Clinical trial NCT02117206: Protective Effects of L-arginine During Reperfusion by Femoropopliteal Bypass for Lower Limb Ischemic Syndrome in Humans
Official title: Protective Effects of L-arginine During Reperfusion by Femoropopliteal Bypass for Lower Limb Ischemic Syndrome in Humans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Skeletal Muscle Ischemia
Severe Lower Limb Ischemia
Mitochondrial Dysfunction
Keywords: L-arginine
Lead sponsor: University Hospital, Strasbourg, France
Sponsor class: OTHER
First posted: 2014-04-17
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Protective effect of L-Arginine on skeletal muscle: V0 and Vmax measurements ACR (Acceptor control ratio)=Vmax/V0
timeFrame: Immediate post surgery muscle biopsy analysis
Secondary outcomes:
measure: Increase walking distance and ankle brachial index
timeFrame: 1 month and 3 months after surgery
Other outcomes:
Locations:
city: Strasbourg
country: France
facility: SERVICE DE PHYSIOLOGIE ET D'EXPLORATIONS FONCTIONNELLES- Nouvel Hôpital Civil, HUS
Study officials:
affiliation: Hôpitaux Universitaires de Strasbourg
name: Fabien THAVEAU, MD
role: PRINCIPAL_INVESTIGATOR
References: