Nucleophilic Defense Against PM Toxicity (NEAT Trial)

Study Overview
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Brief Summary
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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
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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.

Official Title
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Nucleophilic Defense Against PM Toxicity

Conditions
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Air Pollution Toxicity

Intervention / Treatment
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* Dietary Supplement: L-carnosine
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals between 22-65 years of age of either gender and all ethnicities, All genders and all ethnicities Residing in or near the Louisville metropolitan area Consumes some type of meat/fish at least once a month during the past 3 months Carnosine levels below the median level of the population Agrees to complete all study visits and follow study intervention regimen Will be living in the study area throughout the study period, with no more than 1 week away from the study area. Exclusion Criteria: Consumed any dietary supplement more than 3 times per week in the past 4 weeks (one month) Current / ongoing treatment for substance abuse Currently undergoing treatment or have conditions which may cause participant to be immunosuppressed 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.) Diseases Affecting Bone Marrow capacity Diagnosis of any active cancer Recent organ / kidney transplant or replacement (Active/Long-Term Medications) Type 1 Diabetes Mellitus Untreated thyroid disease Untreated anemia Current acute infections (Influenza, fever, etc.) HIV positive status Active/current Hepatitis HepA, HepB or HepC or in past 6 months Currently or planning to be Pregnant / lactating Prisoners / vulnerable populations Other medical conditions that compromise completion of study Unwilling to provide consent

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: placebo controlled, randomized, double-blind
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: intervention group<br>Each participant will be given a daily oral dose of 2 grams of carnosine for 12 weeks | Dietary Supplement: L-carnosine<br>* a naturally occurring di-peptide<br>|
| Placebo Comparator: placebo group<br>Each participant will be given a daily oral dose of 2 grams of placebo for 12 weeks | Other: placebo<br>* an identically appearing supplement<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| endothelial progenitor cells | circulating pro-angiogenic cells | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| arterial stiffness | index of arterial function | 3 months | 
| endothelial microparticles | index of endothelial damage | 3 months | 
| platelet monocyte aggregates | index of platelet activation | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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air pollution, oxidative stress, intervention