Arginine Supplementation to Improve Cardiovascular and Endothelial Function After NSAID Treatment

NCT04765644 | Completed Phase 4 Results

• 1 other identifier: 18IC4757
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

NSAID; Endothelial function; COX-2; Celecoxib; biomarker

Outcome Measures

Primary Outcomes (2)

• 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

  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.

  Baseline and 7 days

Secondary Outcomes (2)

• Blood Pressure

  Baseline and 7 Days

• Increase/Decrease of Cardiovascular Biomarkers From Baseline

  Baseline and 7 days

Study Arms (2)

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

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

Other: Placebo; Other: L-arginine + placebo

Interventions

Celecoxib DRUG

Two 200 mg capsules per day (400 mg/day) for 7 days

Also known as: Celebrex

Celecoxib

Placebo OTHER

2 capsules/day for 7 days

Placebo

L-arginine + placebo OTHER

L-arginine = Five capsules of 2 mg per day (10 mg/day) for 7 days Placebo = 2 capsules/day for 7 days

Placebo

L-arginine + celecoxib OTHER

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

Celecoxib

Eligibility Criteria

• Age: 18 Years - 40 Years
• Gender Eligibility Details: Male Volunteers
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (1)

Imperial College Clinical Research Facility

London, w12 0HS, United Kingdom

Location

Related Publications (5)

• 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.

  PMID: 23874970 BACKGROUND

• Kirkby 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.

  PMID: 26712011 BACKGROUND

• Warner 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.

  PMID: 18207021 BACKGROUND

• Kirkby 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.

  PMID: 24003163 BACKGROUND

• Ahmetaj-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.

  PMID: 25492024 BACKGROUND

MeSH Terms

Interventions

Celecoxib; Arginine

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential

Results Point of Contact

• Title: Dr Ricky Vaja
• Organization: Imperial College London

r.vaja@imperial.ac.uk

020 7589 5111

Study Officials

• Jane Mitchell, Professor

  Imperial College London

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Healthy male volunteers will be blinded and randomized to 7 days' treatment with celecoxib (200mg bd) or placebo.

Study Record Dates

• First Submitted: February 17, 2021
• First Posted: February 21, 2021
• Study Start: June 10, 2021
• Primary Completion: January 24, 2022
• Study Completion: January 24, 2022
• Last Updated: April 17, 2026
• Results First Posted: October 28, 2024

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)