Lipidomics Screening of Anti-inflammatory Drugs and Drug Candidates in Vitro - Part A
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02095288|
Recruitment Status : Active, not recruiting
First Posted : March 24, 2014
Last Update Posted : August 17, 2022
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.
|Condition or disease||Intervention/treatment|
|Healthy||Procedure: Blood draw|
|Study Type :||Observational [Patient Registry]|
|Estimated Enrollment :||30 participants|
|Target Follow-Up Duration:||1 Day|
|Official Title:||Broad-spectrum Lipidomics Screening of Anti-inflammatory Drugs and Drug Candidates in In Vitro Human Whole-blood Assay (hWBA)|
|Study Start Date :||November 2013|
|Estimated Primary Completion Date :||June 2023|
|Estimated Study Completion Date :||July 2024|
Procedure: Blood draw
This is a single blood donation, no drugs or devices administered
Other Name: It's a single blood draw of 104 ml in total
- Quantification of lipids in plasma and serum from the whole blood treated with the test compounds [ Time Frame: Within a week after the blood draw ]
Biospecimen Retention: Samples Without DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02095288
|United States, Pennsylvania|
|The Clinical Translational Research Center (CTRC) at the Hospital of the University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|Principal Investigator:||Garret A FitzGerald, MD||University of Pennsylvania|