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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT00953667
First received: August 4, 2009
Last updated: February 23, 2016
Last verified: January 2016
  Purpose
The purpose of this study is to determine genetic factors that affect responses to niacin therapy and endotoxemia in healthy volunteers.

Condition Intervention
Healthy Volunteers
Drug: Immediate Release Niacin, Extended Release Niacin, Endotoxin

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: The Genetics of Evoked Responses to Niacin and Endotoxemia: The GENE Study

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 400
Study Start Date: June 2007
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Niacin and Endotoxin
All subjects are expected to have the same interventions- Niacin and Endotoxin.
Drug: 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).
Other Names:
  • Niacor
  • Niaspan

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.
  Eligibility

Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  1. Known clinically manifest atherosclerotic cardiovascular disease, including coronary disease, cerebrovascular disease, or peripheral vascular disease.
  2. History of diabetes mellitus.
  3. Fasting glucose > 126 mg/dL.
  4. History of a non-skin malignancy within the previous 5 years.
  5. Renal insufficiency as defined by creatinine > 1.5 mg/dl at Screening Visit.
  6. 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.
  7. 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.
  8. 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.
  9. Total white blood cell count less than or equal to 3.0 THO/uL.
  10. Hemoglobin below 11.0 g/dL.
  11. Any major active rheumatologic, pulmonary, or dermatologic disease or inflammatory condition or minor active infection.
  12. History of HIV positive.
  13. 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).
  14. Patients who have undergone any organ transplant.
  15. Individuals who currently use tobacco products or have done so in the previous 30 days.
  16. Treatment with aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors, steroids or any immunomodulatory therapy 2 weeks prior to the Screening Visit.
  17. Treatment with statins, fibrates or niacin 4 weeks prior to the Screening Visit.
  18. Current daily use of Vitamin C > 1000 mg, Beta carotene > 1000 IU, vitamin A > 5000 IU, vitamin E > 400 IU, and selenium > 200 mcg.
  19. Positive urine pregnancy at the Screening Visit.
  20. Participation in another clinical trial within the previous 6 weeks prior to the Screening Visit.
  21. Poorly controlled blood pressure (BP > 160/110) or on any anti-hypertensive medications.
  22. A diagnosis of metabolic syndrome using updated 2004 NCEP ATPIII criteria.
  23. A history of severe lactose intolerance (e.g., intolerance of any milk intake).
  24. Any medical condition or abnormal laboratory value that is judged clinically significant by an investigator.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00953667

Locations
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
Investigators
Principal Investigator: Muredach P Reilly, M.B., MSCE University of Pennsylvania
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT00953667     History of Changes
Other Study ID Numbers: 805670 
Study First Received: August 4, 2009
Results First Received: July 29, 2015
Last Updated: February 23, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Endotoxemia
Bacteremia
Sepsis
Infection
Toxemia
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Niacin
Niacinamide
Nicotinic Acids
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Vasodilator Agents
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 25, 2016