Colorectal CancerPhase 3NCT02125409
Acetylsalicylic Acid and Colorectal Cancer Prevention: Exploring the Platelet Function of Its Mechanism of Action
A Phase 3 study testing Acetylsalicylic acid and Screening colonoscopy in people with Colorectal Cancer, run by Aragon Institute of Health Sciences at 1 site in Spain.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 69 years
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Acetylsalicylic acid and Screening colonoscopy
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteSpain
- Study dates
- May 2014to May 2015
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 69 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women, aged ≥ 18 and ≤ 69.
- Patients should have an indication for screening colonoscopy
- First degree relative of patient with CRC.
- Personal history of adenomas.
- People older than 50 and FOBT positive
- Routine hematological and biochemical parameters within the normal range.
Who cannot join
- Allergy to ASA or other NSAIDs.
- 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.
- 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.
- Subjects with coagulation disorder or serious comorbid condition.
- Malignancies, excluding CRC, diagnosed in the previous 5 years
- Cigarette smoking, history of drug or alcohol abuse
- Pregnant women or breast feeding
Trial locations and contacts
1 site in 1 country.
Spain1 site
Hospital Clínico Universitario Lozano Blesa
Zaragoza, Zaragoza, 50009
Angel Lanas Arbeloa, Physician, +34 976 765786, alanas@unizar.es
Angel Lanas Arbeloa, Physician
About this study
Official title: Acetylsalicylic Acid and Colorectal Cancer Prevention: Exploring the Platelet Function of Its Mechanism of Action.
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
- Being tested
- Acetylsalicylic acid, Screening colonoscopy
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acetylsalicylic acidDrug
Also called Adiro 100, ASA
One tablet of Adiro 100 mg will be administered daily for 7 days.
Screening colonoscopyProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | 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. Receives: Drug: Acetylsalicylic acid; Procedure: Screening colonoscopy |
| Group 2 | Experimental | 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. Receives: Drug: Acetylsalicylic acid; Procedure: Screening colonoscopy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of the degree of COX-1 acetylation by ASA administered for 1 week.
It will be performed in platelets versus biopsies of the recto-colonic tissues.
Measured: 7 hours after the 7th daily dose (group 1) and 24 hours after the 7th daily dose (group 2)
Secondary outcomes (7)
Changes from baseline in different biomarkers.
It will be used a combining technique of liquid chromatography with mass spectrometry (LC-MS/MS) to quantify the level of acetylation of COX-1 in circulating platelets in subjects treated with ASA.
Parameters of the composite measure:
- haemochrome, AST, ALT, gamma-GT, alkaline phosphatase (AP), total bilirubin, total protein, glucose, creatinine, N, Na, K, Ca.
- urine analysis: pH, protein, albumin, glucose, RBC, bilirubin, nitrites, leucocytes and sediment.
Measured: pre-drug on day 0 and after the 7th daily dose (6 hours for Group 1 and 24 hours for Group 2)
Changes from baseline in eicosanoid generation in vivo by measuring urinary metabolites derived from COXs.
It will be performed by ultra-performance liquid chromatography tandem mass spectrometry-mass spectrometry (UPLC/MS/MS).
Measured: pre-drug on day 0 and after the 7th daily dose (6 hours for Group 1 and 24 hours for Group 2)
Changes in baseline platelet COX-1
By using human whole blood assay (serum TXB2) ex vivo
Measured: pre-drug on day 0 and after the 7th daily dose (6 hours for Group 1 and 24 hours for Group 2)
Change from baseline in plasma proteins of markers of angiogenesis.
In blood sample by using an antibody array kit and Sphingosine-1 Phosphate (S1P) by immunoassay.
Measured: pre-drug on day 0 and after the 7th daily dose (6 hours for Group 1 and 24 hours for Group 2)
Assessment of ASA plasma levels.
Will be performed whole blood aggregation test.
Measured: pre-drug on day 0 and after the 7th daily dose (6 hours for Group 1 and 24 hours for Group 2)
Changes from baseline of proteomic profile of selected angiogenesis factors, ie VEGF, FGF2, TGFbeta, EGF, PDGF, MMP, angiogenin, and angiogenesis inhibitors, ie endostatin, PF4, thrombospondin 1, alpha-macroglobulin, PAI 1 and angiostatin.
It will be done in isolated platelets by using an antibody array kit and Sphingosine-1 Phosphate (S1P) by immunoassay.
Measured: pre-drug on day 0 and after the 7th daily dose (6 hours for Group 1 and 24 hours for Group 2)
Change from baseline in eicosanoid biosynthesis and protein expression of markers of growth and progression of colorectal cancer (such as COX-2, NF-Kb and PI3K/Akt/mTOR pathway).
It will be done in normal tissues or pathological recto-colonic tissues.
Measured: pre-drug on day 0 and after the 7th daily dose (6 hours for Group 1 and 24 hours for Group 2)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2014 (estimated)
- Study startMay 2014
- Primary completionMay 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Aragon Institute of Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- G. d'Annunzio University, Catholic University, Italy
- Responsible party
- Sponsor
- Investigators
- Angel Lanas Arbeloa, Physician, Principal investigator, Digestive disease service of Hospital Clinico Lozano Blesa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02125409
- Sponsor's protocol ID
- D-13-01
- Other IDs
- 2013-004269-15
- Status last verified
- May 2014
- First submitted
- 25 Apr 2014
- Last updated
- 5 May 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acetylsalicylic Acid and Colorectal Cancer Prevention: Exploring the Platelet Function of Its Mechanism of Action.
- ClinicalTrials.gov ID
- NCT02125409
- Acronym / sponsor ID
- D-13-01
- Conditions
- Colorectal Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Aragon Institute of Health SciencesUniversity, hospital or other
- Collaborators
- G. d'Annunzio University, Catholic University, Italy
- Study start
- May 2014
- Primary completion
- May 2015 (estimated)
- First posted
- 29 Apr 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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%).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Drug: Acetylsalicylic acid, Procedure: Screening colonoscopyGroup 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 2 | Experimental | Drug: Acetylsalicylic acid, Procedure: Screening colonoscopyGroup 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. |
Who may qualify
- Ages
- 18 to 69 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Men and women, aged ≥ 18 and ≤ 69.
- Patients should have an indication for screening colonoscopy
- Routine hematological and biochemical parameters within the normal range.
Key exclusion criteria (7 listed)
- Allergy to ASA or other NSAIDs.
- 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.
- 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.
- Subjects with coagulation disorder or serious comorbid condition.
- Malignancies, excluding CRC, diagnosed in the previous 5 years
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Acetylsalicylic acidAlso: Adiro 100, ASAOne tablet of Adiro 100 mg will be administered daily for 7 days. | Drug | Group 1, Group 2 |
| Screening colonoscopy | Procedure or surgery | Group 1, Group 2 |
Primary outcome
Assessment of the degree of COX-1 acetylation by ASA administered for 1 week.
Time frame: 7 hours after the 7th daily dose (group 1) and 24 hours after the 7th daily dose (group 2)
It will be performed in platelets versus biopsies of the recto-colonic tissues.
7 secondary outcomes
Changes from baseline in different biomarkers.
Time frame: pre-drug on day 0 and after the 7th daily dose (6 hours for Group 1 and 24 hours for Group 2)
Changes from baseline in eicosanoid generation in vivo by measuring urinary metabolites derived from COXs.
Time frame: pre-drug on day 0 and after the 7th daily dose (6 hours for Group 1 and 24 hours for Group 2)
Changes in baseline platelet COX-1
Time frame: pre-drug on day 0 and after the 7th daily dose (6 hours for Group 1 and 24 hours for Group 2)
Change from baseline in plasma proteins of markers of angiogenesis.
Time frame: pre-drug on day 0 and after the 7th daily dose (6 hours for Group 1 and 24 hours for Group 2)
Assessment of ASA plasma levels.
Time frame: pre-drug on day 0 and after the 7th daily dose (6 hours for Group 1 and 24 hours for Group 2)
Changes from baseline of proteomic profile of selected angiogenesis factors, ie VEGF, FGF2, TGFbeta, EGF, PDGF, MMP, angiogenin, and angiogenesis inhibitors, ie endostatin, PF4, thrombospondin 1, alpha-macroglobulin, PAI 1 and angiostatin.
Time frame: pre-drug on day 0 and after the 7th daily dose (6 hours for Group 1 and 24 hours for Group 2)
Change from baseline in eicosanoid biosynthesis and protein expression of markers of growth and progression of colorectal cancer (such as COX-2, NF-Kb and PI3K/Akt/mTOR pathway).
Time frame: pre-drug on day 0 and after the 7th daily dose (6 hours for Group 1 and 24 hours for Group 2)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Angel Lanas Arbeloa, Physician principal investigator
Digestive disease service of Hospital Clinico Lozano Blesa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Acetylsalicylic acid and Screening colonoscopy in people with Colorectal Cancer, run by Aragon Institute of Health Sciences at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of the degree of COX-1 acetylation by ASA administered for 1 week. (time frame: 7 hours after the 7th daily dose (group 1) and 24 hours after the 7th daily dose (group 2)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 May 2014.