Arginine Supplementation to Improve Cardiovascular and Endothelial Function After NSAID Treatment

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.

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