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The Genetics of Evoked Responses to Niacin and Endotoxemia: The GENE Study (GENE)

Primary Purpose

Healthy Volunteers

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Immediate Release Niacin, Extended Release Niacin, Endotoxin

About this trial

This is an interventional basic science trial for Healthy Volunteers

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Men and non-pregnant/lactating women between the ages of 18 and 45.
Self reported African American or Caucasian racial-ethnic background.
Body Mass Index (BMI) of ≥ 18 and ≤ 30.
Participants who are able to give written informed consent and willing to comply with all study-related procedures.

Exclusion Criteria:

Known clinically manifest atherosclerotic cardiovascular disease, including coronary disease, cerebrovascular disease, or peripheral vascular disease.
History of diabetes mellitus.
Fasting glucose > 126 mg/dL.
History of a non-skin malignancy within the previous 5 years.
Renal insufficiency as defined by creatinine > 1.5 mg/dl at Screening Visit.
History of liver disease or abnormal liver function tests (LFTs) (AST, ALT, Alk. Phos., GGT > 1.5x upper limit of normal (ULN); bilirubin > 2x ULN) at Screening Visit.
Men who are unwilling to limit alcohol consumption to <14 alcoholic drinks per week or < 4 alcoholic drinks per occasion (AMA / NIAAA criteria for "at risk" usage levels) while participating in the study.
Women who are unwilling to limit alcohol consumption to < 7 alcoholic drinks per week or < 3 alcoholic drinks per occasion (AMA / NIAAA criteria for "at risk" usage levels) while participating in the study.
Total white blood cell count less than or equal to 3.0 THO/uL.
Hemoglobin below 11.0 g/dL.
Any major active rheumatologic, pulmonary, or dermatologic disease or inflammatory condition or minor active infection.
History of HIV positive.
First degree family history of premature cardiovascular disease event (father or brother if diagnosed at before 55 years of age; mother or sister if diagnosed before 65 years of age).
Patients who have undergone any organ transplant.
Individuals who currently use tobacco products or have done so in the previous 30 days.
Treatment with aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors, steroids or any immunomodulatory therapy 2 weeks prior to the Screening Visit.
Treatment with statins, fibrates or niacin 4 weeks prior to the Screening Visit.
Current daily use of Vitamin C > 1000 mg, Beta carotene > 1000 IU, vitamin A > 5000 IU, vitamin E > 400 IU, and selenium > 200 mcg.
Positive urine pregnancy at the Screening Visit.
Participation in another clinical trial within the previous 6 weeks prior to the Screening Visit.
Poorly controlled blood pressure (BP > 160/110) or on any anti-hypertensive medications.
A diagnosis of metabolic syndrome using updated 2004 NCEP ATPIII criteria.
A history of severe lactose intolerance (e.g., intolerance of any milk intake).
Any medical condition or abnormal laboratory value that is judged clinically significant by an investigator.

Sites / Locations

University of Pennsylvania

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Niacin and Endotoxin

Arm Description

All subjects are expected to have the same interventions- Niacin and Endotoxin.

Outcomes

Primary Outcome Measures

Baseline and Peak TNF-alpha Values as Categorized by Race and Gender

Secondary Outcome Measures

Baseline and Peak C-Reactive Protein (CRP) Values as Categorized by Race and Gender

Full Information

NCT ID

NCT00953667

First Posted

August 4, 2009

Last Updated

February 23, 2016

Sponsor

University of Pennsylvania

1. Study Identification

Unique Protocol Identification Number

NCT00953667

Brief Title

The Genetics of Evoked Responses to Niacin and Endotoxemia: The GENE Study

Acronym

GENE

Official Title

The Genetics of Evoked Responses to Niacin and Endotoxemia: The GENE Study

Study Type

Interventional

2. Study Status

Record Verification Date

January 2016

Overall Recruitment Status

Completed

Study Start Date

June 2007 (undefined)

Primary Completion Date

February 2011 (Actual)

Study Completion Date

February 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Pennsylvania

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to determine genetic factors that affect responses to niacin therapy and endotoxemia in healthy volunteers.

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Healthy Volunteers

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

400 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Niacin and Endotoxin

Arm Type

Experimental

Arm Description

All subjects are expected to have the same interventions- Niacin and Endotoxin.

Intervention Type

Drug

Intervention Name(s)

Immediate Release Niacin, Extended Release Niacin, Endotoxin

Other Intervention Name(s)

Niacor, Niaspan

Intervention Description

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).

Primary Outcome Measure Information:

Title

Baseline and Peak TNF-alpha Values as Categorized by Race and Gender

Time Frame

Baseline (-15 min, -5 min), and 1, 2, 4, 6, 12, 18, and 24 hours post LPS

Secondary Outcome Measure Information:

Title

Baseline and Peak C-Reactive Protein (CRP) Values as Categorized by Race and Gender

Time Frame

Baseline ( -15 min, -5 min), and 1, 2, 4, 6, 12, 18, and 24 hours post LPS

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Men and non-pregnant/lactating women between the ages of 18 and 45. Self reported African American or Caucasian racial-ethnic background. Body Mass Index (BMI) of ≥ 18 and ≤ 30. Participants who are able to give written informed consent and willing to comply with all study-related procedures. Exclusion Criteria: Known clinically manifest atherosclerotic cardiovascular disease, including coronary disease, cerebrovascular disease, or peripheral vascular disease. History of diabetes mellitus. Fasting glucose > 126 mg/dL. History of a non-skin malignancy within the previous 5 years. Renal insufficiency as defined by creatinine > 1.5 mg/dl at Screening Visit. History of liver disease or abnormal liver function tests (LFTs) (AST, ALT, Alk. Phos., GGT > 1.5x upper limit of normal (ULN); bilirubin > 2x ULN) at Screening Visit. Men who are unwilling to limit alcohol consumption to <14 alcoholic drinks per week or < 4 alcoholic drinks per occasion (AMA / NIAAA criteria for "at risk" usage levels) while participating in the study. Women who are unwilling to limit alcohol consumption to < 7 alcoholic drinks per week or < 3 alcoholic drinks per occasion (AMA / NIAAA criteria for "at risk" usage levels) while participating in the study. Total white blood cell count less than or equal to 3.0 THO/uL. Hemoglobin below 11.0 g/dL. Any major active rheumatologic, pulmonary, or dermatologic disease or inflammatory condition or minor active infection. History of HIV positive. First degree family history of premature cardiovascular disease event (father or brother if diagnosed at before 55 years of age; mother or sister if diagnosed before 65 years of age). Patients who have undergone any organ transplant. Individuals who currently use tobacco products or have done so in the previous 30 days. Treatment with aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors, steroids or any immunomodulatory therapy 2 weeks prior to the Screening Visit. Treatment with statins, fibrates or niacin 4 weeks prior to the Screening Visit. Current daily use of Vitamin C > 1000 mg, Beta carotene > 1000 IU, vitamin A > 5000 IU, vitamin E > 400 IU, and selenium > 200 mcg. Positive urine pregnancy at the Screening Visit. Participation in another clinical trial within the previous 6 weeks prior to the Screening Visit. Poorly controlled blood pressure (BP > 160/110) or on any anti-hypertensive medications. A diagnosis of metabolic syndrome using updated 2004 NCEP ATPIII criteria. A history of severe lactose intolerance (e.g., intolerance of any milk intake). Any medical condition or abnormal laboratory value that is judged clinically significant by an investigator.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Muredach P Reilly, M.B., MSCE

Organizational Affiliation

University of Pennsylvania

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

30571184

Citation

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.

Results Reference

derived

PubMed Identifier

25579865

Citation

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.

Results Reference

derived

PubMed Identifier

24875672

Citation

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.

Results Reference

derived

PubMed Identifier

24504737

Citation

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.

Results Reference

derived

PubMed Identifier

23497455

Citation

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.

Results Reference

derived

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The Genetics of Evoked Responses to Niacin and Endotoxemia: The GENE Study

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