Acetylsalicylic Acid and Colorectal Cancer Prevention: Exploring the Platelet Function of Its Mechanism of Action

NCT ID: NCT02125409

Last Updated: 2014-05-05

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-05-31

Brief 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%).

Conditions

Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Group 1

Group 1, individuals will be treated with ASA for 1 week; then blood and tissue samples (during the screening colonoscopy) will be collected at from 6-7 h after the last dose of ASA.

Group Type: EXPERIMENTAL

Acetylsalicylic acid

Intervention Type: DRUG

One tablet of Adiro 100 mg will be administered daily for 7 days.

Screening colonoscopy

Intervention Type: PROCEDURE

Group 2

Group 2, individuals will be treated with ASA for 1 week; then blood and tissue samples (during the screening colonoscopy) will be collected at 24 hours after the last dose.

Group Type: EXPERIMENTAL

Acetylsalicylic acid

Intervention Type: DRUG

One tablet of Adiro 100 mg will be administered daily for 7 days.

Screening colonoscopy

Intervention Type: PROCEDURE

Interventions

Acetylsalicylic acid

One tablet of Adiro 100 mg will be administered daily for 7 days.

Intervention Type: DRUG

Screening colonoscopy

Intervention Type: PROCEDURE

Other Intervention Names

Adiro 100; ASA

Eligibility Criteria

Inclusion Criteria

1. Men and women, aged ≥ 18 and ≤ 69.

2. Patients should have an indication for screening colonoscopy

1. First degree relative of patient with CRC.

2. Personal history of adenomas.

3. People older than 50 and FOBT positive

3. Routine hematological and biochemical parameters within the normal range.

Exclusion Criteria

1. Allergy to ASA or other NSAIDs.

2. Previous use of ASA, NSAIDS, antiplatelet agents, corticosteroids or misoprostol in the previous 15 days and/or anticipated need for these drugs during the study period.

3. Peptic ulcer history or any other gastrointestinal disease that could be considered a contraindication for ASA use without the concomitant use of a proton-pump inhibitor.

4. Subjects with coagulation disorder or serious comorbid condition.

5. Malignancies, excluding CRC, diagnosed in the previous 5 years

6. Cigarette smoking, history of drug or alcohol abuse

7. Pregnant women or breast feeding

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

G. d'Annunzio University

OTHER

Sponsor Role: collaborator

Catholic University, Italy

OTHER

Sponsor Role: collaborator

Aragon Institute of Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Angel Lanas Arbeloa, Physician

Role: PRINCIPAL_INVESTIGATOR

Digestive disease service of Hospital Clinico Lozano Blesa

Locations

Hospital Clínico Universitario Lozano Blesa

Zaragoza, Zaragoza, Spain

Countries

Spain

Facility Contacts

Angel Lanas Arbeloa, Physician

Role: primary

alanas@unizar.es

+34 976 765786

Other Identifiers

2013-004269-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D-13-01

Identifier Type: -

Identifier Source: org_study_id