Biosynthesis of PGD2 in Vivo

Condition(s) targeted: Healthy Volunteer

Intervention: 5 days of placebo followed by 600mg niacin (Dietary Supplement); aspirin first (Dietary Supplement); 81 mg Aspirin (Drug); Niaspan (Dietary Supplement); Celebrex and niacin (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: University of Pennsylvania

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.

Official title: A Pilot Study to Measure Plasma and Urinary Prostaglandin D2 Metabolites Evoked by Niacin

Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Primary outcome: Area under the urinary prostaglandins concentration versus time curve (AUC) in response to niacin and aspirin

Secondary outcome: Area under the flushing response versus time curve (AUC) in response to niacin

Detailed description: 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.

Minimum age: 18 Years. Maximum age: 70 Years. Gender(s): Both.

Criteria:

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.

University of Pennsylvania Hospital, Phila., Pennsylvania 19104, United States

Starting date: July 2007
Last updated: May 14, 2013