Arginine Supplementation to Improve Cardiovascular and Endothelial Function After NSAID Treatment (ASCENT)

Imperial College London

Status and phase: Completed; Phase 4

Conditions: Healthy

Treatments: Other: Placebo; Other: L-arginine + celecoxib; Other: L-arginine + placebo; Drug: Celecoxib

Study type: Interventional

Funder types: Other

Identifiers

NCT04765644

18IC4757

Details and patient eligibility

About

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.

Full 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.

Enrollment: 44 patients

Sex: Male

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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44 participants in 2 patient groups, including a placebo group

Celecoxib

Active Comparator group

Description:

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

Treatment:

Drug: Celecoxib

Other: L-arginine + celecoxib

Placebo

Placebo Comparator group

Description:

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

Treatment:

Other: L-arginine + placebo

Other: Placebo