Biosynthesis of PGD2 in Vivo

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

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

Phase I: Subjects were assigned to either placebo or aspirin groups. They were given 5 days of 81 mg aspirin or placebo. On day 5, they were given a single dose of niacin (600 mg) administered 30 minutes after the last dose of aspirin or placebo. The same subjects came back for cross-over study and were assigned to a different group. There was a 2-week washout period between each treatment. Urine was collected sequentially for analysis

Phase II: The same study subjects come back for an open label one week study. They were given 5 days of taking 81 mg Aspirin, taken once daily, followed by a single dose of 600 mg Niacin on day 6. Urine was collected sequentially for analysis

Study Overview

• Status: Completed
• Conditions: Hyperlipidemia
• Intervention / Treatment: Drug: Placebo; Drug: Aspirin; Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo phase I; Subjects were given 5 days of placebo. On day 5, they were given a single dose of niacin (600 mg) administered 30 minutes after the last dose of placebo. Urine was collected sequentially for analysis. The same subjects came back for cross-over study and were assigned to Aspirin group. There was a 2-week washout period between each treatment.	Drug: Placebo; Drug: Niacin; Other Names: Niacin 600 mg
ACTIVE_COMPARATOR: Aspirin phase I; Subjects were given 5 days of 81 mg aspirin. On day 5, they were given a single dose of niacin (600 mg) administered 30 minutes after the last dose of aspirin or placebo. Urine was collected sequentially for analysis.	Drug: Aspirin; Other Names: Aspirin 81 mg; Drug: Niacin; Other Names: Niacin 600 mg
ACTIVE_COMPARATOR: Aspirin phase II; In phase II study, subjects were given 5 days of 81 mg aspirin. On day 6, they were given a single dose of niacin (600 mg) administered 24 hours after the last dose of aspirin. Urine was collected sequentially for analysis	Drug: Aspirin; Other Names: Aspirin 81 mg; Drug: Niacin; Other Names: Niacin 600 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change of Area Under Curve for the Urinary Prostaglandins Concentration Versus Time Curve (AUC) in Response to Aspirin or Placebo	Percentage change of area under the urinary prostaglandins concentration versus time curve (AUC) in response to niacin with or without pretreatment of aspirin was studied. This outcome measures whether aspirin instead of placebo will impact the subjects' response to niacin. The area was normalized by percentile.	-2-0, 0-2, 2-4, 4-6, 6-12 and 12-24 hours pre or post niacin

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Study Chair: Garret FitzGerald, MD, University of Pennsylvania

Publications and helpful links

General Publications

• Song WL, Stubbe J, Ricciotti E, Alamuddin N, Ibrahim S, Crichton I, Prempeh M, Lawson JA, Wilensky RL, Rasmussen LM, Pure E, FitzGerald GA. Niacin and biosynthesis of PGD(2)by platelet COX-1 in mice and humans. J Clin Invest. 2012 Apr;122(4):1459-68. doi: 10.1172/JCI59262. Epub 2012 Mar 12.

Helpful Links

• Niacin and biosynthesis of PGD2 by platelet COX-1 in mice and humans

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (ACTUAL): January 1, 2012
• Study Completion (ACTUAL): January 1, 2012

Study Registration Dates

• First Submitted: December 16, 2010
• First Submitted That Met QC Criteria: January 10, 2011
• First Posted (ESTIMATE): January 12, 2011

Study Record Updates

• Last Update Posted (ACTUAL): June 23, 2021
• Last Update Submitted That Met QC Criteria: June 21, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias; Hyperlipidemias; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Antimetabolites; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Vitamins; Vitamin B Complex; Aspirin; Nicotinic Acids; Niacinamide; Niacin
• Other Study ID Numbers: 806115 - FitzGerald, MD