- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00953667
The Genetics of Evoked Responses to Niacin and Endotoxemia: The GENE Study (GENE)
February 23, 2016 updated by: University of Pennsylvania
The purpose of this study is to determine genetic factors that affect responses to niacin therapy and endotoxemia in healthy volunteers.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
400
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States, 19104
- University of Pennsylvania
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 45 years (Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Niacin and Endotoxin
All subjects are expected to have the same interventions- Niacin and 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).
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
Baseline (-15 min, -5 min), and 1, 2, 4, 6, 12, 18, and 24 hours post LPS
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
Baseline ( -15 min, -5 min), and 1, 2, 4, 6, 12, 18, and 24 hours post LPS
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Muredach P Reilly, M.B., MSCE, University of Pennsylvania
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
June 1, 2007
Primary Completion (Actual)
February 1, 2011
Study Completion (Actual)
February 1, 2011
Study Registration Dates
First Submitted
August 4, 2009
First Submitted That Met QC Criteria
August 5, 2009
First Posted (Estimate)
August 6, 2009
Study Record Updates
Last Update Posted (Estimate)
March 24, 2016
Last Update Submitted That Met QC Criteria
February 23, 2016
Last Verified
January 1, 2016
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Infections
- Systemic Inflammatory Response Syndrome
- Inflammation
- Sepsis
- Bacteremia
- Toxemia
- Endotoxemia
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Vasodilator Agents
- Antimetabolites
- Micronutrients
- Hypolipidemic Agents
- Lipid Regulating Agents
- Vitamins
- Vitamin B Complex
- Niacin
Other Study ID Numbers
- 805670
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Healthy Volunteers
-
AstraZenecaCompletedHealthy Elderly Volunteers | Healthy Young VolunteersUnited States
-
Syndax PharmaceuticalsCompletedHealthy Volunteers | Volunteers | Normal Volunteers | Human VolunteersUnited States
-
Syndax PharmaceuticalsCompletedHealthy Volunteers | Volunteers | Normal Volunteers | Human VolunteersUnited States
-
University Hospital, Clermont-FerrandUnite de Nutrition Humaine UMR 1019- INRAE; Unite MetaGenoPolis INRAE; France...CompletedHealthy Volunteers | Frail VolunteersFrance
-
Galera Therapeutics, Inc.CelerionCompletedHealthy | Healthy VolunteersUnited States
-
Newcastle UniversityCompletedGI Glycaemic Index Healthy Volunteers | GL Glycaemic Load Healthy VolunteersUnited Kingdom
-
Galera Therapeutics, Inc.Syneos HealthCompleted
-
Galera Therapeutics, Inc.Syneos HealthCompletedHealthy | Healthy VolunteersAustralia
-
Maastricht University Medical CenterCompletedHealthy Volunteers | Healthy Subjects | Healthy AdultsNetherlands
-
PMV Pharmaceuticals, IncRecruitingHealthy VolunteersUnited States
Clinical Trials on Immediate Release Niacin, Extended Release Niacin, Endotoxin
-
National Heart, Lung, and Blood Institute (NHLBI)CompletedCardiovascular DiseaseUnited States
-
Hangzhou Highlightll Pharmaceutical Co., LtdCompleted
-
AstraZenecaWithdrawnHealthy Male Subjects | Pharmacokinetics | Safety | Food EffectUnited Kingdom
-
University of LeipzigCompletedCoronary Disease | HypolipoproteinemiaGermany
-
University of HawaiiUnited States Department of DefenseCompletedHIV Infections | Dyslipidemia | Endothelial DysfunctionUnited States
-
George ThanassoulisJewish General Hospital; Laval University; Quebec Heart InstituteWithdrawnAortic Stenosis and Lipoprotein(a) LevelsCanada
-
North Texas Veterans Healthcare SystemNational Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health...CompletedAortocoronary Saphenous Vein Bypass Graft Atherosclerosis | Intermediate Saphenous Vein Graft LesionsUnited States
-
Cortria CorporationPPD; Pharmena North AmericaCompleted
-
University of MiamiTerminatedDiabetes Mellitus, Type 2 | Kidney Failure, Chronic | HyperlipidemiaUnited States
-
ApoPharmaCompleted