Article Text

Download PDFPDF

Protocol
Protocol to assess the efficacy of carnosine supplementation in mitigating the adverse cardiovascular responses to particulate matter (PM) exposure: the Nucleophilic Defense Against PM Toxicity (NEAT) trial
  1. Timothy E. O'Toole1,
  2. Alok A. Amraotkar1,2,
  3. Andrew P. DeFilippis3,
  4. Shesh N. Rai4,
  5. Rachel J. Keith1,
  6. Shahid P. Baba1,
  7. Pawel Lorkiewicz1,5,
  8. Catherine E. Crandell6,
  9. Gina L. Pariser6,
  10. Christopher J. Wingard6,
  11. C. Arden Pope III7,
  12. Aruni Bhatnagar1
  1. 1Division of Environmental Medicine, Christina Lee Brown Envirome Institute, University of Louisville, Louisville, Kentucky, USA
  2. 2Division of Cardiovascular Medicine, University of Louisville, Louisville, Kentucky, USA
  3. 3Department of Medicine, Vanderbilt University, Nashville, TN, USA
  4. 4Department of Biostatistics and Bioinfomatics, University of Louisville, Louisville, Kentucky, USA
  5. 5Department of Chemistry, University of Louisville, Louisville, KY, USA
  6. 6Department of Physical Therapy, Bellarmine University, Louisville, Kentucky, USA
  7. 7Department of Economics, Brigham Young University, Provo, Utah, USA
  1. Correspondence to Dr Timothy E. O'Toole; teotoo01{at}louisville.edu

Abstract

Introduction Exposure to airborne particulate matter (PM) is associated with cardiovascular disease. These outcomes are believed to originate from pulmonary oxidative stress and the systemic delivery of oxidised biomolecules (eg, aldehydes) generated in the lungs. Carnosine is an endogenous di-peptide (β-alanine-L-histidine) which promotes physiological homeostasis in part by conjugating to and neutralising toxic aldehydes. We hypothesise that an increase of endogenous carnosine by dietary supplementation would mitigate the adverse cardiovascular outcomes associated with PM exposure in humans.

Methods and analysis To test this, we designed the Nucleophilic Defense Against PM Toxicity trial. This trial will enroll 240 participants over 2 years and determine if carnosine supplementation mitigates the adverse effects of PM inhalation. The participants will have low levels of endogenous carnosine to facilitate identification of supplementation-specific outcomes. At enrollment, we will measure several indices of inflammation, preclinical cardiovascular disease and physical function. Participants will be randomly allocated to carnosine or placebo groups and instructed to take their oral supplement for 12 weeks with two return clinical visits and repeated assessments during times of peak PM exposure (June–September) in Louisville, Kentucky, USA. Statistical modelling approaches will be used to assess the efficacy of carnosine supplementation in mitigating adverse outcomes.

Ethics and dissemination This study protocol has been approved by the Institutional Review Board at the University of Louisville. Results from this study will be disseminated at scientific conferences and in peer-reviewed publications.

Trial registration: NCT03314987; Pre-results

  • vascular medicine
  • cardiology
  • clinical trials
  • toxicology
  • cardiology
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

Statistics from Altmetric.com

Footnotes

  • Contributors TEO: study design, study funding, endpoint measurements, manuscript preparation; AAA: study design, recruitment, study visits, vascular function, manuscript preparation; APD: study design, clinical oversight; SNR: study design, statistical analysis: RJK: study design, recruitment, study visits, vascular function; SPB: study design; PL: endpoint measurements; CEC: study design, endpoint measurements; GLP: study design, endpoint measurements; CJW: study design, endpoint measurements; CAP: study design, study funding, statistical analysis, manuscript preparation; AB: study design, study funding, manuscript preparation.

  • Funding This work is supported by a grant from the National Institutes of Health (RO1ES019217).

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Patient consent for publication Not required.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.