Clinical trial NCT03314987: Nucleophilic Defense Against PM Toxicity (NEAT Trial)
Official title: Nucleophilic Defense Against PM Toxicity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Air Pollution Toxicity
Keywords: air pollution
oxidative stress
intervention
Lead sponsor: University of Louisville
Sponsor class: OTHER
Collaborators: name: National Institute of Environmental Health Sciences (NIEHS)
First posted: 2017-10-19
Enrollment: 299
Sex: ALL
Minimum age (years): 22
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: placebo controlled, randomized, double-blind
Primary purpose: BASIC_SCIENCE

Brief summary: Carnosine is a naturally occurring peptide found in high levels in skeletal muscle and the brain and is also available commercially as a dietary supplement. Since carnosine has anti-oxidant properties and air pollution exposure induces a state of oxidative stress, the purpose of this study is to see if those taking carnosine as a dietary supplement are protected from air pollution-induced oxidative stress and adverse cardiovascular outcomes.

Detailed description: This is a placebo controlled, randomized, double-blind, interventional trial investigating the efficacy of carnosine in reducing the effects of particulate matter air pollution (PM2.5). A total of 240 participants from the Louisville metropolitan and neighboring areas will be randomized into two dietary supplement study groups - carnosine (n=120) versus placebo (n=120). Intervention of study dietary supplements will occur from May through September, when the levels of PM2.5.are highest in the Louisville, KY area. Study participants will be given a daily oral dose of total of 2 grams of carnosine (or placebo) for a total of 12 consecutive weeks (during May through September).

Urinary levels of carnosine will be used to screen and identify potential candidates with low carnosine levels. Those with levels less than the median levels of the population, will be invited to participate in the study. The following measurements will be performed - blood and urine sample collection, physical examination, arterial stiffness, physical function, and self-reported surveys on environmental exposure, sleep, diet, and exercise. Supplement intervention (carnosine or placebo) will be initiated at the time of Baseline Assessment and will continue for 12 weeks from that date. Two follow up visits will occur at 6 weeks and 12 weeks respectively after initiating supplementation.

This innovative clinical investigation will provide an insight into the pre and post intervention effects of a cheap, safe, and over-the-counter available dietary supplement in countering the effects of air pollution.

Eligibility criteria: Inclusion Criteria:

1. Individuals between 22-65 years of age of either gender and all ethnicities,
2. All genders and all ethnicities
3. Residing in or near the Louisville metropolitan area
4. Consumes some type of meat/fish at least once a month during the past 3 months
5. Carnosine levels below the median level of the population
6. Agrees to complete all study visits and follow study intervention regimen
7. Will be living in the study area throughout the study period, with no more than 1 week away from the study area.

Exclusion Criteria:

1. Consumed any dietary supplement more than 3 times per week in the past 4 weeks (one month)
2. Current / ongoing treatment for substance abuse
3. Currently undergoing treatment or have conditions which may cause participant to be immunosuppressed
4. Diseases Affecting Peripheral Cell Count (i.e. Autoimmune Diseases - Hashimoto, Rheumatoid Arthritis, SLE, Rheumatoid Arthritis, Sjogren syndrome, Ankylosing Spondylitis, Takayasu arteritis, Kawasaki disease, Polyarteritis nodosa.)
5. Diseases Affecting Bone Marrow capacity
6. Diagnosis of any active cancer
7. Recent organ / kidney transplant or replacement (Active/Long-Term Medications)
8. Type 1 Diabetes Mellitus
9. Untreated thyroid disease
10. Untreated anemia
11. Current acute infections (Influenza, fever, etc.)
12. HIV positive status
13. Active/current Hepatitis HepA, HepB or HepC or in past 6 months
14. Currently or planning to be Pregnant / lactating
15. Prisoners / vulnerable populations
16. Other medical conditions that compromise completion of study
17. Unwilling to provide consent

Primary outcomes:
measure: Endothelial Progenitor Cells
timeFrame: 3 months
Secondary outcomes:
measure: Augmentation Index
timeFrame: 3 months
measure: Endothelial Microparticles
timeFrame: Samples were collected from each participant at baseline, after ~6wk of intervention, and after ~12wk of intervention. Measurement will be performed on archived samples once assay is in place.
measure: Platelet Monocyte Aggregates
timeFrame: 3 months
Other outcomes:
Locations:
city: Louisville
country: United States
facility: Clinical Trials Unit
state: Kentucky
Study officials:
affiliation: University of Louisville
name: Timothy E. O'Toole
role: PRINCIPAL_INVESTIGATOR
References:
citation: O'Toole TE, Hellmann J, Wheat L, Haberzettl P, Lee J, Conklin DJ, Bhatnagar A, Pope CA 3rd. Episodic exposure to fine particulate air pollution decreases circulating levels of endothelial progenitor cells. Circ Res. 2010 Jul 23;107(2):200-3. doi: 10.1161/CIRCRESAHA.110.222679. Epub 2010 Jul 1.
citation: Barski OA, Xie Z, Baba SP, Sithu SD, Agarwal A, Cai J, Bhatnagar A, Srivastava S. Dietary carnosine prevents early atherosclerotic lesion formation in apolipoprotein E-null mice. Arterioscler Thromb Vasc Biol. 2013 Jun;33(6):1162-70. doi: 10.1161/ATVBAHA.112.300572. Epub 2013 Apr 4.
citation: Pope CA 3rd, Bhatnagar A, McCracken JP, Abplanalp W, Conklin DJ, O'Toole T. Exposure to Fine Particulate Air Pollution Is Associated With Endothelial Injury and Systemic Inflammation. Circ Res. 2016 Nov 11;119(11):1204-1214. doi: 10.1161/CIRCRESAHA.116.309279. Epub 2016 Oct 25.
citation: O'Toole TE, Amraotkar AA, DeFilippis AP, Rai SN, Keith RJ, Baba SP, Lorkiewicz P, Crandell CE, Pariser GL, Wingard CJ, Pope Iii CA, Bhatnagar A. 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. BMJ Open. 2020 Dec 28;10(12):e039118. doi: 10.1136/bmjopen-2020-039118.