ASCENT Trial Version 1
Research type
Research Study
Full title
Arginine Supplementation to improve Cardiovascular and Endothelial function after NSAID Treatment (ASCENT)
IRAS ID
280354
Contact name
Jane Mitchell
Contact email
Sponsor organisation
Imperial College
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 0 months, 0 days
Research summary
Summary of Research
Drugs like ibuprofen and celecoxib are some of the most commonly taken drugs. As a group, they are called nonsteroidal anti-inflammatory drugs (NSAIDs) and work by blocking an enzyme called COX-2. NSAIDs are good at treating inflammation and can prevent some cancers but they increase a person’s chance of having a heart attack or a stroke by as much as 30%. Based on the current information we have we cannot tell who will get a heart attack after taking NSAIDs. We will conduct a mechanistic healthy male volunteer study where participants take celecoxib for 7 days and measure the effects this may have on blood pressure, kidney function and blood vessel function. We will use cutting-edge technology that allows us to measure more than 22,000 substances in the blood of volunteers so that we can work out which of these might change when COX-2 is inhibited or be different in people who will go on to get a heart attack because of their NSAID medication. Research in our lab has found that blocking COX-2 increases the levels of a substance in the blood called asymmetric dimethylarginine (ADMA). ADMA reduces vascular health and is linked to heart attacks and strokes. Importantly the effects of ADMA could be prevented by L-arginine. We also want to see if taking L-arginine supplements with NSAIDs can reverse some of the potential negative effects. The study will take place at a NIHR Imperial clinical research facility and will take around 12 months to complete. We think that this work will allow us to design simple blood tests that would tell us which patients who take NSAIDs are at risk and provide new ideas about how to protect them. This test would also allow the majority of people not at risk to take their medication without worry.Summary of Results
Arginine Supplementation to improve Cardiovascular and Endothelial function after NSAID Treatment (ASCENT).The research was carried out by staff at Imperial College London funded by the British Heart Foundation between 2021 and 2022.
We already know how drugs like celecoxib (Non-steroidal anti-inflammatory drugs (NSAIDs), which include ibuprofen) work to reduce pain and inflammation. We also know that these drugs can cause an increase in the risk of cardiovascular events such as heart attacks or strokes and that this is particularly important for patients, such as those with arthritis, who need to take these drugs long term. There is much that we do not understand about how NSAIDs affect the cardiovascular system and we know very little about how these drugs affect proteins, gene expression or metabolites in the blood. In this study we have combined standard measurements of endothelial function, kidney function and blood pressure with a wide range of substances measured in the blood which will enable us to answer the question of ‘how do NSAIDs affect healthy people and what connections can we make with blood substances to find out how these drugs might affect the cardiovascular system’ This is important to find out because these drugs carry a small risk of cardiovascular events and because so many people take these drugs this small risk amounts to an important problem on a population level.
Healthy male volunteers participated in the study. There were no adverse reactions in either group of participants.
Participants had blood pressure and other standard clinical tests performed. Vascular function was measured, and blood samples were collected before and after each participant took either placebo or celecoxib for seven days. The study was conducted in a blinded manner which means that that neither the volunteers or the staff working with the volunteers or the scientists doing the analysis knew which group the results were from. Clinical measurements including blood pressure were generally not different in those taking placebo compared to celecoxib. However, there were differences in a measure of vascular health called augmentation index in the celecoxib group. The study has identified a new area of research that could help to explain how drugs like celecoxib affect the cardiovascular system. We are continuing to analyse samples from this study and with future studies this work could help understand which people may be at risk of cardiovascular events when taking NSAIDs. Key results from this study have been presented at the American Heart Association meeting and will be submitted to scientific journals. These will be made open access so that there is no cost to anyone wishing to read the reports.
REC name
London - Brighton & Sussex Research Ethics Committee
REC reference
20/PR/0378
Date of REC Opinion
12 Jan 2021
REC opinion
Further Information Favourable Opinion