Protective Effects of L-arginine During Reperfusion by Femoropopliteal Bypass for Lower Limb Ischemic Syndrome in Humans
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Protective effect of L-Arginine on skeletal muscle: V0 and Vmax measurements ACR (Acceptor control ratio)=Vmax/V0
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •atherosclerotic patient with peripheral arterial disease stage 2-4 Leriche and Fontaine classification
- •requiring surgical revascularization by femoropopliteal bypass
- •above 18 years old
排除标准
- •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
研究组 & 干预措施
L-Arginine
Femoral arterial infusion of 2 g L-Arginine for 30 min
干预措施: L-arginine (L-arginine Veyron) (Drug)
Nacl
Femoral arterial infusion of Nacl for 30 min
干预措施: Nacl (Drug)
结局指标
主要结局
Protective effect of L-Arginine on skeletal muscle: V0 and Vmax measurements ACR (Acceptor control ratio)=Vmax/V0
时间窗: Immediate post surgery muscle biopsy analysis
次要结局
- Increase walking distance and ankle brachial index(1 month and 3 months after surgery)