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

Mitochondrial Dysfunction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02117206
• Other study ID #: 3262
• Status: Completed
• Phase: Phase 4
• First received: March 25, 2014
• Last updated: April 15, 2014
• Start date: November 2005
• Est. completion date: November 2013

Study information

• Verified date: April 2014
• Source: University Hospital, Strasbourg, France
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: ANSM
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: November 2013
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Ischemia
• Mitochondrial Dysfunction
• Severe Lower Limb Ischemia
• Skeletal Muscle Ischemia

Intervention

Drug:
• L-arginine (L-arginine Veyron)

• Nacl

Locations

Country	Name	City	State
France	SERVICE DE PHYSIOLOGIE ET D'EXPLORATIONS FONCTIONNELLES- Nouvel Hôpital Civil, HUS	Strasbourg

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Strasbourg, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Protective effect of L-Arginine on skeletal muscle: V0 and Vmax measurements ACR (Acceptor control ratio)=Vmax/V0		Immediate post surgery muscle biopsy analysis	No
Secondary	Increase walking distance and ankle brachial index		1 month and 3 months after surgery	No