNA expression \& plasma cytokines (Aim 2), and blood pressure, arterial vasoconstriction, endothelial function, and autonomic control of the heart (Aim 3). The investigators' study is poised to be the first human investigation to translate a wealth of animal data showing that methyl-donors can be used to modulate epigenetic states and avert environmental effects. The investigators have a unique opportunity to achieve this goal because we have access to one of the few facilities worldwide for human controlled-exposure studies, as well as to state-of-the-art resources for epigenetics investigations. The investigators will examine DNA methylation and mRNA expression in T-helper cells from human individuals, a cell type with key roles in determining adverse hypertensive and endothelial responses, as shown in several animal models. The investigators will test the effects of methyl-donors on a battery of cardiovascular endpoints that are highly sensitive to PM exposure. The investigators will explore the use of advanced statistical methods for mediation analyses to understand the relationships among PM, DNA methylation, RNA expression, plasma cytokines, and cardiovascular endpoints. The study will be conducted by an investigative team that has conducted seminal work in all of the research areas on which this proposal is built upon, including environmental epigenetics, cardiovascular effects of PM, and human controlled exposure studies.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| methyl donor | Experimental | Drug: methyl donorMethyl donor is made up of: 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12 The design will include a 2 week placebo run-in followed by a baseline blank study (2-hrs exposure to medical air) to provide benchmarks for all assessed variables. Participants will then receive a 4-week placebo treatment before the first PM2.5 exposure study. A 4-week methyl-donor treatment (Dose: 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12 once a day) will precede the 2nd PM2.5 exposure. |
| placebo | Placebo comparator | Drug: Placeboplacebo: The design will include a 2 week placebo run-in followed by a baseline blank study (2-hrs exposure to medical air) to provide benchmarks for all assessed variables. Participants will then receive a 4-week placebo treatment before the first PM2.5 exposure study. A 4-week methyl-donor treatment (Dose: 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12 once a day) will precede the 2nd PM2.5 exposure. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Healthy volunteer
- Age 18-60 years old
- Non-smoker
- must be able to fast 8 hours prior to exposure visits and for a further 4 hours during the exposure
Key exclusion criteria (6 listed)
- Subjects must not be regularly taking multivitamins, vitamins C \& E, folate, medications, fish oil or aspirin, oral or inhaled steroids, for 4 weeks before and during the trial.
- Lipid abnormalities
- Asthma or respiratory disease
- Hypertension (Bp> 140/90) or taking any blood pressure drug
- Known cardiac disease
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 |
|---|---|---|
| methyl donorAlso: Vitamin B6, Vitamin B12, Folic Acid, PlaceboThe design will include a 2 week placebo run-in followed by a baseline blank study (2-hrs exposure to medical air) to provide benchmarks for all assessed variables. Participants will then receive a 4-week placebo treatment before the first PM2.5 exposure study. A 4-week methyl-donor treatment (Dose: 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12 once a day) will precede the 2nd PM2.5 exposure. | Drug | methyl donor |
| PlaceboPlacebo | Drug | placebo |
Primary outcome
DNA methylation in circulating T-helper lymphocytes of six candidate genes (TNFa, TGFb, IFNg, IL17, IL2, IL6)
Time frame: 2 years
Blood will be collected from venous phlebotomy and processed for Th-cell isolation within 4hrs. DNA extraction will be performed manually on fresh unfrozen cells. DNA methylation analyses will be conducted using bisulfite-polymerase chain reaction-pyrosequencing. To select target sequences within each gene, we will rely both on assays from previous investigations and bioinformatic analysis using information from the genome browser on transcription factor binding sites conserved in the human/mouse/rat alignment, histone marks associated with active regulatory sequences and gene accessibility, and nucleosome occupancy. We will validate all assays using a titration curve of 0%-100% methylated DNA. Batch effect will be controlled by: a) using 0%, 50%, 100% methylation and universal DNA in each plate; b) running all samples from the same volunteer in one plate. We will intersperse 5% blind duplicates to test reproducibility. All samples will be assayed in duplicate runs.
1 secondary outcome
Blood pressure (BP) , brachial artery diameter (BAD), endothelium-dependent flow-mediated dilation (ED-FMD) and heart rate variability (HRV).
Time frame: 2 years
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 11 May 2017.
- Background: PubMed 20458016Brook RD, Rajagopalan S, Pope CA 3rd, Brook JR, Bhatnagar A, Diez-Roux AV, Holguin F, Hong Y, Luepker RV, Mittleman MA, Peters A, Siscovick D, Smith SC Jr, Whitsel L, Kaufman JD; American Heart Association Council on Epidemiology and Prevention, Council on the Kidney in Cardiovascular Disease, and Council on Nutrition, Physical Activity and Metabolism. Particulate matter air pollution and cardiovascular disease: An update to the scientific statement from the American Heart Association. Circulation. 2010 Jun 1;121(21):2331-78. doi: 10.1161/CIR.0b013e3181dbece1. Epub 2010 May 10.
- Background: PubMed 19119685O'Toole TE, Conklin DJ, Bhatnagar A. Environmental risk factors for heart disease. Rev Environ Health. 2008 Jul-Sep;23(3):167-202. doi: 10.1515/reveh.2008.23.3.167.
- Background: PubMed 15466639Zanobetti A, Canner MJ, Stone PH, Schwartz J, Sher D, Eagan-Bengston E, Gates KA, Hartley LH, Suh H, Gold DR. Ambient pollution and blood pressure in cardiac rehabilitation patients. Circulation. 2004 Oct 12;110(15):2184-9. doi: 10.1161/01.CIR.0000143831.33243.D8. Epub 2004 Oct 4.
- Background: PubMed 20409976Brook RD, Rajagopalan S. Particulate matter, air pollution, and blood pressure. J Am Soc Hypertens. 2009 Sep-Oct;3(5):332-50. doi: 10.1016/j.jash.2009.08.005.
- Background: PubMed 20935292Brook RD, Bard RL, Burnett RT, Shin HH, Vette A, Croghan C, Phillips M, Rodes C, Thornburg J, Williams R. Differences in blood pressure and vascular responses associated with ambient fine particulate matter exposures measured at the personal versus community level. Occup Environ Med. 2011 Mar;68(3):224-30. doi: 10.1136/oem.2009.053991. Epub 2010 Oct 8.
- Background: PubMed 19701101Liu L, Ruddy T, Dalipaj M, Poon R, Szyszkowicz M, You H, Dales RE, Wheeler AJ. Effects of indoor, outdoor, and personal exposure to particulate air pollution on cardiovascular physiology and systemic mediators in seniors. J Occup Environ Med. 2009 Sep;51(9):1088-98. doi: 10.1097/JOM.0b013e3181b35144.
- Background: PubMed 15927967O'Neill MS, Veves A, Zanobetti A, Sarnat JA, Gold DR, Economides PA, Horton ES, Schwartz J. Diabetes enhances vulnerability to particulate air pollution-associated impairment in vascular reactivity and endothelial function. Circulation. 2005 Jun 7;111(22):2913-20. doi: 10.1161/CIRCULATIONAHA.104.517110. Epub 2005 May 31.
- Background: PubMed 18378616Baccarelli A, Cassano PA, Litonjua A, Park SK, Suh H, Sparrow D, Vokonas P, Schwartz J. Cardiac autonomic dysfunction: effects from particulate air pollution and protection by dietary methyl nutrients and metabolic polymorphisms. Circulation. 2008 Apr 8;117(14):1802-9. doi: 10.1161/CIRCULATIONAHA.107.726067. Epub 2008 Mar 31.
- Background: PubMed 17149139Adar SD, Gold DR, Coull BA, Schwartz J, Stone PH, Suh H. Focused exposures to airborne traffic particles and heart rate variability in the elderly. Epidemiology. 2007 Jan;18(1):95-103. doi: 10.1097/01.ede.0000249409.81050.46.
- Results publication: PubMed 28367952Zhong J, Trevisi L, Urch B, Lin X, Speck M, Coull BA, Liss G, Thompson A, Wu S, Wilson A, Koutrakis P, Silverman F, Gold DR, Baccarelli AA. B-vitamin Supplementation Mitigates Effects of Fine Particles on Cardiac Autonomic Dysfunction and Inflammation: A Pilot Human Intervention Trial. Sci Rep. 2017 Apr 3;7:45322. doi: 10.1038/srep45322.
- Results publication: PubMed 28289216Zhong J, Karlsson O, Wang G, Li J, Guo Y, Lin X, Zemplenyi M, Sanchez-Guerra M, Trevisi L, Urch B, Speck M, Liang L, Coull BA, Koutrakis P, Silverman F, Gold DR, Wu T, Baccarelli AA. B vitamins attenuate the epigenetic effects of ambient fine particles in a pilot human intervention trial. Proc Natl Acad Sci U S A. 2017 Mar 28;114(13):3503-3508. doi: 10.1073/pnas.1618545114. Epub 2017 Mar 13.
- Results publication: PubMed 26123683Zhong J, Urch B, Speck M, Coull BA, Koutrakis P, Thorne PS, Scott J, Liu L, Brook RD, Behbod B, Gibson H, Silverman F, Mittleman MA, Baccarelli AA, Gold DR. Endotoxin and beta-1,3-d-Glucan in Concentrated Ambient Particles Induce Rapid Increase in Blood Pressure in Controlled Human Exposures. Hypertension. 2015 Sep;66(3):509-16. doi: 10.1161/HYPERTENSIONAHA.115.05342. Epub 2015 Jun 29.
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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.
Andrea Baccarelli, MD PHD MPH principal investigator
HSPH
Frances Silverman, PHD study director
Unity Health Toronto
Diane R. Gold, MD study chair
HSPH
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing methyl donor in people with Heart Rate and Heart Rate Variability, run by Harvard School of Public Health (HSPH) at 1 site in Canada.
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 4 inclusion and 6 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 11 May 2017. 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 Canada. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
DNA methylation in circulating T-helper lymphocytes of six candidate genes (TNFa, TGFb, IFNg, IL17, IL2, IL6) (time frame: 2 years). 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 NCT01864824, which also lists 12 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 11 May 2017.