Aspirin SensitivityEarly Phase 1NCT04040465
Asprin Dosing Estimator in Healthy Adults
A Early Phase 1 study testing Aspirin in people with Aspirin Sensitivity, run by University of Utah at 1 site in United States.
Trial summary
Understanding sources of variability in human drug dosing is important to the beneficial and safe use of any drug. Understanding and applying the science of individualizing a drug dose to a patient is called precision medicine. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Aspirin Sensitivity
- What is being tested?
- Aspirin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Feb 2021to 30 Oct 2021
- Phase
- Early 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Ages 18-55 years old (male or female)
- Healthy Volunteers (medication free without acute or chronic significant health problems or pathologies)
Who cannot join
- History of asthma
- History of chronic bronchitis
- History of emphysema
- History of renal impairment (eGFR < 30 ml/min)
- History of hypertension (reviewed by study staff)
- History of hyperlipidemia
Show all 15Show fewer
- History of diabetes
- History of smoking (within last month)
- Current depression or anxiety requiring medication therapy
- Inability to finish the study for any reason
- Any current pathological condition outside of normal range
- Thrombocytopenia (platelet count < 150 K/µL)
- Other known platelet disorders (eg. von Willebrand disease, Glanzmann thrombasthenia, Bernard-Soulier Syndrome)
- Current use of dipyradamole, PGY 12 inhibitors, NSAIDs
- Or as otherwise determined by the investigative team
Trial locations and contacts
1 site in 1 country.
About this study
Understanding sources of variability in human drug dosing is important to the beneficial and safe use of any drug. Understanding and applying the science of individualizing a drug dose to a patient is called precision medicine.
Aspirin is one of the oldest most utilized medications for its ability to lower fever, relieve pain, and to reduce the stickiness of platelets (tiny blood cells that help your body form clots to stop bleeding. Aspirin dosing is currently the same for all patients and is not individualized. In the last century, aspirin has shown benefit in reducing cancer, stroke, and preventing cardiovascular events after one has already had a heart attack or stroke. Previous human studies have not found consistent positive effects of aspirin when dosed by body weight. Therefore, how should aspirin be dosed in 2019? Aspirin resistance is the failure of aspirin to reduce platelet stickiness and thin the blood and most importantly, is associated with higher risk of heart attacks and strokes. Aspirin resistance may occur due to not taking aspirin on a regular basis, differences in how platelets behave in some persons, use of over the counter pain medicines like Motrin®, reduced amount of drug in the body, and/or a lack of being able to predict a dose for a certain individual.
To find out the best way to dose aspirin, the investigators propose to study healthy volunteers (persons without any known disease) with different ages and body sizes to see if aspirin blood levels are tied to platelet stickiness. This information will be used to mathematically build a computer-based picture of aspirin dosing that will help physicians pick the best dose of aspirin for each patient. The investigators will then extend studies for the aspirin dose estimator to be used in other countries in people with heart problems and stroke, recording future events in a randomized (i.e., coin toss) manner, to determine if the ability of the aspirin dose estimator to prevent future heart attacks and stroke compared to people receiving aspirin doses that were chosen without the estimator.
Read the detailed description
AIM 1: Determine urine TXB2, platelet aggregation function testing (VerifyNow® ASA Test), salicylate level, CBC with differential, and hs-CRP, in 18 healthy volunteers across BMI classes of 22-25 (Normal Weight), >25-30 (Overweight), and > 30 kg/m2 (Obese).Total enrolled cohort: 60 patients and planned treatment cohort: 54 completed patients (anticipated dropout rate of 10% = 6 patients). The investigators have powered this sample size based on estimates of effect sizes from published studies examining platelet activation in patients across a range of BMIs and assuming an alpha = 0.05, with 80% power. In addition, height and weight as predictors will be evaluated independently of BMI. BMI patient groups (22-25, >25-30, and > 30 kg/m2) will be randomized to low-dose ASA (81mg standard-release), moderate dose ASA (325mg) or high dose ASA (500mg) (6 patients/each dose).
All patients will have a CBC with differential (to measure blood cell counts including platelets) and hs-CRP at baseline, serial urine TXB2 (-1, and 2 and 5 hours post ASA dose), platelet aggregation function testing using VerifyNow® ASA Test 15 min post ASA dose, serial salicylate levels (0, 15", 2 hours post-ASA dose) and again 10-14 days after chronic dosing (urine TXB2 2 hours post ASA dose and platelet aggregation function testing using VerifyNow® Test 15 min post ASA dose only).
AIM 2: Model associations between construct variables (BMI and aspirin dose) with predictive variables as collected in AIM 1. Multiple and Linear Regression with backward selection will be used. In addition, a Structured Equation Model will be applied to the data. Statistical assessment of model fit will be conducted for all models.
AIM 3: Build an Aspirin Dose Estimator to predict aspirin dosing. Model associations from AIM 2 will create demand estimates that will feed into a user-friendly aspirin dosage estimator. The simulator will comprise: 1) Entry: An entry screen. In this screen the user will enter the features of patient clinical information attributes. The user then clicks a 'run' button. 2) Demand Output: The simulator will then create an output screen that will show graphically aspirin dosing options.
- Conditions
- Aspirin Sensitivity
- Being tested
- Aspirin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AspirinDrug
Participants will be categorized into 3 BMI groups and will be randomly given various doses of aspirin to compare effectiveness and create a dosing regimen.
| Study group | Role | What they receive |
|---|---|---|
| Normal Weight/Low Dose Aspirin | Active comparator | BMI 22-25 kg/m^2 \& receiving 81mg Aspirin daily for 2 weeks Receives: Drug: Aspirin |
| Normal Weight/Normal Dose Aspirin | Active comparator | BMI 25-30 kg/m^2 \& receiving 325mg Aspirin daily for 2 weeks Receives: Drug: Aspirin |
| Normal Weight/High Dose Aspirin | Active comparator | BMI > 30 kg/m^2 \& receiving 500mg Aspirin daily for 2 weeks Receives: Drug: Aspirin |
| Overweight/Low Dose Aspirin | Active comparator | BMI 22-25 kg/m^2 \& receiving 81mg Aspirin daily for 2 weeks Receives: Drug: Aspirin |
| Overweight/Normal Dose Aspirin | Active comparator | BMI 25-30 kg/m^2 \& receiving 325mg Aspirin daily for 2 weeks Receives: Drug: Aspirin |
| Overweight/High Dose Aspirin | Active comparator | BMI > 30 kg/m^2 \& receiving 500mg Aspirin daily for 2 weeks Receives: Drug: Aspirin |
| Obese/Low Dose Aspirin | Active comparator | BMI 22-25 kg/m^2 \& receiving 81mg Aspirin daily for 2 weeks Receives: Drug: Aspirin |
| Obese/Normal Dose Aspirin | Active comparator | BMI 25-30 kg/m^2 \& receiving 325mg Aspirin daily for 2 weeks Receives: Drug: Aspirin |
| Obese/High Dose Aspirin | Active comparator | BMI > 30 kg/m^2 \& receiving 500mg Aspirin daily for 2 weeks Receives: Drug: Aspirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Height
Used to measure BMI
Measured: 2 weeks per participant
Weight
Used to measure BMI
Measured: 2 weeks per participant
Urine TBX2 Collection (Thromboxane levels)
Thromboxane levels measured for indicator of platelet aggregation function
Measured: 2 weeks per participant
Salicylate Levels
Used to measure amount of systemic aspirin to compare with TBX2 and BMI categories
Measured: 2 weeks per participant
Aspirin Reaction Units (ARU)
Number given from Verifynow device that will be used to determine platelet aggregation function by arachidonic acid induced aggregation
Measured: 2 weeks per participant
Secondary outcomes (5)
Complete Blood Count (CBC)
Safety measure labs taken on 2 visits
Measured: 2 weeks per participant
High-sensitivity C-reactive protein (hs-CRP)
Measured as an inflammatory marker and indicator of cardiac risk and risk of stroke
Measured: 2 weeks per participant
Blood Pressure (mmHg)
Safety measure taken on 2 visits
Measured: 2 weeks per participant
Heart Rate (BPM)
Safety measure taken on 2 visits
Measured: 2 weeks per participant
Respiratory Rate (breaths per minute)
Safety measure taken on 2 visits
Measured: 2 weeks per participant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2019
- Study start15 Feb 2021
- Primary completion30 Oct 2021
- Study completion30 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Aspirin SensitivityStudies of the same condition, open and under way.
- More trials run by University of UtahThe sponsor's other registered studies.
- 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
- Early Phase 1
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- We will place patients into 3 different groups based on BMI, and within those groups patients will be randomly assigned to an aspirin dose (81mg, 325mg, or 500mg)
- Masking
- None (open label)
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Collaborators
- University of Colorado, Denver
- Responsible party
- Principal investigator, mark munger, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04040465
- Sponsor's protocol ID
- IRB_00117303
- Status last verified
- Oct 2020
- First submitted
- 22 Jul 2019
- Last updated
- 11 Mar 2022
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Asprin Dosing Estimator in Healthy Adults
- ClinicalTrials.gov ID
- NCT04040465
- Acronym / sponsor ID
- IRB_00117303
- Conditions
- Aspirin Sensitivity
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Collaborators
- University of Colorado, Denver
- Study start
- 15 Feb 2021 (actual)
- Primary completion
- 30 Oct 2021 (actual)
- Study completion
- 30 Oct 2021 (actual)
- First posted
- 31 Jul 2019 (actual)
- 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.
Understanding sources of variability in human drug dosing is important to the beneficial and safe use of any drug. Understanding and applying the science of individualizing a drug dose to a patient is called precision medicine.
Aspirin is one of the oldest most utilized medications for its ability to lower fever, relieve pain, and to reduce the stickiness of platelets (tiny blood cells that help your body form clots to stop bleeding. Aspirin dosing is currently the same for all patients and is not individualized. In the last century, aspirin has shown benefit in reducing cancer, stroke, and preventing cardiovascular events after one has already had a heart attack or stroke. Previous human studies have not found consistent positive effects of aspirin when dosed by body weight. Therefore, how should aspirin be dosed in 2019? Aspirin resistance is the failure of aspirin to reduce platelet stickiness and thin the blood and most importantly, is associated with higher risk of heart attacks and strokes. Aspirin resistance may occur due to not taking aspirin on a regular basis, differences in how platelets behave in some persons, use of over the counter pain medicines like Motrin®, reduced amount of drug in the body, and/or a lack of being able to predict a dose for a certain individual.
To find out the best way to dose aspirin, the investigators propose to study healthy volunteers (persons without any known disease) with different ages and body sizes to see if aspirin blood levels are tied to platelet stickiness. This information will be used to mathematically build a computer-based picture of aspirin dosing that will help physicians pick the best dose of aspirin for each patient. The investigators will then extend studies for the aspirin dose estimator to be used in other countries in people with heart problems and stroke, recording future events in a randomized (i.e., coin toss) manner, to determine if the ability of the aspirin dose estimator to prevent future heart attacks and stroke compared to people receiving aspirin doses that were chosen without the estimator.
Detailed description
AIM 1: Determine urine TXB2, platelet aggregation function testing (VerifyNow® ASA Test), salicylate level, CBC with differential, and hs-CRP, in 18 healthy volunteers across BMI classes of 22-25 (Normal Weight), >25-30 (Overweight), and > 30 kg/m2 (Obese).Total enrolled cohort: 60 patients and planned treatment cohort: 54 completed patients (anticipated dropout rate of 10% = 6 patients). The investigators have powered this sample size based on estimates of effect sizes from published studies examining platelet activation in patients across a range of BMIs and assuming an alpha = 0.05, with 80% power. In addition, height and weight as predictors will be evaluated independently of BMI. BMI patient groups (22-25, >25-30, and > 30 kg/m2) will be randomized to low-dose ASA (81mg standard-release), moderate dose ASA (325mg) or high dose ASA (500mg) (6 patients/each dose).
All patients will have a CBC with differential (to measure blood cell counts including platelets) and hs-CRP at baseline, serial urine TXB2 (-1, and 2 and 5 hours post ASA dose), platelet aggregation function testing using VerifyNow® ASA Test 15 min post ASA dose, serial salicylate levels (0, 15", 2 hours post-ASA dose) and again 10-14 days after chronic dosing (urine TXB2 2 hours post ASA dose and platelet aggregation function testing using VerifyNow® Test 15 min post ASA dose only).
AIM 2: Model associations between construct variables (BMI and aspirin dose) with predictive variables as collected in AIM 1. Multiple and Linear Regression with backward selection will be used. In addition, a Structured Equation Model will be applied to the data. Statistical assessment of model fit will be conducted for all models.
AIM 3: Build an Aspirin Dose Estimator to predict aspirin dosing. Model associations from AIM 2 will create demand estimates that will feed into a user-friendly aspirin dosage estimator. The simulator will comprise: 1) Entry: An entry screen. In this screen the user will enter the features of patient clinical information attributes. The user then clicks a 'run' button. 2) Demand Output: The simulator will then create an output screen that will show graphically aspirin dosing options.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 9
- Model description
- We will place patients into 3 different groups based on BMI, and within those groups patients will be randomly assigned to an aspirin dose (81mg, 325mg, or 500mg)
| Arm | Type | Receives |
|---|---|---|
| Normal Weight/Low Dose Aspirin | Active comparator | Drug: AspirinBMI 22-25 kg/m^2 \& receiving 81mg Aspirin daily for 2 weeks |
| Normal Weight/Normal Dose Aspirin | Active comparator | Drug: AspirinBMI 25-30 kg/m^2 \& receiving 325mg Aspirin daily for 2 weeks |
| Normal Weight/High Dose Aspirin | Active comparator | Drug: AspirinBMI > 30 kg/m^2 \& receiving 500mg Aspirin daily for 2 weeks |
| Overweight/Low Dose Aspirin | Active comparator | Drug: AspirinBMI 22-25 kg/m^2 \& receiving 81mg Aspirin daily for 2 weeks |
| Overweight/Normal Dose Aspirin | Active comparator | Drug: AspirinBMI 25-30 kg/m^2 \& receiving 325mg Aspirin daily for 2 weeks |
| Overweight/High Dose Aspirin | Active comparator | Drug: AspirinBMI > 30 kg/m^2 \& receiving 500mg Aspirin daily for 2 weeks |
| Obese/Low Dose Aspirin | Active comparator | Drug: AspirinBMI 22-25 kg/m^2 \& receiving 81mg Aspirin daily for 2 weeks |
| Obese/Normal Dose Aspirin | Active comparator | Drug: AspirinBMI 25-30 kg/m^2 \& receiving 325mg Aspirin daily for 2 weeks |
| Obese/High Dose Aspirin | Active comparator | Drug: AspirinBMI > 30 kg/m^2 \& receiving 500mg Aspirin daily for 2 weeks |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Ages 18-55 years old (male or female)
- Healthy Volunteers (medication free without acute or chronic significant health problems or pathologies)
Key exclusion criteria (15 listed)
- History of asthma
- History of chronic bronchitis
- History of emphysema
- History of renal impairment (eGFR < 30 ml/min)
- History of hypertension (reviewed by study staff)
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 |
|---|---|---|
| AspirinParticipants will be categorized into 3 BMI groups and will be randomly given various doses of aspirin to compare effectiveness and create a dosing regimen. | Drug | Normal Weight/High Dose Aspirin, Normal Weight/Low Dose Aspirin, Normal Weight/Normal Dose Aspirin, Obese/High Dose Aspirin, Obese/Low Dose Aspirin, Obese/Normal Dose Aspirin, Overweight/High Dose Aspirin, Overweight/Low Dose Aspirin, Overweight/Normal Dose Aspirin |
Primary outcome
Height
Time frame: 2 weeks per participant
Used to measure BMI
Weight
Time frame: 2 weeks per participant
Used to measure BMI
Urine TBX2 Collection (Thromboxane levels)
Time frame: 2 weeks per participant
Thromboxane levels measured for indicator of platelet aggregation function
Salicylate Levels
Time frame: 2 weeks per participant
Used to measure amount of systemic aspirin to compare with TBX2 and BMI categories
Aspirin Reaction Units (ARU)
Time frame: 2 weeks per participant
Number given from Verifynow device that will be used to determine platelet aggregation function by arachidonic acid induced aggregation
5 secondary outcomes
Complete Blood Count (CBC)
Time frame: 2 weeks per participant
High-sensitivity C-reactive protein (hs-CRP)
Time frame: 2 weeks per participant
Blood Pressure (mmHg)
Time frame: 2 weeks per participant
Heart Rate (BPM)
Time frame: 2 weeks per participant
Respiratory Rate (breaths per minute)
Time frame: 2 weeks per participant
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 11 Mar 2022.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Aspirin in people with Aspirin Sensitivity, run by University of Utah at 1 site in United States.
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 2 inclusion and 15 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 11 Mar 2022. 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 United States. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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?
Height (time frame: 2 weeks per participant). The study lists 5 primary outcomes in all. 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 11 Mar 2022.