NCT03583177

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at P25-P50 for all trials

Timeline
Completed

Started Jul 2009

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2009

Completed
4.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 31, 2013

Completed
4.9 years until next milestone

First Submitted

Initial submission to the registry

June 28, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 28, 2018

Completed
13 days until next milestone

First Posted

Study publicly available on registry

July 11, 2018

Completed
Last Updated

July 12, 2018

Status Verified

June 1, 2018

Enrollment Period

4.1 years

First QC Date

June 28, 2018

Last Update Submit

July 11, 2018

Conditions

Keywords

ProteolysisMuscleCachexia

Outcome Measures

Primary Outcomes (2)

  • 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

Secondary Outcomes (2)

  • Transcriptomic analysis

    From July 2009 to July 2011

  • Proteomic analysis in muscle biopsies for identification of cachexia mechanism

    From July 2009 to July 2011

Study Arms (3)

healthy volunteers

Diagnostic Test: No intervention

cancer patients

Diagnostic Test: No intervention

undergoing chronic hemodialysis patients

Diagnostic Test: No intervention

Interventions

No interventionDIAGNOSTIC_TEST

No intervention

cancer patientshealthy volunteersundergoing chronic hemodialysis patients

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

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.

You may qualify if:

  • over 18 years old,
  • with either newly diagnosed lung cancer (for whom surgical resection was programmed by thoracotomy) or patients with end-stage renal failure treated for at least 6 months by hemodialysis and necessitating femoral bypass revascularization.
  • The control group patients required hip replacement for osteoarthritis.

You may not qualify if:

  • acute or chronic infections,
  • diabetes mellitus,
  • corticosteroid or hormone therapy or
  • pregnancy.
  • Glomerular filtration rate \< 90 mL/min for LC and CT patients
  • active neoplasia in patients of the HD and CT groups
  • CRP \> 3 mg/L in for CT patients

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

CHU de Clermont-Ferrand

Clermont-Ferrand, Auvergne, 63003, France

Location

MeSH Terms

Conditions

Cachexia

Condition Hierarchy (Ancestors)

Weight LossBody Weight ChangesBody WeightSigns and SymptomsPathological Conditions, Signs and SymptomsThinness

Study Officials

  • Julien ANIORT

    University Hospital, Clermont-Ferrand

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
CROSS SECTIONAL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 28, 2018

First Posted

July 11, 2018

Study Start

July 1, 2009

Primary Completion

July 31, 2013

Study Completion

June 28, 2018

Last Updated

July 12, 2018

Record last verified: 2018-06

Locations