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| ID | Type | Description | Link |
|---|---|---|---|
| 5R01ES019217 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Environmental Health Sciences (NIEHS) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| intervention group | Active Comparator | Each participant will be given a daily oral dose of 2 grams of carnosine for 12 weeks |
|
| placebo group | Placebo Comparator | Each participant will be given a daily oral dose of 2 grams of placebo for 12 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| L-carnosine | Dietary Supplement | a naturally occurring di-peptide |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Endothelial Progenitor Cells | circulating pro-angiogenic cells | 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| Augmentation Index | index of arterial function | 3 months |
| Endothelial Microparticles | index of endothelial damage | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Timothy E. O'Toole | University of Louisville | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Trials Unit | Louisville | Kentucky | 40202 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20595651 | Background | 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. | |
| 23559625 | Result | 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. |
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Only screened participants with the lowest levels of endogenous carnosine (n=299) were invited to participate in the full study.
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| ID | Title | Description |
|---|---|---|
| FG000 | L-carnosine | Each participant will be given a daily oral dose of 2 grams of carnosine for 12 weeks L-carnosine: a naturally occurring di-peptide |
| FG001 | Placebo Group | Each participant will be given a daily oral dose of 2 grams of placebo for 12 weeks placebo: an identically appearing supplement |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | L-carnosine Group | Each participant will be given a daily oral dose of 2 grams of carnosine for 12 weeks L-carnosine: a naturally occurring di-peptide |
| BG001 | Placebo Group | Each participant will be given a daily oral dose of 2 grams of placebo for 12 weeks placebo: an identically appearing supplement |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Endothelial Progenitor Cells | circulating pro-angiogenic cells | For some participants in both groups, insufficient blood samples were collected or there were errors in processing and data collection. Thus, the n=130 for both groups does not match with number of participants in the study visit. | Posted | Mean | Standard Error | # cells per CD41 minus cells | 3 months |
|
a total of 5 months, from initial screening until one month after study completion
adverse events as per clinical trials definition
Information on events collected from participant report and by clinical team
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | L-carnosine Group | Each participant will be given a daily oral dose of 2 grams of carnosine for 12 weeks L-carnosine: a naturally occurring di-peptide |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| diarhhea | Gastrointestinal disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| tingling sensation | Nervous system disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Timothy O'Toole Associate Professor | University of Louisville | 15024190808 | tim.otoole@louisville.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 14, 2020 | Aug 20, 2023 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D002336 | Carnosine |
| ID | Term |
|---|---|
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D004151 | Dipeptides |
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placebo controlled, randomized, double-blind
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double blind (participant, investigator)
| placebo |
| Other |
an identically appearing supplement |
|
| Platelet Monocyte Aggregates | percentage of CD14 events that are co-stained with CD41 (platelet glycoprotein GPIIb); also levels of CD62P (P-selectin) expression | 3 months |
| 27780829 | Result | 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. |
| 39215872 | Derived | Baba SP, Amraotkar AR, Hoetker D, Gao H, Gomes D, Zhao J, Wempe MF, Rice PJ, DeFilippis AP, Rai SN, Pope CA 3rd, Bhatnagar A, O'Toole TE. Evaluation of supplementary carnosine accumulation and distribution: an initial analysis of participants in the Nucleophilic Defense Against PM Toxicity (NEAT) clinical trial. Amino Acids. 2024 Aug 31;56(1):55. doi: 10.1007/s00726-024-03414-5. |
| 33372072 | Derived | 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. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| urinary carnosine levels | Mean | Standard Deviation | nmol/mg creatinine |
|
|
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| Secondary | Augmentation Index | index of arterial function | For some participants, this data could not be collected, so the n does not equal the total number of participants. | Posted | Mean | Standard Deviation | percentage of pulse pressure | 3 months |
|
|
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| Secondary | Endothelial Microparticles | index of endothelial damage | Posted | Mean | Standard Error | microparticles per microliter | 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. |
|
|
|
| Secondary | Platelet Monocyte Aggregates | percentage of CD14 events that are co-stained with CD41 (platelet glycoprotein GPIIb); also levels of CD62P (P-selectin) expression | For some participants, blood samples were not collected or there were errors in processing or data collection. Thus n=132 and 128 is less than total number of participants. | Posted | Mean | Standard Error | percent of events | 3 months |
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| 0 |
| 153 |
| 3 |
| 153 |
| 24 |
| 153 |
| EG001 | Placebo Group | Each participant will be given a daily oral dose of 2 grams of placebo for 12 weeks placebo: an identically appearing supplement | 0 | 146 | 3 | 146 | 16 | 146 |
| yeast infection | Infections and infestations | Non-systematic Assessment |
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| anxiety/depression | Psychiatric disorders | Non-systematic Assessment |
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| hypotension | Cardiac disorders | Systematic Assessment |
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| nausea | Gastrointestinal disorders | Non-systematic Assessment |
|
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| D009842 |
| Oligopeptides |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |