A randomised controlled trial of oral l-arginine supplementation on platelet and endothelial function and walking distance in patients with peripheral arterial disease - L-ARGININE IN PAD

Status

Active, not recruiting

Phases

Phase 4

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2006-001125-26-GB

Enrollment

Registered

2006-07-23

Start date

2006-08-04

Completion date

Unknown

Last updated

2020-07-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Peripheral arterial disease

Interventions

Product Name: arginine silicate inositol Pharmaceutical Form: Powder for oral solution Pharmaceutical form of the placebo: Powder for oral solution Route of administration of the placebo: Oral use

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: All patients must be able to give informed consent, have an ABPI=65 years) yes F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: Patients with rest pain or ulceration, liver impairment or abnormal platelet count or diabetes and those on clopidogrel, warfarin or non-steroidal anti-inflammatory drugs other than aspirin.

Design outcomes

Primary

Measure	Time frame
Primary end point(s): The primary end-points are platelet and endothelial activity. The method of assessment of these end-points is outlined below: Blood sampling/Assays: 20 mls blood will be taken through a 21 gauge needle from the ante-cubital vein of rested subjects without the use of tourniquet in order to minimise trauma. The first 5ml of blood will be discarded. The following assays and recordings will be performed at baseline, 3 and 6 weeks.. Platelets: Flow cytometry and Ultegra platelet tests will be performed immediately. • Whole blood flow cytometry: Coulter EPICS Flow Cytometer The presence of platelet-monocyte aggregates, expression of P-selectin and fibrinogen binding on platelets will be measured in diluted whole blood samples with and without ex vivo stimulation with ADP, as previously described by our laboratory7. • Rapid platelet function assay: [Ultegra] Platelet aggregation in citrated whole blood samples will be analysed using the ASA and TRAP cartridges12,13. Markers of endothelial activity: The plasma markers of endothelial activity namely vWF, sE-and P-selectin and VCAM-1 have been shown to be elevated in patients with PAD 5,13,15. A reduction in bioavailabilty of nitric oxide may play a role in the increased levels of these markers. In experimental models, nitric oxide has been shown to inhibit secretion of the endothelial Weibel-Palade bodies which store vWF and P-selectin and down regulate VCAM expression of endothelial cells16,17. These adhesive glycoproteins are esssential for platelet adhesion and aggregation and leucocyte rolling16. Inhibition of nitric oxide release in humans has been shown to result in increased levels of vWF18. Shedding of soluble P-selectin by platelets is also inhibited by nitric oxide19. E-selectin is only expressed on activated endothelium and the soluble form which secreted is thus specific for endothelial function. E-selectin expression in vitro is inhibited by nitric oxide20. For the following assa	—

Measure

Time frame

Primary end point(s): The primary end-points are platelet and endothelial activity. The method of assessment of these end-points is outlined below: Blood sampling/Assays: 20 mls blood will be taken through a 21 gauge needle from the ante-cubital vein of rested subjects without the use of tourniquet in order to minimise trauma. The first 5ml of blood will be discarded. The following assays and recordings will be performed at baseline, 3 and 6 weeks.. Platelets: Flow cytometry and Ultegra platelet tests will be performed immediately. • Whole blood flow cytometry: Coulter EPICS Flow Cytometer The presence of platelet-monocyte aggregates, expression of P-selectin and fibrinogen binding on platelets will be measured in diluted whole blood samples with and without ex vivo stimulation with ADP, as previously described by our laboratory7. • Rapid platelet function assay: [Ultegra] Platelet aggregation in citrated whole blood samples will be analysed using the ASA and TRAP cartridges12,13. Markers of endothelial activity: The plasma markers of endothelial activity namely vWF, sE-and P-selectin and VCAM-1 have been shown to be elevated in patients with PAD 5,13,15. A reduction in bioavailabilty of nitric oxide may play a role in the increased levels of these markers. In experimental models, nitric oxide has been shown to inhibit secretion of the endothelial Weibel-Palade bodies which store vWF and P-selectin and down regulate VCAM expression of endothelial cells16,17. These adhesive glycoproteins are esssential for platelet adhesion and aggregation and leucocyte rolling16. Inhibition of nitric oxide release in humans has been shown to result in increased levels of vWF18. Shedding of soluble P-selectin by platelets is also inhibited by nitric oxide19. E-selectin is only expressed on activated endothelium and the soluble form which secreted is thus specific for endothelial function. E-selectin expression in vitro is inhibited by nitric oxide20. For the following assa

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Countries

United Kingdom

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026