Severe Chronic Respiratory Failure and Citrulline

Denutrition in patients with COPD (Chronic Obstructive Pulmonary Disease) is characterized by muscle atrophy and loss of strength in the lower extremities. It worsens the symptomatology, exercise intolerance, impaired quality of life and prognosis of patients. Consequence of a protein deficiency associated with systemic inflammation, denutrition is becoming increasingly important in patients with chronic respiratory failure (CRF). L-citrulline is an amino acid having a direct action on muscle protein synthesis. The citrulline supplementation is an effective treatment to fight against muscle loss in aging subjects. Its impact on the functional and nutritional status of COPD patients has not been studied. Our main objective is to determine the impact of supplementation with Citrulline on mass and peripheral muscle strength in COPD with CRF. Our secondary objectives are to identify whether these benefits are dependent on the severity of the disease and if they are associated with increased physical activity, exercise tolerance and an improvement in symptoms and quality of life. This prospective, randomized, controlled, double-blind study will include 60 stable COPD patients (stage 3 and 4), with long-term oxygen therapy and / or non-invasive ventilation, BMI \<25 kg.m2 and suspicion of sarcopenia. For 45 days, patients will receive either citrulline (ProteoCIT®, 10mg) or placebo. The severity of COPD will be assessed by spirometry and blood gas data, the BODE index, exacerbations, comorbidities, nutritional status and systemic inflammation (CRPs, Fibrinogens). the investigators will evaluate before and after supplementation: body composition (DEXA), quadriceps strength and grip strength, walking speed, the exercise tolerance (6MWD), dyspnea (MMRC scales, BDI / TDI), quality of life (CAT and VSRQ questionnaires). Physical activity will be assessed by continuous actigraphy. This multicenter study will be conducted in 3 French hospitals: Grenoble, Nancy, Dijon.