Endothelial Function in Human Arteries

Early Phase 1

Completed

• Conditions: Endothelial Dysfunction
• Interventions: Drug: L-arginine

• Registration Number: NCT00848302
• Lead Sponsor: The Cleveland Clinic

Brief Summary

Up to 30 patients with lower extremity disease scheduled to undergo diagnostic angiography will undergo baseline bloodwork and IVUS (intravascular ultrasound), followed by dosing with L-arginine to assess changes in endothelial function.

Detailed Description

We will assess doses of regional L-arginine supplementation in patients undergoing elective angiography for lower extremity PAD. Assessment of EDR and EIR with IVUS in patent arteries will be performed with one of 3 doses of catheter-directed L-arginine. We will obtain plasma samples from the peripheral arteries and assay amino acid levels and protein oxidation products using mass spectrometry. These experiments will determine the optimal L-arginine supplementation dose to be used in further studies. We expect to show that L-arginine supplementation will have a more significant effect on vessels less affected by atherosclerosis, but that this effect diminishes with greater atheroma accumulation as measured by IVUS virtual histology. Also, we expect L-arginine supplementation to be most effective in vessels with low baseline L-arginine levels. Lastly, we will compare local arterial factors obtained via catheter-directed arterial sampling (NOx, L-arginine, nitrotyrosine levels) to traditional serum risk factors (glucose, HbA1c, LDL, homocysteine and hs C-reactive protein).

Study Timeline

• Study First Submitted: 2009-02-12
• Study First Submitted QC: 2009-02-19
• Study First Posted: 2009-02-20
• Study Start: 2009-09
• Primary Completion: 2011-01
• Study Completion: 2011-01
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-06
• Last Update Posted: 2017-03-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

• age >18 years
• symptoms of intermittent claudication, rest pain or minor tissue loss (Rutherford Category I-V)
• ABI of <.90
• angiographic demonstration of a 100mm patent segment of superficial femoral artery containing at least one distal runoff vessel

Exclusion Criteria

• acute limb ischemia,
• contraindication to angiography (creatinine >2.5)
• concurrent oral anticoagulant therapy that cannot be safely withheld
• extensive tissue loss or gangrene

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
L-arginine	L-arginine	Assess the effects of regional L-arginine supplementation in patients with chronic lower extremity occlusive disease undergoing angiography

Primary Outcome Measures

Name	Time	Method
IVUS mediated assessment of endothelial-dependent (EDR) and endothelial-independent (EIR) vasorelaxation before and after catheter-directed L-arginine delivery in patent arteries.	Procedural

Secondary Outcome Measures

Name	Time	Method
Local arterial factors including peripheral L-arginine and nitrotyrosine levels via mass spectrometry and morphologic parameters of plaque composition.	Procedural