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

NCT ID: NCT02117206

Last Updated: 2014-04-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-11-30
• Study Completion Date: 2013-11-30

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.

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.

Conditions

Skeletal Muscle Ischemia; Severe Lower Limb Ischemia; Mitochondrial Dysfunction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

L-Arginine

Femoral arterial infusion of 2 g L-Arginine for 30 min

Group Type: ACTIVE_COMPARATOR

L-arginine (L-arginine Veyron)

Intervention Type: DRUG

Nacl

Femoral arterial infusion of Nacl for 30 min

Group Type: PLACEBO_COMPARATOR

Nacl

Intervention Type: DRUG

Interventions

L-arginine (L-arginine Veyron)

Intervention Type: DRUG

Nacl

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Strasbourg, France

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fabien THAVEAU, MD

Role: PRINCIPAL_INVESTIGATOR

Hôpitaux Universitaires de Strasbourg

Locations

SERVICE DE PHYSIOLOGIE ET D'EXPLORATIONS FONCTIONNELLES- Nouvel Hôpital Civil, HUS

Strasbourg, , France

Countries

France

Other Identifiers

3262

Identifier Type: -

Identifier Source: org_study_id