Clinical trial NCT00848302: Endothelial Function in Human Arteries
Official title: Endothelial Function in Human Arteries
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Endothelial Dysfunction
Keywords: peripheral vascular disease
endothelial dysfunction
intravascular ultrasound
L-Arginine
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
First posted: 2009-02-20
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Eligibility criteria: 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

Primary outcomes:
measure: IVUS mediated assessment of endothelial-dependent (EDR) and endothelial-independent (EIR) vasorelaxation before and after catheter-directed L-arginine delivery in patent arteries.
timeFrame: Procedural
Secondary outcomes:
measure: Local arterial factors including peripheral L-arginine and nitrotyrosine levels via mass spectrometry and morphologic parameters of plaque composition.
timeFrame: Procedural
Other outcomes:
Locations:
Study officials:
affiliation: Cleveland Clinic Vascular Surgery
name: Vikram Kashyap, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kashyap VS, Lakin RO, Campos P, Allemang M, Kim A, Sarac TP, Hausladen A, Stamler JS. The LargPAD Trial: Phase IIA evaluation of l-arginine infusion in patients with peripheral arterial disease. J Vasc Surg. 2017 Jul;66(1):187-194. doi: 10.1016/j.jvs.2016.12.127. Epub 2017 Mar 30.
citation: Kashyap VS, Lakin RO, Feiten LE, Bishop PD, Sarac TP. In vivo assessment of endothelial function in human lower extremity arteries. J Vasc Surg. 2013 Nov;58(5):1259-66. doi: 10.1016/j.jvs.2013.05.029. Epub 2013 Jul 3.