Pathways of Eicosanoid Metabolism

NCT04464070 | Enrolling By Invitation Early Phase 1 FDA Drug

• 1 other identifier: 150895
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Metabolism of Prostaglandin D2

Outcome Measures

Primary Outcomes (1)

• prostaglandin metabolites

  metabolites will be quantified in urine and blood

  0-10 hours

Study Arms (4)

niacin

EXPERIMENTAL

Blood (10 ml) will be drawn from the subject. Immediately before or after the blood draw the subject will collect a urine (3-10 ml) sample. After the baseline blood draw and the urine sample is collected the subject will take 500 mg of niacin. The niacin will not be an extended release formulation. Subjects will be encouraged to drink plenty of water during the study. Subjects are instructed to collect urine 1, 2, 4, 6, 8, and 10 hours after niacin administration. Subjects will collect their urine in separate plastic tubes that will be provided to them. Approximately 1-2 h after niacin administration a second blood sample (10 ml) will be drawn from the subject.

Dietary Supplement: niacin

niacin + low-dose aspirin

EXPERIMENTAL

Volunteers will provide a urine sample. They will receive 7 tablets of low-dose aspirin (81 mg) and be instructed to take one tablet daily for 7 days. On the seventh day, they return to have blood drawn, urine collected, and receive niacin as described in arm 1.

Dietary Supplement: niacin; Drug: aspirin

niacin + regular-strength aspirin

EXPERIMENTAL

Volunteers will provide a urine sample. They will receive 7 tablets of regular-strength aspirin (325 mg) and be instructed to take one tablet daily for 7 days. On the seventh day, they return to have blood drawn, urine collected, and receive niacin as described in arm 1.

Dietary Supplement: niacin; Drug: aspirin

deuterated PGD2

EXPERIMENTAL

Volunteers will come to the clinical research center. Volunteers will provide a urine sample. The volunteers will be fitted to record an electrocardiogram (ECG) and blood pressure. ECG will be recorded continuously. Blood pressure will be taken at baseline and every 10 minutes thereafter for one hour. The solution with deuterated PGD2 (10 microgram) will be infused over the course of 30 min. Volunteers will be monitored for 1 h after the end of the infusion, and volunteers will start collecting urine in intervals up to 10 h. Infusion of the deuterated PGD2 solution will be performed in the presence of a physician. The injection solution will be prepared by Vanderbilt University Medical Center (VUMC) Investigational Drug Services. The solution will be sterile and pyrogen free.

Other: PGD2

Interventions

niacin DIETARY_SUPPLEMENT

induce biosynthesis of PGD2

niacin; niacin + low-dose aspirin; niacin + regular-strength aspirin

aspirin DRUG

inhibition of cyclooxygenase

niacin + low-dose aspirin; niacin + regular-strength aspirin

PGD2 OTHER

labeled precursor

deuterated PGD2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Normal, healthy volunteers not currently taking any medication.

You may not qualify if:

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

Sponsors & Collaborators

• Vanderbilt University: lead
• Vanderbilt University Medical Center: collaborator

Study Sites (1)

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Interventions

Niacin; Aspirin; Prostaglandin D2

Intervention Hierarchy (Ancestors)

Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Prostaglandins D; Prostaglandins; Eicosanoids; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Autacoids; Inflammation Mediators; Biological Factors

Study Officials

• Claus M Schneider, PhD

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Pharmacology

Model Details: Participants may be participating in all 4 arms of the study or in less than 4 arms.

Study Record Dates

• First Submitted: July 1, 2020
• First Posted: July 9, 2020
• Study Start: August 15, 2020
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): August 31, 2027
• Last Updated: June 5, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: IPD will become available from the beginning of the study until completion.
• Access Criteria: Researchers need to make a justified request.

Locations

US (1)