HealthyPhase 4ASCENTNCT04765644
Arginine Supplementation to Improve Cardiovascular and Endothelial Function After NSAID Treatment
A Phase 4 study testing Celecoxib and L-arginine + celecoxib in people with Healthy, run by Imperial College London at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 40 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Celecoxib and L-arginine + celecoxib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 10 Jun 2021to 24 Jan 2022
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 40 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Imperial College Clinical Research Facility
London, w12 0HS
About this study
Official title: Arginine Supplementation to Improve Cardiovascular and Endothelial Function After NSAID Treatment (ASCENT)
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.
Read the 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.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CelecoxibDrug
Also called Celebrex
Two 200 mg capsules per day (400 mg/day) for 7 days
PlaceboOther
2 capsules/day for 7 days
L-arginine + placeboOther
L-arginine = Five capsules of 2 mg per day (10 mg/day) for 7 days Placebo = 2 capsules/day for 7 days
L-arginine + celecoxibOther
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
| Study group | Role | What they receive |
|---|---|---|
| Celecoxib | Active comparator | Phase 1: Twenty volunteers will receive celecoxib 200 mg, 2 times/day (total 400 mg/day) for 7 days. At this point, the study team will perform an interim analysis of the data. If our primary endpoint is not achieved we may revise our endpoints and/or if additional power is required, we may recruit up to an additional n=20 volunteers per group. This analysis may also serve as a stop-go checkpoint for continuation of the second phase of the study. If we do not see any effects of celecoxib on endothelial or cardiovascular function, we will not proceed to phase 2. If we do see a negative effect, we will proceed to phase 2.
In phase 2 participants will be re-invited to the study site following a 4-8 week washout period. Participants will then receive either treatment with placebo + 10g L-arginine supplementation (20 participants) or celecoxib + 10g arginine supplementation (20 participants) for a total of 7 days Receives: Drug: Celecoxib; Other: L-arginine + celecoxib |
| Placebo | Placebo comparator | Phase 1: Twenty volunteers will receive a placebo capsule, 2 times/day (total 400 mg/day) for 7 days. At this point, the study team will perform an interim analysis of the data. If our primary endpoint is not achieved we may revise our endpoints and/or if additional power is required, we may recruit up to an additional n=20 volunteers per group. This analysis may also serve as a stop-go checkpoint for continuation of the second phase of the study. If we do not see any effects of celecoxib on endothelial or cardiovascular function, we will not proceed to phase 2. If we do see a negative effect, we will proceed to phase 2.
In phase 2 participants will be re-invited to the study site following a 4-8 week washout period. Participants will then receive either treatment with placebo + 10g L-arginine supplementation (20 participants) or celecoxib + 10g arginine supplementation (20 participants) for a total of 7 days Receives: Other: Placebo; Other: L-arginine + placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline and 7 days
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.
Measured: Baseline and 7 days
Secondary outcomes (2)
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.
Measured: Baseline and 7 Days
Increase/Decrease of Cardiovascular Biomarkers From Baseline
Measured using mass spectrometry on serum samples collected at baseline and at 7 days.
Measured: Baseline and 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2021
- Study start10 Jun 2021
- Primary completion24 Jan 2022
- Study completion24 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe 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
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Healthy male volunteers will be blinded and randomized to 7 days' treatment with celecoxib (200mg bd) or placebo.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jane Mitchell, Professor, Study director, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04765644
- Sponsor's protocol ID
- 18IC4757
- Acronym
- ASCENT
- Status last verified
- Mar 2026
- First submitted
- 17 Feb 2021
- Last updated
- 17 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kirkby NS, Zaiss AK, Urquhart P, Jiao J, Austin PJ, Al-Yamani M, Lundberg MH, MacKenzie LS, Warner TD, Nicolaou A, Herschman HR, Mitchell JA. LC-MS/MS confirms that COX-1 drives vascular prostacyclin whilst gene expression pattern reveals non-vascular sites of COX-2 expression. PLoS One. 2013 Jul 9;8(7):e69524. doi: 10.1371/journal.pone.0069524. Print 2013.
PubMed 23874970Kirkby NS, Chan MV, Zaiss AK, Garcia-Vaz E, Jiao J, Berglund LM, Verdu EF, Ahmetaj-Shala B, Wallace JL, Herschman HR, Gomez MF, Mitchell JA. Systematic study of constitutive cyclooxygenase-2 expression: Role of NF-kappaB and NFAT transcriptional pathways. Proc Natl Acad Sci U S A. 2016 Jan 12;113(2):434-9. doi: 10.1073/pnas.1517642113. Epub 2015 Dec 28.
PubMed 26712011Warner TD, Mitchell JA. COX-2 selectivity alone does not define the cardiovascular risks associated with non-steroidal anti-inflammatory drugs. Lancet. 2008 Jan 19;371(9608):270-3. doi: 10.1016/S0140-6736(08)60137-3. No abstract available.
PubMed 18207021Kirkby NS, Lundberg MH, Chan MV, Vojnovic I, Solomon AB, Emerson M, Mitchell JA, Warner TD. Blockade of the purinergic P2Y12 receptor greatly increases the platelet inhibitory actions of nitric oxide. Proc Natl Acad Sci U S A. 2013 Sep 24;110(39):15782-7. doi: 10.1073/pnas.1218880110. Epub 2013 Sep 3.
PubMed 24003163Ahmetaj-Shala B, Kirkby NS, Knowles R, Al'Yamani M, Mazi S, Wang Z, Tucker AT, Mackenzie L, Armstrong PC, Nusing RM, Tomlinson JA, Warner TD, Leiper J, Mitchell JA. Evidence that links loss of cyclooxygenase-2 with increased asymmetric dimethylarginine: novel explanation of cardiovascular side effects associated with anti-inflammatory drugs. Circulation. 2015 Feb 17;131(7):633-42. doi: 10.1161/CIRCULATIONAHA.114.011591. Epub 2014 Dec 9.
PubMed 25492024
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Arginine Supplementation to Improve Cardiovascular and Endothelial Function After NSAID Treatment (ASCENT)
- ClinicalTrials.gov ID
- NCT04765644
- Acronym / sponsor ID
- ASCENT / 18IC4757
- Conditions
- Healthy
- Keywords
- NSAID, Endothelial function, COX-2, Celecoxib, biomarker
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- 10 Jun 2021 (actual)
- Primary completion
- 24 Jan 2022 (actual)
- Study completion
- 24 Jan 2022 (actual)
- First posted
- 21 Feb 2021 (actual)
- Results
- Posted 28 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Healthy male volunteers will be blinded and randomized to 7 days' treatment with celecoxib (200mg bd) or placebo.
| Arm | Type | Receives |
|---|---|---|
| Celecoxib | Active comparator | Drug: Celecoxib, Other: L-arginine + celecoxibPhase 1: Twenty volunteers will receive celecoxib 200 mg, 2 times/day (total 400 mg/day) for 7 days. At this point, the study team will perform an interim analysis of the data. If our primary endpoint is not achieved we may revise our endpoints and/or if additional power is required, we may recruit up to an additional n=20 volunteers per group. This analysis may also serve as a stop-go checkpoint for continuation of the second phase of the study. If we do not see any effects of celecoxib on endothelial or cardiovascular function, we will not proceed to phase 2. If we do see a negative effect, we will proceed to phase 2. In phase 2 participants will be re-invited to the study site following a 4-8 week washout period. Participants will then receive either treatment with placebo + 10g L-arginine supplementation (20 participants) or celecoxib + 10g arginine supplementation (20 participants) for a total of 7 days |
| Placebo | Placebo comparator | Other: Placebo, Other: L-arginine + placeboPhase 1: Twenty volunteers will receive a placebo capsule, 2 times/day (total 400 mg/day) for 7 days. At this point, the study team will perform an interim analysis of the data. If our primary endpoint is not achieved we may revise our endpoints and/or if additional power is required, we may recruit up to an additional n=20 volunteers per group. This analysis may also serve as a stop-go checkpoint for continuation of the second phase of the study. If we do not see any effects of celecoxib on endothelial or cardiovascular function, we will not proceed to phase 2. If we do see a negative effect, we will proceed to phase 2. In phase 2 participants will be re-invited to the study site following a 4-8 week washout period. Participants will then receive either treatment with placebo + 10g L-arginine supplementation (20 participants) or celecoxib + 10g arginine supplementation (20 participants) for a total of 7 days |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (9 listed)
- 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
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 |
|---|---|---|
| CelecoxibAlso: CelebrexTwo 200 mg capsules per day (400 mg/day) for 7 days | Drug | Celecoxib |
| Placebo2 capsules/day for 7 days | Other | Placebo |
| L-arginine + placeboL-arginine = Five capsules of 2 mg per day (10 mg/day) for 7 days Placebo = 2 capsules/day for 7 days | Other | Placebo |
| L-arginine + celecoxibL-arginine = Five capsules of 2 mg per day (10 mg/day) Celecoxib = Two 200 mg capsules per day (400 mg/day) for 7 days | Other | Celecoxib |
Primary outcome
Log Reactive Hyperaemic Index
Time frame: 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
Time frame: 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.
2 secondary outcomes
Blood Pressure
Time frame: Baseline and 7 Days
Increase/Decrease of Cardiovascular Biomarkers From Baseline
Time frame: Baseline and 7 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23874970Kirkby NS, Zaiss AK, Urquhart P, Jiao J, Austin PJ, Al-Yamani M, Lundberg MH, MacKenzie LS, Warner TD, Nicolaou A, Herschman HR, Mitchell JA. LC-MS/MS confirms that COX-1 drives vascular prostacyclin whilst gene expression pattern reveals non-vascular sites of COX-2 expression. PLoS One. 2013 Jul 9;8(7):e69524. doi: 10.1371/journal.pone.0069524. Print 2013.
- Background: PubMed 26712011Kirkby NS, Chan MV, Zaiss AK, Garcia-Vaz E, Jiao J, Berglund LM, Verdu EF, Ahmetaj-Shala B, Wallace JL, Herschman HR, Gomez MF, Mitchell JA. Systematic study of constitutive cyclooxygenase-2 expression: Role of NF-kappaB and NFAT transcriptional pathways. Proc Natl Acad Sci U S A. 2016 Jan 12;113(2):434-9. doi: 10.1073/pnas.1517642113. Epub 2015 Dec 28.
- Background: PubMed 18207021Warner TD, Mitchell JA. COX-2 selectivity alone does not define the cardiovascular risks associated with non-steroidal anti-inflammatory drugs. Lancet. 2008 Jan 19;371(9608):270-3. doi: 10.1016/S0140-6736(08)60137-3. No abstract available.
- Background: PubMed 24003163Kirkby NS, Lundberg MH, Chan MV, Vojnovic I, Solomon AB, Emerson M, Mitchell JA, Warner TD. Blockade of the purinergic P2Y12 receptor greatly increases the platelet inhibitory actions of nitric oxide. Proc Natl Acad Sci U S A. 2013 Sep 24;110(39):15782-7. doi: 10.1073/pnas.1218880110. Epub 2013 Sep 3.
- Background: PubMed 25492024Ahmetaj-Shala B, Kirkby NS, Knowles R, Al'Yamani M, Mazi S, Wang Z, Tucker AT, Mackenzie L, Armstrong PC, Nusing RM, Tomlinson JA, Warner TD, Leiper J, Mitchell JA. Evidence that links loss of cyclooxygenase-2 with increased asymmetric dimethylarginine: novel explanation of cardiovascular side effects associated with anti-inflammatory drugs. Circulation. 2015 Feb 17;131(7):633-42. doi: 10.1161/CIRCULATIONAHA.114.011591. Epub 2014 Dec 9.
- 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.
Jane Mitchell, Professor study director
Imperial College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Celecoxib and L-arginine + celecoxib in people with Healthy, run by Imperial College London at 1 site in United Kingdom.
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 8 inclusion and 9 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 17 Apr 2026. 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 Kingdom. 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Log Reactive Hyperaemic Index (time frame: Baseline and 7 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04765644, which also lists 5 linked publications.
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 17 Apr 2026.