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The purpose of this study is to determine genetic factors that affect responses to niacin therapy and endotoxemia in healthy volunteers.
Niacin is a vitamin that has beneficial effects on cholesterol (a type of fat in the blood) when used in high doses. Different people respond differently to cholesterol lowering doses of niacin, some people have a side effect termed flushing (similar to a hot flash) while others do not and some people have more pronounced effects on cholesterol. Endotoxin or lipopolysaccharide (LPS) is a small part of bacteria (that is no longer living) that can cause many of the effects similar to bacterial infections in humans. However, it can be administered in very small amounts to produce a mild inflammatory response much the same as a 'flu-like" illness. Within 1 ½ -3 hours after giving LPS by vein, a response consisting of fever, chills, headache, nausea and vomiting and generalized aches and pains will occur which lasts up to 6-8 hours. In addition to the flu like symptoms, the inflammation causes changes in cholesterol, triglycerides and glucose clearance. Different people respond differently to endotoxin and inflammation. We are performing this study to see if there are genetic factors that predict how people will respond to niacin and to endotoxin and its inflammatory response.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Niacin and Endotoxin | Experimental | All subjects are expected to have the same interventions- Niacin and Endotoxin. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Immediate Release Niacin, Extended Release Niacin, Endotoxin | Drug | Subjects receive a one-time 1000mg dose of immediate release Niacin (Niacor pills), a one-time 1000mg dose of extended release Niacin (Niaspan pill) and one-time 1ng/kg injection of endotoxin (LPS). |
| Measure | Description | Time Frame |
|---|---|---|
| Baseline and Peak TNF-alpha Values as Categorized by Race and Gender | Baseline (-15 min, -5 min), and 1, 2, 4, 6, 12, 18, and 24 hours post LPS |
| Measure | Description | Time Frame |
|---|---|---|
| Baseline and Peak C-Reactive Protein (CRP) Values as Categorized by Race and Gender | Baseline ( -15 min, -5 min), and 1, 2, 4, 6, 12, 18, and 24 hours post LPS |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Muredach P Reilly, M.B., MSCE | University of Pennsylvania | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30571184 | Derived | Ferguson JF, Xue C, Gao Y, Tian T, Shi J, Zhang X, Wang Y, Li YD, Wei Z, Li M, Zhang H, Reilly MP. Tissue-Specific Differential Expression of Novel Genes and Long Intergenic Noncoding RNAs in Humans With Extreme Response to Evoked Endotoxemia. Circ Genom Precis Med. 2018 Nov;11(11):e001907. doi: 10.1161/CIRCGEN.117.001907. | |
| 25579865 |
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All subjects received niacin and LPS doses. There were no separate arms.
400 subjects were enrolled over an approximate 3.5 year period in order to reach target of about 300 subjects completing all visits. Study ended with 277 subjects completing all visits.
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| ID | Title | Description |
|---|---|---|
| FG000 | Niacin and Endotoxin | Immediate Release Niacin, Extended Release Niacin, Endotoxin: Subjects receive a one-time 1000mg dose of immediate release Niacin (Niacor pills), a one-time 1000mg dose of extended release Niacin (Niaspan pill) and one-time 1ng/kg injection of endotoxin (LPS). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Niacin and Endotoxin | Immediate Release Niacin, Extended Release Niacin, Endotoxin: Subjects receive a one-time 1000mg dose of immediate release Niacin (Niacor pills), a one-time 1000mg dose of extended release Niacin (Niaspan pill) and one-time 1ng/kg injection of endotoxin (LPS). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Baseline and Peak TNF-alpha Values as Categorized by Race and Gender | This analysis population was categorized by race and gender as follows: European American (EA) male n=102, African American (AA) male n=41, EU female n=91, and AA female n=60. Results include measurements at baseline and peak levels of Tumor Necrosis Factor- alpha (TNF-alpha). | Posted | Median | Inter-Quartile Range | pg/ml | Baseline (-15 min, -5 min), and 1, 2, 4, 6, 12, 18, and 24 hours post LPS |
|
AE data collected for approximately 3.5 years, during the course of all study visits
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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 | Niacin and Endotoxin | Immediate Release Niacin, Extended Release Niacin, Endotoxin: Subjects receive a one-time 1000mg dose of immediate release Niacin (Niacor pills), a one-time 1000mg dose of extended release Niacin (Niaspan pill) and one-time 1ng/kg injection of endotoxin (LPS). |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Muredach Reilly | UPenn | 215-573-1214 | muredach@mail.med.upenn.edu |
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| ID | Term |
|---|---|
| D004731 | Endotoxins |
| D009525 | Niacin |
| ID | Term |
|---|---|
| D001427 | Bacterial Toxins |
| D014118 | Toxins, Biological |
| D001685 | Biological Factors |
| D009539 | Nicotinic Acids |
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|
| Ferguson JF, Shah RY, Shah R, Mehta NN, Rickels MR, Reilly MP. Activation of innate immunity modulates insulin sensitivity, glucose effectiveness and pancreatic beta-cell function in both African ancestry and European ancestry healthy humans. Metabolism. 2015 Apr;64(4):513-520. doi: 10.1016/j.metabol.2014.12.007. Epub 2014 Dec 26. |
| 24875672 | Derived | Ferguson JF, Ryan MF, Gibney ER, Brennan L, Roche HM, Reilly MP. Dietary isoflavone intake is associated with evoked responses to inflammatory cardiometabolic stimuli and improved glucose homeostasis in healthy volunteers. Nutr Metab Cardiovasc Dis. 2014 Sep;24(9):996-1003. doi: 10.1016/j.numecd.2014.03.010. Epub 2014 Apr 18. |
| 24504737 | Derived | Liu Y, Ferguson JF, Xue C, Ballantyne RL, Silverman IM, Gosai SJ, Serfecz J, Morley MP, Gregory BD, Li M, Reilly MP. Tissue-specific RNA-Seq in human evoked inflammation identifies blood and adipose LincRNA signatures of cardiometabolic diseases. Arterioscler Thromb Vasc Biol. 2014 Apr;34(4):902-12. doi: 10.1161/ATVBAHA.113.303123. Epub 2014 Feb 6. |
| 23497455 | Derived | Ferguson JF, Patel PN, Shah RY, Mulvey CK, Gadi R, Nijjar PS, Usman HM, Mehta NN, Shah R, Master SR, Propert KJ, Reilly MP. Race and gender variation in response to evoked inflammation. J Transl Med. 2013 Mar 12;11:63. doi: 10.1186/1479-5876-11-63. |
| Adverse Event |
|
| poor venous access,unable to draw blood |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
| Secondary | Baseline and Peak C-Reactive Protein (CRP) Values as Categorized by Race and Gender | This analysis population was categorized by race and gender as follows: European American (EA) male n=102, African American (AA) male n=41, EU female n=91, and AA female n=60. Results include measurements at baseline and peak levels of C-Reactive Protein (CRP). | Posted | Median | Inter-Quartile Range | mg/L | Baseline ( -15 min, -5 min), and 1, 2, 4, 6, 12, 18, and 24 hours post LPS |
|
|
|
| 0 |
| 400 |
| 86 |
| 400 |
| Vomitting | Gastrointestinal disorders | Non-systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
|
| >2g drop in Hgb or <10 g/dL | Blood and lymphatic system disorders | Non-systematic Assessment | > 2g drop in Hgb from baseline or <10 g/dL Hgb at discharge |
|
| Lightheadedness | Cardiac disorders | Non-systematic Assessment | subject reported lightheadedness or dizziness |
|
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| D000147 |
| Acids, Heterocyclic |
| D006571 | Heterocyclic Compounds |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
|
| Peak CRP in AA males |
|
| Baseline CRP in EA females |
|
| Peak CRP in EA females |
|
| Baseline CRP in AA females |
|
| Peak CRP in AA females |
|