Lipidomics Screening of Anti-inflammatory Drugs and Drug Candidates in Vitro - Part A

NCT02095288 | Active Not Recruiting

• 1 other identifier: 818658
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Cardiovascular complications of NSAIDs, selective for inhibition of COX-2, stimulated interest in microsomal prostaglandin E synthase-1 (mPGES-1) as an alternative drug target. Global deletion of mPGES-1 in mice suppresses PGE2 and augments PGI2 by PGH2 substrate rediversion. Unlike COX-2 inhibition or gene deletion, mPGES-1 deletion does not cause a predisposition to thrombogenesis and hypertension. However, cell-specific deletion of mPGES-1 reveals that the predominant substrate rediversion product amongst the prostaglandins varies by cell type, complicating drug development. We have developed an ultra performance liquid chromatography/ tandem mass spectrometry (UPLC-MS/MS) technique that allows the quantification of a wide range of lipids beyond the prostaglandin pathway (leukotrienes, anandamide and the 2-arachidonylglycerol cascades). This study is designed to examine different pathway interventions from the arachidonic acid cascade by anti-inflammatory compounds (with a focus on mPGES-1 inhibition) in whole human blood in vitro (Part A) and ex vivo (Part B). In Part A, whole human blood will be donated by healthy volunteers and treated with screening compounds in vitro (outside of the body). Experiments will be performed to measure an array of lipids in plasma and serum from pre-stimulated whole blood treated with a single or a combination of the test compounds. This study may reveal pathways previously unknown to be affected by the existing anti-inflammatory drugs and drug candidates, and will possibly suggest new indications and/or side effects.

Conditions

Healthy

Keywords

lipidomics; in vitro human whole blood assay; anti-inflammatory drugs; Lipidomics screening of anti-inflammatory drugs

Outcome Measures

Primary Outcomes (1)

• Quantification of lipids in plasma and serum from the whole blood treated with the test compounds

  Within a week after the blood draw

Study Arms (1)

Healthy volunteers

Blood draw

Procedure: Blood draw

Interventions

Blood draw PROCEDURE

This is a single blood donation, no drugs or devices administered

Also known as: It's a single blood draw of 104 ml in total

Healthy volunteers

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Normal, healthy, non-smoking, male and non-pregnant female volunteers between the ages of 18 - 50

You may qualify if:

• age between 18-50
• non-pregnant females
• non-smoking males and females
• in good health as based on medical history

You may not qualify if:

• Subjects with any medical condition, which 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 aspirin or aspirin containing products for at least two weeks prior to the study.
• Subjects who have taken acetaminophen, NSAIDs, COX-2 inhibitors (OTC or prescription) for at least two weeks prior to the study.
• Subjects who are consuming any type of tobacco product(s).
• Subjects who consume high doses of antioxidant vitamins daily (vitamin C\> 1000mg, Vitamin E\> 400IU, Beta Carotene\> 1000IU, Vitamin A\> 5000IU, Selenium\> 200mcg, Folic Acid\> 1mg) for the two 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 the study.
• Pregnant female subjects

Sponsors & Collaborators

• University of Pennsylvania: lead
• Eli Lilly and Company: collaborator

Study Sites (1)

The Clinical Translational Research Center (CTRC) at the Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Mazaleuskaya LL, Salamatipour A, Sarantopoulou D, Weng L, FitzGerald GA, Blair IA, Mesaros C. Analysis of HETEs in human whole blood by chiral UHPLC-ECAPCI/HRMS. J Lipid Res. 2018 Mar;59(3):564-575. doi: 10.1194/jlr.D081414. Epub 2018 Jan 4.

  PMID: 29301865 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Thirty (n=30) healthy, non-smoking male and female volunteers between the ages of 18-50 will be included in this study. If all inclusion/exclusion criteria are met, a blood collection of 104 ml will be obtained and the study visit will be completed. If eligible, a volunteer may participate in this study up to four separate times, but not more than two times in the same week.

MeSH Terms

Interventions

Blood Specimen Collection

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Garret A FitzGerald, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Target Duration: 1 Day
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2014
• First Posted: March 24, 2014
• Study Start: November 1, 2013
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): July 1, 2029
• Last Updated: January 23, 2026

Record last verified: 2026-01

Locations

US (1)