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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-004269-15 | EudraCT Number |
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| Name | Class |
|---|---|
| G. d'Annunzio University | OTHER |
| Catholic University, Italy | OTHER |
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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%).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Acetylsalicylic acid | Drug | One tablet of Adiro 100 mg will be administered daily for 7 days. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | 7 hours after the 7th daily dose (group 1) and 24 hours after the 7th daily dose (group 2) |
| Measure | Description | Time Frame |
|---|---|---|
| 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:
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Inclusion Criteria:
Men and women, aged ≥ 18 and ≤ 69.
Patients should have an indication for screening colonoscopy
Routine hematological and biochemical parameters within the normal range.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Angel Lanas Arbeloa, Physician | Digestive disease service of Hospital Clinico Lozano Blesa | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital ClÃnico Universitario Lozano Blesa | Zaragoza | Zaragoza | 50009 | Spain |
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| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
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| ID | Term |
|---|---|
| D001241 | Aspirin |
| ID | Term |
|---|---|
| D012459 | Salicylates |
| D062385 | Hydroxybenzoates |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
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| Screening colonoscopy | Procedure |
|
| 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). | 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 | 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. | 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. | 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. | 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. | pre-drug on day 0 and after the 7th daily dose (6 hours for Group 1 and 24 hours for Group 2) |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D006841 |
| Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |