Study of Biochemical Markers to Determine the Acetylsalicylic Acid Chemopreventive Effect Through Antiplatelet Action

NCT02060396 | Completed Phase 1 DMC

• 2 other identifiers: D12-012012-004425-25
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This study in healthy volunteers is the first step in developing a collaborative research program, which seeks to test the hypothesis that chemopreventive effect of acetylsalicylic acid (ASA) on colon cancer is due predominantly to its antiplatelet effect. The following features of the clinical evidence are consistent with the platelet-mediated hypothesis:

1. 1.The apparent saturability of the chemopreventive effect of ASA at low doses given once daily, found in long-term analyses of cardiovascular and adenoma recurrence randomized clinical trial, as well as in the vast majority of observational studies performed in different settings and with different methodology. A remarkably similar saturability of the cardioprotective effect of low dose ASA given once daily is explained by the irreversible nature of cyclooxygenase (COX)-1 inactivation in platelets, and limited capacity of human platelets for de novo protein synthesis.
2. 2.Given the short half-life of ASA in the human circulation (approximately 20 min) and the capacity of nucleated cells to resynthesize the acetylated COX-isozyme(s), it seems unlikely that a nucleated target could be suppressed throughout the 24-h dosing interval.
3. 3.One of the cardiovascular randomized clinical trial (Thrombosis Prevention Trial) in which the chemopreventive effect of ASA was detected on long-term follow-up, involved the administration of a controlled-release formulation of ASA (75 mg) with negligible systemic bioavailability.
4. 4.Enhanced platelet activation and thromboxane (TX)A2 generation in vivo has been demonstrated in patients with colorectal cancer and in Familial Adenomatous Polyposis patients.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• Assessment of the extenet of acetylation at serine-529 of platelet COX-1 during 1 week

  For analysis of COX-1, peripheral blood samples (3ml) were extracted from each one of the subjects involved, and then divided into aliquots of 1 ml of blood fully and immediately be transferred into glass tubes let to coagulate at 37 °C for 60 minutes. The serum is separated by centrifugation (10 minutes at 3000 rpm) and stored at - 70 °C until analyzed the extent of actetylation at serine-529 of platelet COX-1. This variable will allow to determine the initial level of activity of COX-1 in patients for comparison after the acetylation degree produced by the low dose ASA.

  3 days before the 1st dose and at 0.5, 2, 4, 8 and 24 h after the 1st and the 7th daily dose of enteric-coated aspirin, blood samples will be collected to assess: - platelet COX-1 acetylation - serum TXB2 levels - whole blood aggregation

Secondary Outcomes (4)

• Change from baseline in quantification acetylation COX-1 in the circulating platelets during 1 week

  3 days before the 1st dose and at 0.5, 2, 4, 8 and 24 h after the 1st and the 7th dose of aspirin, blood samples will be collected to assess: - platelet COX-1 acetylation - serum TXB2 levels - whole blood aggregation

• Change from baseline in urinary levels of 11-dehydro-TXB2 (TX-M) during 1 week

  1 day before the 1st dose aspirin administration and after the 6thdose of aspirin, all subjects will perform a 24 h urine collection.

• Change from baseline in whole blood platelet aggregation during 1 week

  3 days before the 1st dose and at 0.5, 2, 4, 8 and 24 h after the 1st and the 7th dose of aspirin, blood samples will be collected to assess: - platelet COX-1 acetylation - serum TXB2 levels - whole blood aggregation

• Change from baseline in plasma levels of aspirin and salicylate during 1 week.

  On day 1 and day 7, at pre-drug (baseline) and at 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12 and 24 h after dosing all subjects will undergo a blood sample collection to assess: - aspirin and salicylate plasma levels.

Study Arms (1)

Acetylsalicylic acid

EXPERIMENTAL

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

Drug: Acetylsalicylic acid

Interventions

Acetylsalicylic acid DRUG

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

Also known as: Adiro 100

Acetylsalicylic acid

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Men and women, aged ≥ 18 and ≤ 45.
• No potential contraindication to ASA.
• Unaltered history and physical examination.
• Unchanged hematological and biochemical laboratory parameters.
• Hematological parameters consistent with the current rules for blood donation.
• Negative urine pregnancy test.
• Negative serology for HIV, hepatitis B and C, alcohol intake and drug abuse.

You may not qualify if:

• Active cigarette smokers.
• Coagulation disorders.
• Allergy to ASA or any other NSAID.
• History of any gastrointestinal disorder.
• Pregnant women

Sponsors & Collaborators

• Aragon Institute of Health Sciences: lead

Study Sites (1)

Hospital clinico Universitario Lozano Blesa

Zaragoza, Zaragoza, 50009, Spain

Location

MeSH Terms

Interventions

Aspirin

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Angel Lanas, Physician

  Digestive disease service of Hospital Clinico Lozano Blesa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2014
• First Posted: February 12, 2014
• Study Start: April 1, 2013
• Primary Completion: June 1, 2013
• Study Completion: December 1, 2013
• Last Updated: March 18, 2014

Record last verified: 2014-03

Locations

ES (1)