Endothelial Function in Human Arteries

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00848302
Recruitment Status : Completed
First Posted : February 20, 2009
Last Update Posted : March 7, 2017
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Endothelial Dysfunction Drug: L-arginine Early Phase 1

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Endothelial Function in Human Arteries
Study Start Date : September 2009
Actual Primary Completion Date : January 2011
Actual Study Completion Date : January 2011

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: L-arginine
Assess the effects of regional L-arginine supplementation in patients with chronic lower extremity occlusive disease undergoing angiography
Drug: L-arginine
30 patients will receive either 50, 100 or 500mg L-arginine supplementation infused via a end-hole catheter
Other Name: Nitric oxide

Primary Outcome Measures :
  1. IVUS mediated assessment of endothelial-dependent (EDR) and endothelial-independent (EIR) vasorelaxation before and after catheter-directed L-arginine delivery in patent arteries. [ Time Frame: Procedural ]

Secondary Outcome Measures :
  1. Local arterial factors including peripheral L-arginine and nitrotyrosine levels via mass spectrometry and morphologic parameters of plaque composition. [ Time Frame: Procedural ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00848302

Sponsors and Collaborators
The Cleveland Clinic
Principal Investigator: Vikram Kashyap, MD Cleveland Clinic Vascular Surgery

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: The Cleveland Clinic Identifier: NCT00848302     History of Changes
Other Study ID Numbers: K23HLOBO247
K23HLOBO247 ( Other Identifier: National Heart Lung Blood Institute )
First Posted: February 20, 2009    Key Record Dates
Last Update Posted: March 7, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by The Cleveland Clinic:
peripheral vascular disease
endothelial dysfunction
intravascular ultrasound

Additional relevant MeSH terms:
Nitric Oxide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Free Radical Scavengers
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Protective Agents