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Protective Effects of L-arginine During Reperfusion by Femoropopliteal Bypass for Lower Limb Ischemic Syndrome in Humans

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: NCT02117206
Recruitment Status : Completed
First Posted : April 17, 2014
Last Update Posted : April 17, 2014
Information provided by (Responsible Party):
University Hospital, Strasbourg, France

Brief Summary:

The symptoms and severity of arterial disease is secondary to perfusion deficit. The specific alteration of the mitochondrial function of ischemic skeletal muscle plays an important role, and therapeutic enhancing mitochondrial function are associated with a clinical improvement with increase in the walking distance of the patient.

In severe ischemia, reperfusion required is accompanied by a deleterious episode through a worsening of endothelial dysfunction (impaired pathway of nitric oxide (NO)), majorant alteration of cellular energy and the hormonal and inflammatory responses. This is reperfusion syndrome, which can lead to grave consequences. Our goal is to limit mitochondrial and endothelial dysfunction (increased by the reperfusion) by stimulating the NO pathway by in situ addition of its precursor, L-arginine. Our working hypothesis is that this cellular improvement will be accompanied by an increase in systolic pressure index and an improvement in the walking distance.

Method: This is a trial with direct individual benefit, comparative, randomized, prospective, single-center, double-blind, versus placebo.

Condition or disease Intervention/treatment Phase
Skeletal Muscle Ischemia Severe Lower Limb Ischemia Mitochondrial Dysfunction Drug: L-arginine (L-arginine Veyron) Drug: Nacl Phase 4

Detailed Description:

2 groups of 30 patients with severe lower limb ischemia requiring femoropopliteal bypass revascularization participate in the study. The control group (placebo isoosmotic saline) will be compared to the treated group (femoral arterial infusion of 2 g L-Arginine for 30 min).

Heart rate, blood pressure and body temperature will be monitored continuously. The gastrocnemius muscle is biopsied before and 30 minutes after revascularization to analyze mitochondrial respiration and its control. Both femoral and brachial concomitant venous samples will judge the importance of muscle damage (lactate, muscle enzymes) and released mediators (cytokines, NO and endothelin) on the local and general.

Main clinical implications: L-arginine supplementation in atherosclerotic patients requiring femoropopliteal bypass to limit the initial deleterious effects of reperfusion and improve their walking distance and therefore their quality of life. Then extending this treatment to other patients with peripheral arterial disease.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: Protective Effects of L-arginine During Reperfusion by Femoropopliteal Bypass for Lower Limb Ischemic Syndrome in Humans
Study Start Date : November 2005
Actual Primary Completion Date : March 2012
Actual Study Completion Date : November 2013

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: L-Arginine
Femoral arterial infusion of 2 g L-Arginine for 30 min
Drug: L-arginine (L-arginine Veyron)
Placebo Comparator: Nacl
Femoral arterial infusion of Nacl for 30 min
Drug: Nacl

Primary Outcome Measures :
  1. Protective effect of L-Arginine on skeletal muscle: V0 and Vmax measurements ACR (Acceptor control ratio)=Vmax/V0 [ Time Frame: Immediate post surgery muscle biopsy analysis ]

Secondary Outcome Measures :
  1. Increase walking distance and ankle brachial index [ Time Frame: 1 month and 3 months after surgery ]

Information from the National Library of Medicine

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

Inclusion Criteria:

  • atherosclerotic patient with peripheral arterial disease stage 2-4 Leriche and Fontaine classification
  • requiring surgical revascularization by femoropopliteal bypass
  • above 18 years old

Exclusion Criteria:

  • active infectious disease
  • severe heart disease
  • chronic renal insufficency
  • pregnant women
  • women of childbearing age and with no effective contraception for at least three months

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): NCT02117206

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Strasbourg, France, 67091
Sponsors and Collaborators
University Hospital, Strasbourg, France
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Principal Investigator: Fabien THAVEAU, MD Hôpitaux Universitaires de Strasbourg

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Responsible Party: University Hospital, Strasbourg, France Identifier: NCT02117206    
Other Study ID Numbers: 3262
First Posted: April 17, 2014    Key Record Dates
Last Update Posted: April 17, 2014
Last Verified: April 2014
Keywords provided by University Hospital, Strasbourg, France:
Additional relevant MeSH terms:
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Pathologic Processes