Pathways of Eicosanoid Metabolism

Metabolism of Prostaglandin D2 Clinical Trial

Official title:

Novel Pathways of Eicosanoid Metabolism

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04464070
• Other study ID #: 150895
• Status: Enrolling by invitation
• Phase: Early Phase 1
• Start date: August 15, 2020
• Est. completion date: August 4, 2025

Study information

• Verified date: June 2024
• Source: Vanderbilt University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 10
• Est. completion date: August 4, 2025
• Est. primary completion date: May 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Metabolism of Prostaglandin D2

Intervention

Dietary Supplement:
• niacin
induce biosynthesis of PGD2

Drug:
• aspirin
inhibition of cyclooxygenase

Other:
• PGD2
labeled precursor

Locations

Country	Name	City	State
United States	Vanderbilt University	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt University	Vanderbilt University Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	prostaglandin metabolites	metabolites will be quantified in urine and blood	0-10 hours