Healthy
Conditions
Keywords
NSAID, Endothelial function, COX-2, Celecoxib, biomarker
Brief summary
A single centre, placebo controlled, blinded (participant, investigator, outcome assessor) trial to evaluate the effects of COX-2 inhibition with celecoxib on endothelial function in healthy male volunteers.
Detailed description
Primary Objective: To perform a systemic analysis of how COX-2 inhibition by celecoxib affects vascular function and 'omic biomarkers including those associated with the COX-2/prostacyclin/ADMA axis in healthy male volunteers Secondary Objective: To investigate how this is altered by L-arginine supplementation Methods: A single centre, double blind, placebo controlled trial will be carried out in healthy male volunteers between 18 and 40 years of age. In phase 1, participants will be blinded and randomised to receive either Celecoxib 200mgBD for 7 days or placebo. The primary endpoint is endothelial function measured by EndoPAT. In Phase 2, the same participants will receive either Celecoxib 200mgBD for 7 days + 10g L-arginine supplementation or placebo + 10g L-arginine supplementation to see if L-arginine can reverse any endothelial dysfunction caused by Celecoxib. Secondary outcomes will include measurement of 'omic biomarkers.
Interventions
DRUGCelecoxib
Two 200 mg capsules per day (400 mg/day) for 7 days
OTHERPlacebo
2 capsules/day for 7 days
OTHERL-arginine + placebo
L-arginine = Five capsules of 2 mg per day (10 mg/day) for 7 days Placebo = 2 capsules/day for 7 days
OTHERL-arginine + celecoxib
L-arginine = Five capsules of 2 mg per day (10 mg/day) Celecoxib = Two 200 mg capsules per day (400 mg/day) for 7 days
Sponsors
Imperial College London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Healthy male volunteers will be blinded and randomized to 7 days' treatment with celecoxib (200mg bd) or placebo.
Eligibility
Sex/Gender
MALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* No abnormal findings on medical history, screening physical examination, hematology, biochemistry, urinalysis (including specific gravity), and vital signs (sitting blood pressure, sitting pulse rate, sitting respiratory rate and body temperature) within 2 weeks of commencement of the study. * Normal fasting lipid profile * Non-smoking * Clear venous access in upper limbs * BMI: 18-30 * No history or signs of drug abuse * No other medication 4 weeks before or during the study * Informed written consent
Exclusion criteria
* Any history of allergy to NSAIDS or arginine * Significant medical conditions * Pulse rate \<50 bpm * Sitting systolic blood pressure \<80 or \>160 mmHg * Sitting diastolic pressure \<60 or \>100 mmHg * Baseline endothelial dysfunction (as defined by EndoPAT; LnRHI \<0.51) * Participation in other clinical study 8 weeks before or during the study * Donation of blood 8 weeks before or during the study * Those on medication that cannot be discontinued
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Log Reactive Hyperaemic Index | Baseline and 7 days | Measured using the EndoPAT 2000 device (which is an FDA approved medical device). Data are issued by the equipment as: LnRHI (Log Reactive hyperaemic index), a reduction from the individual participant baseline value indicates endothelial dysfunction |
| Augmentation Index | Baseline and 7 days | Measured using the EndoPAT 2000 device (which is an FDA approved medical device) at baseline and at 7 days. Data are issued by the equipment. Augmentation index (which is a surrogate for vascular stiffness). An increase indicates an increase in vascular stiffness. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Blood Pressure | Baseline and 7 Days | Participants will record their blood pressure daily using a home monitoring device at rest on day 1 (baseline) and day 7. Reported as change in systolic blood pressure (delta) from baseline. |
| Increase/Decrease of Cardiovascular Biomarkers From Baseline | Baseline and 7 days | Measured using mass spectrometry on serum samples collected at baseline and at 7 days. |
Countries
United Kingdom
Contacts
STUDY_DIRECTORJane Mitchell, Professor
Imperial College London
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Celecoxib Celecoxib | 20 |
| Placebo Placebo | 20 |
| Total | 40 |
Baseline characteristics
| Characteristic | Celecoxib | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 25.5 years STANDARD_DEVIATION 6 | 27.1 years STANDARD_DEVIATION 6 | 26.8 years STANDARD_DEVIATION 6.2 |
| Race/Ethnicity, Customized Asian | 4 Participants | 7 Participants | 11 Participants |
| Race/Ethnicity, Customized Mixed | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Oriental | 4 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 10 Participants | 10 Participants | 20 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 20 Participants | 20 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 0 / 20 | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Augmentation Index
Measured using the EndoPAT 2000 device (which is an FDA approved medical device) at baseline and at 7 days. Data are issued by the equipment. Augmentation index (which is a surrogate for vascular stiffness). An increase indicates an increase in vascular stiffness.
Time frame: Baseline and 7 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Celecoxib | Augmentation Index | 3.7 Augmentation Index | Standard Deviation 9.05 |
| Placebo | Augmentation Index | -2.54 Augmentation Index | Standard Deviation 10.24 |
Primary
Log Reactive Hyperaemic Index
Measured using the EndoPAT 2000 device (which is an FDA approved medical device). Data are issued by the equipment as: LnRHI (Log Reactive hyperaemic index), a reduction from the individual participant baseline value indicates endothelial dysfunction
Time frame: Baseline and 7 days
Population: Data presented as mean change from baseline (delta)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Celecoxib | Log Reactive Hyperaemic Index | 0.003 LnRHI (Log Reactive hyperaemic index) | Standard Deviation 0.35 |
| Placebo | Log Reactive Hyperaemic Index | 0.095 LnRHI (Log Reactive hyperaemic index) | Standard Deviation 0.33 |
Secondary
Blood Pressure
Participants will record their blood pressure daily using a home monitoring device at rest on day 1 (baseline) and day 7. Reported as change in systolic blood pressure (delta) from baseline.
Time frame: Baseline and 7 Days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Celecoxib | Blood Pressure | -1.45 mmHg | Standard Deviation 11.8 |
| Placebo | Blood Pressure | 2.03 mmHg | Standard Deviation 7.97 |
Secondary
Increase/Decrease of Cardiovascular Biomarkers From Baseline
Measured using mass spectrometry on serum samples collected at baseline and at 7 days.
Time frame: Baseline and 7 days