Clinical Trial: Mitochondrial Activity and Myosteatosis in the Cachexia of Cancers of the Upper Aerodigestive Tract

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Mitochondrial Activity and Myosteatosis in the Cachexia of Cancers of the Upper Aerodigestive Tract

Brief Summary:

Loss of muscle mass (scientific term: cachexia) affects about 80% of patients with advanced cancer and impacts their prognosis by decreasing tolerance and response to treatment, decreasing quality of life and survival. The prognosis in these patients depends directly on the importance of the loss of muscle mass. Preserving it is therefore an essential therapeutic objective. It is therefore important to understand perfectly the mechanism of this muscular loss. The accumulation of fat in the muscle (scientific term: myosteatosis) could be a mechanism responsible for this loss of muscle mass. It is indeed a hypothesis proved on animal models. Moreover, it has recently been shown that more the cancer patient loses weight, more his muscle contains fat. This lets think that this deposit of fat in the muscle would be directly related to the loss of muscle mass. All of these observations could not be clearly established in humans and investigators are seeking by this study to illuminate these mechanisms at the human level. A better understanding of these mechanisms would allow investigator to set up targeted treatments against the accumulation of fat in the muscle, which would significantly improve the quality of life of patients with cancer of the aerodigestive pathways and their chances of recovery.

The MYOMEC study includes the inclusion of healthy patients (to form a control group) but also patients with cancer of the upper aero-digestive tract. The study will be divided into two parts: clinical examination and nutritional evaluation the day before surgery at the time of the participants' admission to hospital and then the biological samples during surgery. The nutritional examination consists in collecting the morphological data of the patient, namely:

Its weight, size, calculation of the body mass index Tests of muscular str

Detailed Summary:

Malnutrition is characterized by a negative energy balance due to a deep skeletal muscular loss, which is itself secondary to the reduction of intake and metabolic abnormalities aggravating the loss of weight. Sarcopenia is defined as the loss of muscle mass, the consequences of which are a decrease in muscle strength and physical performance .Cachexia, identified in many chronic diseases (renal insufficiency, heart failure, diabetes, COPD), is the result of an imbalance between proteolysis and proteogenesis and can be defined as a multifactorial syndrome characterized by a weight loss resulting mainly from a loss of lean mass, in particular muscle mass, which is not reversible by an adequate nutritional contribution and which leads to functional abnormalities.

Cancers of the ENT sphere represent about 15% of all cancers in men and 2% in women. They mainly concern subjects between 45 and 70 years of age with a predominant role of ethylo-tobacco poisoning. Patients with upper aero-digestive tract cancers are particularly prone to malnutrition on the part of the tumor itself but also on the context (ethylo-tobacco intoxication, sedentary behavior, poor general condition), tumor localization involving reduction of intake (Mechanical obstruction, anorexia, pain), but also after treatment (chemotherapy, radiotherapy, surgery).

Cancer cachexia affects approximately 80% of patients with advanced cancer and impacts their prognosis by increasing morbidity and mortality, decreased tolerance and response to treatment , decreased quality of life and decreased survival. Its prognosis depends on the extent of the loss of muscle mass. It is generally reported for a patient with a weight loss superior than 5% of its initial weight over the last 6 months, with 3 stages described: Pre-cachexia stage, clean cachexia stage, refractory cachexi
Sponsor: University Hospital, Clermont-Ferrand

Current Primary Outcome: ATP / Oxygen ratio [ Time Frame: at day 1 ]

The ratio of ATP produced by mitochondria and oxygen consumed by muscle mitochondria


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Study of enzymatic mitochondrial activity [ Time Frame: at day 1 ]
    (Expression of cytochrome c oxidase, citrate synthase, HAD, complexes 1, 2 and 3 of the mitochondrial respiratory chain)
  • Study of the activity of muscle lipases [ Time Frame: at day 1 ]
    (Expression of ATGL and HSL)
  • Study of the mobilization of the muscular lipid droplets [ Time Frame: at day 1 ]
    (Expression of the Perilipines 3 and 5)
  • Study of the muscular lipid infiltration [ Time Frame: at day 1 ]
    (Muscular ceramide concentration, DAG and TAG)
  • Study of myosteatosis [ Time Frame: at day 1 ]
    myosteatosis (Computed tomography in L3 for quantification in Hounsfield units)
  • Study of the activity of signaling pathways of protein anabolism [ Time Frame: at day 1 ]
    (phosphorylation rate of mTOR and EiF2alpha)
  • Study of the activity of the signaling pathway of insulin in the muscle [ Time Frame: at day 1 ]
    (AkT phosphorylation rate)
  • Study of muscle proteolytic activity [ Time Frame: at day 1 ]
    (Expression of MURF1 and MAF-box ligases)
  • Evaluation of the preoperative metabolic and nutritional plasma status of patients [ Time Frame: at day 1 ]
    (Insulinemia, Fasting Glycemia, Hepatic and Lipid Assessment, CRP, Albumin, Pre-albumin, Blood Ionogram, Inflammatory Markers)


Original Secondary Outcome: Same as current

Information By: University Hospital, Clermont-Ferrand

Dates:
Date Received: March 31, 2017
Date Started: November 2016
Date Completion: September 2017
Last Updated: April 7, 2017
Last Verified: April 2017