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

Healthy Volunteers Clinical Trial

— GENE  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00953667
• Other study ID #: 805670
• Status: Active, not recruiting
• Phase: N/A
• First received: August 4, 2009
• Last updated: February 17, 2011
• Start date: June 2007
• Est. completion date: September 2010

Study information

• Verified date: February 2011
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 400
• Est. completion date: September 2010
• Est. primary completion date: September 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

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. 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 LFTs (AST, ALT, Alk. Phos., GGT > 1.5x 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, 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.

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Endotoxemia
• Healthy Volunteers

Intervention

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).

Locations

Country	Name	City	State
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Candidate gene variation will influence (1) the metabolic response to acute niacin administration and (2) the vascular injury response during endotoxemia.		approximately 5 years	No