Lipidomics Screening of Celecoxib in ex Vivo Human Whole Blood Assay - Part B

• Status: Completed
• Trial end date: 2015-11-01
• Target enrollment: 0
• Participant gender: All

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 prostaglandin (PG) E2 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 among the prostaglandins varies by cell type, complicating drug development. The research team has 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 B, healthy volunteers will be asked to take a single, therapeutic dose of celecoxib and blood and urine samples will be collected before and after drug administration. Collected blood will be stimulated ex vivo, and lipids and their metabolites will be measured in blood and urine, respectively. The investigators expect that lipid profile from ex vivo hWBA done on celecoxib-treated subjects will recapitulate findings from the in vitro hWBA received with celecoxib-treated human blood (Part A).

• Phase: N/A
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Pennsylvania
• Collaborator: Eli Lilly and Company
• Treatments: Celecoxib

Criteria

Inclusion Criteria:

• Age between 18 - 50

• Volunteers must be in good health as based on medical history

• All volunteers must be non-smoking and non-pregnant

Exclusion Criteria:

• 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 (cancer or history of significant cardiovascular disease (including stroke or TIA), renal, hepatic, gastrointestinal, respiratory, endocrine, metabolic, hematopoietic, or neurological disorders).

• Subjects who have received an experimental drug within 30 days prior to the study

• Subjects who have taken medications at least two weeks prior to the study. Subjects using hormonal birth control, however, will not be an exclusionary criterion.

• Subjects who have taken aspirin or aspirin containing products for at least two weeks prior to the study.

• Subjects who are sensitive or allergic to celecoxib (Celebrex) or its components

• Subjects who have taken any formulation of celecoxib including but not limited to Celebrex, Celebra, Onsenal for at least two weeks prior to the start of the study and throughout 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.