Acetylsalicylic Acid and Colorectal Cancer Prevention: Exploring the Platelet Function of Its Mechanism of Action
Status:
Unknown status
Trial end date:
1969-12-31
Target enrollment:
Participant gender:
Summary
In a preliminary study in healthy subjects, the investigators determined the pharmacokinetic
and pharmacodynamic of enteric-coated acetylsalicylic acid (ASA) (Adiro 100 mg, Bayer), and
the variability (coefficient of variation), accuracy and precision of a novel biomarker of
ASA action, i.e., quantification of the extent of COX-1 acetylation at serine-529, using a
stable isotope dilution liquid chromatography multiple reaction monitoring/mass spectrometry
(LC-MS) technique.
Now, the investigators will perform a clinical study in individuals undergoing Colorectal
cancer (CRC) to validate the hypothesis that that low-dose ASA given once daily is acting
primarily by selectively acetylating platelet COX-1 and suppressing its activity throughout
the 24-hour dosing interval. In contrast, it is expected that the inhibitory effect on
extra-platelet sources of COX-1 will be short-lasting, if any, affecting only partially
COX-1, and this effect will be completely reversed at 24 hours after dosing. This is an
important point which will strengthen the platelet hypothesis underpinning the apparent
adequacy of a 24-hour dosing interval of ASA administration for the anticancer effect
detected in cardiovascular trials.
These patients will be stratified into individuals with adenomas/carcinomas (20 to 30%) and
patients without clinically detected adenomas/carcinomas (about 70 to 80%).
Phase:
Phase 3
Details
Lead Sponsor:
Aragon Institute of Health Sciences
Collaborators:
Catholic University, Italy G. d'Annunzio University