Healthy VolunteersPhase 1NCT02060396
Study of Biochemical Markers to Determine the Acetylsalicylic Acid Chemopreventive Effect Through Antiplatelet Action
A Phase 1 study testing Acetylsalicylic acid in people with Healthy Volunteers, run by Aragon Institute of Health Sciences at 1 site in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Acetylsalicylic acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteSpain
- Study dates
- Apr 2013to Dec 2013
- Phase
- Phase 1
- 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- Active cigarette smokers.
- Coagulation disorders.
- Allergy to ASA or any other NSAID.
- History of any gastrointestinal disorder.
- Pregnant women
Trial locations and contacts
1 site in 1 country.
Spain1 site
Hospital clinico Universitario Lozano Blesa
Zaragoza, Zaragoza, 50009
About this study
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:
Read more
- 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.
- 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.
- 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.
- Enhanced platelet activation and thromboxane (TX)A2 generation in vivo has been demonstrated in patients with colorectal cancer and in Familial Adenomatous Polyposis patients.
So, the main objective of this study is to assess the extent of acetylation at serine-529 of platelet COX-1 after the 1st and 7th dose of low-doseof enteric-coated ASA 100 mg daily. Changes of this novel biomarker of ASA action will be correlated to other known parameters of ASA PK and PD: i) Tmax, Cmax and AUC of ASA and salicylate in the peripheral circulation after oral dosing; ii) time to obtain the maximal antiplatelet effect by ASA and its persistence throughout the dosing interval as assessed by measuring the inhibition of platelet COX-1 activity in whole blood ex vivo, the inhibition of platelet aggregation in whole blood ex vivo and the inhibition of the systemic generation of TXB2.
Read the detailed description
This study will be performed in healthy subjects, under fasting conditions, and it will allow to acquire more information on the pharmacokinetics (PK) and pharmacodynamics (PD) of low-dose enteric-coated ASA, and to characterize 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. This biomarker will be then used in another clinical study in the target population, i.e. FAP patients, treated with low-dose ASA which that will be performed by Prof Angel Lanas (University of Zaragoza, Spain).
Twenty four healthy volunteers recruited among the hospital and laboratory personnel will be enrolled and treated with ASA (100 mg enteric-coated tablet per day, Adiro) for 1 week.
Blood samples will be collected at baseline (before treatment) and at 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12 and 24 h after the first and the last dose of ASA to assess the extent of inhibition of serum TXB2, as an index of platelet COX-1 activity, and plasma levels of ASA and salicylate and the extent of COX-1 acetylation in circulating platelets. Moreover, the investigators will assess the extent of inhibition of platelet aggregation in whole blood by the PFA-100 system. Twenty four hours urine samples will be also collected to measure 11-dehydro-TXB2 (TX-M), an index of systemic TXA2 biosynthesis in vivo.
Healthy subjects will take their daily ASA under fasting conditions and will abstain from the use of ASA and other NSAIDs for at least 2 weeks before enrolment.
All volunteers will be attended at the Clinical Research Unit of the University Hospital Lozano Blesa.
- Conditions
- Healthy Volunteers
- Being tested
- Acetylsalicylic acid
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
One tablet of Adiro 100 mg will be administered daily orally for 7 days.
| Study group | Role | What they receive |
|---|---|---|
| Acetylsalicylic acid | Experimental | One tablet of Adiro 100 mg will be administered daily orally for 7 days. Receives: Drug: Acetylsalicylic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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
Aliquots of 40 mL of urine was stored and keep at -70 °C until evaluation of urinary levels of TX-M, which will be corrected with urinary creatinine values. This variable will enable us to measure the degree of inhibition of TX systemic levels produced by the administration of low dose ASA, comparing the degree of inhibition after administration of ASA at doses of 100 mg / day.
Measured: 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
Study of platelet aggregation in whole blood (2ml) by a Platelet Function Analyzer-100 system (PFA-100). Using this technique we intend to assess the degree of inhibition produced by ASA in doses of 100 mg / day in the ex vivo platelet aggregation simulating the more accurately the conditions present in the bloodstream.
Measured: 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.
Blood samples (7 mL) will be collected , at time points after administration of 100 mg / day of ASA. The tubes will be centrifuged at 3200rpm for 10 minutes at 4 °C and plasma collected. Immediately after collection, plasma aliquots of 500 ul will be subjected to chromatography and stored frozen at -70 ° C until use. Aliquots of 200 uL will be combined with 20 uL of internal standard solution. The samples will be clarified by adding acetonitrile / DMSO with the help of vortex mixing and centrifugation at 3000 rpm for 10 min. The clarified supernate will be separated from the precipitate and analyzed using LC-MS/MS technique. This technique allows to see exactly plasma levels of both ASA and salicylate at different times of the study to know the pattern of metabolism of AAS and useful information on the Tmax, Cmax and AUC ASA salicylates.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2014 (estimated)
- Study startApr 2013
- Primary completionJun 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy VolunteersStudies 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 1
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aragon Institute of Health Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Angel Lanas, Physician, Principal investigator, Digestive disease service of Hospital Clinico Lozano Blesa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02060396
- Sponsor's protocol ID
- D12-01
- Other IDs
- 2012-004425-25
- Status last verified
- Mar 2014
- First submitted
- 6 Feb 2014
- Last updated
- 18 Mar 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Biochemical Markers to Determine the Acetylsalicylic Acid Chemopreventive Effect Through Antiplatelet Action
- ClinicalTrials.gov ID
- NCT02060396
- Acronym / sponsor ID
- D12-01
- Conditions
- Healthy Volunteers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Aragon Institute of Health SciencesUniversity, hospital or other
- Study start
- Apr 2013
- Primary completion
- Jun 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 12 Feb 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.
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:
- 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.
- 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.
- 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.
- Enhanced platelet activation and thromboxane (TX)A2 generation in vivo has been demonstrated in patients with colorectal cancer and in Familial Adenomatous Polyposis patients.
So, the main objective of this study is to assess the extent of acetylation at serine-529 of platelet COX-1 after the 1st and 7th dose of low-doseof enteric-coated ASA 100 mg daily. Changes of this novel biomarker of ASA action will be correlated to other known parameters of ASA PK and PD: i) Tmax, Cmax and AUC of ASA and salicylate in the peripheral circulation after oral dosing; ii) time to obtain the maximal antiplatelet effect by ASA and its persistence throughout the dosing interval as assessed by measuring the inhibition of platelet COX-1 activity in whole blood ex vivo, the inhibition of platelet aggregation in whole blood ex vivo and the inhibition of the systemic generation of TXB2.
Detailed description
This study will be performed in healthy subjects, under fasting conditions, and it will allow to acquire more information on the pharmacokinetics (PK) and pharmacodynamics (PD) of low-dose enteric-coated ASA, and to characterize 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. This biomarker will be then used in another clinical study in the target population, i.e. FAP patients, treated with low-dose ASA which that will be performed by Prof Angel Lanas (University of Zaragoza, Spain).
Twenty four healthy volunteers recruited among the hospital and laboratory personnel will be enrolled and treated with ASA (100 mg enteric-coated tablet per day, Adiro) for 1 week.
Blood samples will be collected at baseline (before treatment) and at 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12 and 24 h after the first and the last dose of ASA to assess the extent of inhibition of serum TXB2, as an index of platelet COX-1 activity, and plasma levels of ASA and salicylate and the extent of COX-1 acetylation in circulating platelets. Moreover, the investigators will assess the extent of inhibition of platelet aggregation in whole blood by the PFA-100 system. Twenty four hours urine samples will be also collected to measure 11-dehydro-TXB2 (TX-M), an index of systemic TXA2 biosynthesis in vivo.
Healthy subjects will take their daily ASA under fasting conditions and will abstain from the use of ASA and other NSAIDs for at least 2 weeks before enrolment.
All volunteers will be attended at the Clinical Research Unit of the University Hospital Lozano Blesa.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Acetylsalicylic acid | Experimental | Drug: Acetylsalicylic acidOne tablet of Adiro 100 mg will be administered daily orally for 7 days. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (5 listed)
- Active cigarette smokers.
- Coagulation disorders.
- Allergy to ASA or any other NSAID.
- History of any gastrointestinal disorder.
- Pregnant women
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 100One tablet of Adiro 100 mg will be administered daily orally for 7 days. | Drug | Acetylsalicylic acid |
Primary outcome
Assessment of the extenet of acetylation at serine-529 of platelet COX-1 during 1 week
Time frame: 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
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.
4 secondary outcomes
Change from baseline in quantification acetylation COX-1 in the circulating platelets during 1 week
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2014.
Related trials for Healthy Volunteers
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis
Not yet recruitingObservational study
Establishment of Biobank of Nasal Epithelium Samples From Healthy Volunteers
Healthy
RecruitingObservational study
Improved Methods of Cell Selection for Bone Marrow Transplant Alternatives
Graft-Versus-Host Disease, Graft-versus-leukemia
Not yet recruitingObservational study
Screening Protocol
Pain
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, 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 1 study testing Acetylsalicylic acid in people with Healthy Volunteers, 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 7 inclusion and 5 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: finished, as of the sponsor's last update on 18 Mar 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of the extenet of acetylation at serine-529 of platelet COX-1 during 1 week (time frame: 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). 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 18 Mar 2014.