Study of Muscle Wasting Mechanisms and Biomarkers in Hemodialysis Patient
Sponsor study identifier
Secondary identifiers
OTHER · 2008-A00479-46
observational
40
1 country
1
Study Start
July 1, 2009
Actual (reported)Primary Completion
July 31, 2013
Actual (reported)Study Completion
June 28, 2018
Actual (reported)Muscle wasting is present in almost 50% of patients treated with chronic hemodialysis. It is associated with an increased risk of death (particularly from cardiovascular causes) and compromises quality of life (loss of autonomy and fatigue). The mechanisms leading to muscle wasting in chronic kidney disease have been the subject of several studies in animals. These have highlighted the role of the ubiquitin-proteasome system (UPS). Activation of UPS during chronic kidney disease is multifactorial. It is the result of resistance to the action of insulin/IGF1, metabolic acidosis, low grade prolonged inflammation and increased production of myostatin. To date few studies have been conducted in humans. The investigators want to identify blood markers related to muscle protein breakdown in patients undergoing hemodialysis. In parallel, the investigators want to adress the mechanisms involved in muscle proteolysis. In addition, the investigators want to identify the proteins degraded and the ubiquitination enzymes (E2/E3 couples) specifically involved in muscle loss during hemodialysis. Muscle biopsies and blood sample will beperformed during scheduled surgeries in healthy volunteers (negative control), cancer patients (positive control) or undergoing chronic hemodialysis. RNA seq analysis will be performed in blood samples and proteomic mass spectrometry analysis for establishing a specific profile between muscle and blood markers. A limited subset of blood markers common to cancer and hemodialysis atrophying muscles will be used for elaborating a chip dedicated to early detect an atrophying process. Thus, the investigators will first design a diagnostic tool for detecting non-invasively muscle protein breakdown before the onset of muscle atrophy. This will enable early and efficient nutritional counter-measures.
Registry-reported information. Elapsed time and enrollment totals alone do not measure study progress or recruitment pace.
June 28, 2018
Actual (reported)Click on a node to explore related trials.
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Dates and qualifiers reported by the registry. Estimated dates do not confirm that a milestone has occurred.
July 1, 2009
Actual (reported)July 31, 2013
Actual (reported)June 28, 2018
Actual (reported)June 28, 2018
Actual (reported)July 11, 2018
Actual (reported)Transcriptomic analysis of total blood sample
Total RNA will be extracted from blood using Paxgene RNA Extraction kit and analysed by RNAseq and a comparison made between patients and control.
From July 2009 to July 2011
To find biomarkers of muscle atrophy
1. To confirm the implication of UPS in muscular proteolysis of IRCH patients by the detection of an increasing of ARNm, except ubiquitin, implicated in the quantitative RT-PCR system and by the identification of substrates. 2. To locate on the proteins that have to be deteriorated, the sites used by the UPS to fix polyubiquitin chains.
From July 2009 to July 2011
Transcriptomic analysis
From July 2009 to July 2011
Proteomic analysis in muscle biopsies for identification of cachexia mechanism
From July 2009 to July 2011
No intervention
Registry-reported names are shown in full. Names without a link have not yet been matched to a Syfrah profile.
Both female and male participants from18 years old to 75 years old are being studied. Those 40 patients are either affected by cancer or hemodialysis volunteer, or constitute group control.
CHU de Clermont-Ferrand
Clermont-Ferrand, Auvergne, 63003, France
Julien ANIORT
University Hospital, Clermont-Ferrand
40 participants (actual enrollment reported by the registry).
First Submitted
June 28, 2018
First Posted
July 11, 2018
Study Start
July 1, 2009
Actual (reported)Contact the study team to confirm eligibility.
Primary Completion
July 31, 2013
Actual (reported)Study Completion
June 28, 2018
Actual (reported)Last Updated
July 12, 2018
Record last verified: 2018-06
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