Biosynthesis of PGD2 in Vivo (Niacin)

We would like to see if aspirin could block niacin-induced flushing by analyzing blood and urine after taking aspirin.

Phase I: 5 days of 81 mg aspirin/placebo followed by 600 mg Niacin, 2 week washout and 5 days taking the alternate. The order in which this is given will be randomized or assigned by chance.

Phase II: One study week consisting of 5 days of taking 81 mg Aspirin, taken once daily, followed by a single dose of 600 mg Niacin on day 6.

Phase III: 5 days taking 81 mg Aspirin/placebo, 10 day washout in between.

Phase IV: Use of extended release niacin instead of instant release.

Phase V: A Celebrex study is necessary to explore the contribution of Cox-2 to niacin induced flushing.

The purpose of this study is to look at the roles of various blood cells and their contributions of different prostaglandins. The intention is that by better understanding these prostaglandins and various metabolites, it will provide insights into their roles in the cardiovascular system.

Prostaglandins and metabolites are naturally occurring substances found in the blood and urine which can act as markers which can be quantified and studied as we will be doing in this study. Flushing response to niacin will also be assessed by laser doppler measuring blood flow of the facial skin.

Untransformed and transformed data will be subjected to exploratory analysis of variance appropriated for a three factor design with one two period crossover factor and two non-repeated factors. Additionally, volunteer's test(s) for paired observations will characterize the magnitude of the niacin effect on the response variables within selected time points.

• Dietary Supplement: 5 days of placebo followed by 600mg niacin
  600 mg niacin
  Other Name: Niaspan
• Dietary Supplement: aspirin first
  5 days taking 81 mg Aspirin followed by a single dose of 600 mg Niacin
  Other Names:

  • baby aspirin
  • niaspan
• Drug: 81 mg Aspirin
  5 days taking 81 mg Aspirin
  Other Names:

  • low dose aspirin
  • baby aspirin
• Dietary Supplement: Niaspan
  dosage
  Other Name: niacin
• Drug: Celebrex and niacin
  Data will be handled exactly like phase 1.
  Other Name: niacin

• Placebo Comparator: Phase I, Period B
  Period B: 5 days of placebo, followed by a single dose of 600mg niacin.
  Intervention: Dietary Supplement: 5 days of placebo followed by 600mg niacin
• Placebo Comparator: sugar pill
  Intervention: Dietary Supplement: aspirin first
• Placebo Comparator: low dose aspirin or placebo
  5 days taking either 81 mg aspirin/placebo with at least 10 day washout in between.
  Intervention: Drug: 81 mg Aspirin
• Active Comparator: Single dose 2 gms Niaspan for 8 days
  Intervention: Dietary Supplement: Niaspan
• Placebo Comparator: Celebrex / Placebo
  Celebrex 200 mg/Placebo taken for 5 days, two times daily, followed by single dose of 600 mg niacin on day five. At least 10 days in between each dosing period.
  Intervention: Drug: Celebrex and niacin

Inclusion Criteria:

age between 18-70

• subject must be in good health as based on medical history
• All subjects must be non-smoking, non-pregnant volunteers
• Female subjects of child bearing potential must be using a medically acceptable method of contraception throughout the entire study period. All female subjects must consent to a urine pregnancy test at screening and just prior to the start of each treatment period of the study, which must be negative at all time points.

Exclusion Criteria:

• subjects with any medical condition that according to the investigator may interfere with interpretation of the study results, be indicative of an underlying disease state, or compromise the safety of a potential subject.
• subjects who have received an experimental drug within 30 days prior to the study.
• subjects who have taken medications at least 10 days prior to the study. Birth Control pills are acceptable and shall not be excluded.
• Subjects who have taken aspirin or aspirin containing products for at least 10 days prior to the study.
• Subjects who have taken acetaminophen, NSAIDS, COX-2 inhibitors (OTC or prescription) for at least 10 days prior to the study.
• Subjects who are currently consuming any type of tobacco product(s).
• Subjects who consume high doses of antioxidant vitamins daily (vitamin C > 1000mg, Vitamin E > 400 IU, Beta Carotene > 1000IU, Vitamin A > 5000IU, Selenium > 200mcg, Folic Acid > 1mg) for the 2 weeks prior to the start of the study and throughout the study.
• Subjects who consume alcohol, caffeine or high fat food 24 hours prior to study.