Enrolling by Invitation

NCT Number: NCT04464070

Pathways of Eicosanoid Metabolism

Prostaglandins are important signaling compounds formed from arachidonic acid. The enzymes that form prostaglandins, cyclooxygenase-1 and -2 are the targets of non-steroidal anti-inflammatory drugs (NSAIDs). Because prostaglandins are very unstable in the body, they can not be measured directly. Instead, their metabolites are isolated from urine or blood and quantified as markers of formation of the parent, active compounds.

The investigators are testing the hypothesis that there is a previously unrecognized metabolic pathway between two prostaglandins. The investigators hypothesize that prostaglandin D2 (PGD2), in addition to its known metabolism to PGD-M, is also metabolized to 11-dehydro-thromboxane B2 (11-dehydro-TxB2).

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Key information

Conditions

Metabolism of Prostaglandin D2

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Early Phase 1

Primary location

Vanderbilt University

Nashville, Tennessee, 37232, United States

About this study

The objective of this study is to determine whether PGD2 is metabolized to 11-dehydro-TxB2 in humans. Because the levels of PGD2 and its metabolite, PGD-M, are low in human urine, the investigators will use the model of niacin-induced flushing which is associated with a increased release of PGD2 from skin cells. It has been demonstrated that increased formation of PGD2 is associated with increased levels of urinary 11-dehydro-TxB2 in patients with mastocytosis.

In order to test whether niacin-induced biosynthesis of PGD2 is associated with formation of 11-dehydro-TxB2 the investigators will measure prostaglandin metabolites in blood and urine of volunteers receiving niacin. In addition, subjects will be treated with low or high dose aspirin prior to niacin to analyze the contribution of cyclooxygenase enzymes to biosynthesis of PGD2.

Arm 1: Subjects will receive 500 mg niacin. The subjects will collect urine (3-10 ml each) before niacin and every one-two hours after niacin for 10 h. Subjects will have blood drawn (2 teaspoons) before and at 0.5-1 h after niacin.

Arm 2: Subjects will take 81 mg aspirin (1 tablet of low-dose aspirin) daily for 7 days before niacin. Urine collection will be before and after aspirin, before niacin, and then in intervals as in arm 1. There will be a blood collection before niacin and 0.5-1 h after niacin.

Arm 3: Subjects will take 325 mg aspirin (1 tablet of regular strength aspirin) daily for 7 days before niacin. Urine collection will be before and after aspirin, before niacin, and then in intervals as in arm 1.

Arm 4: Subjects will be infused with 10 μg of deuterated PGD2 in a forearm vein over the course of 30 min. Subjects will collect a urine sample before and every two hours after deuterated PGD2 for 10 h.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Normal, healthy volunteers not currently taking any medication.

Exclusion criteria

Use of anti-inflammatory/over-the-counter pain medications (NSAIDs) up to 2 weeks prior to study.

Treatment and study plan

niacin

Dietary Supplement

induce biosynthesis of PGD2

Aspirin

Drug

inhibition of cyclooxygenase

PGD2

Other

labeled precursor

Primary outcomes

prostaglandin metabolites

Time frame: 0-10 hours

metabolites will be quantified in urine and blood

Sponsors and collaborators

Lead sponsor

Vanderbilt University

Other

Collaborators

Vanderbilt University Medical Center

Registry information

Official study title

Novel Pathways of Eicosanoid Metabolism

Important dates

Study start: 2020
Primary completion: 2027
Study completion: 2027
First posted: Jul 9, 2020
Registry last updated: Jun 5, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.