Muscle Atrophy in Lung Cancer and Hemodialysed PatientsNCT03583177
Muscle Wasting in Hemodialysis Patient
An observational study of Muscle Atrophy in Lung Cancer and Hemodialysed Patients, run by University Hospital, Clermont-Ferrand at 1 site in France.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Muscle Atrophy in Lung Cancer and Hemodialysed Patients
- How many people
- 40 participants
- Where
- 1 siteFrance
- Study dates
- 1 Jul 2009to 28 Jun 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Study of Muscle Wasting Mechanisms and Biomarkers in Hemodialysis Patient
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.
Read more
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.
Read the detailed description
Hypothesis Measuring urinary 3-methylhistidine is a simple tool to assess proteolysis in clinical practice. However it is not totally specific of muscle proteolysis because it may reflect an intestinal catabolism. Moreover, its dosage cannot be used in patients with renal impairment especially in case of anuria. Apart from achieving muscle biopsy or measuring the overall kinetics of proteins it does not yet exist simple and reproducible diagnostic tool for measuring muscle proteolysis. With the present study, the investigators expect to identify in the blood of patients a particular transcriptomic profile related to the activation of muscle proteolysis, including increased proinflammatory cytokine transcripts.
Rodent models of CKD were used to identify major proteolytic system and signal pathway implicated in muscle wasting caused by uremia. These finding needs to be confirmed in humans studies. Also, other actors of muscle atrophy could be identified in humans. Notably, so far, few studies have been performed in order to determine which E2 are involved in muscle atrophy, and to knowledge of the investigators no one in CKD. Finally, data on muscle proteasome substrates are limited since only actin was clearly identified in humans by the team. The investigators expect an activation of the proteasome system with an increase in the expression of enzymes E2s, E3s including MURF1 and MAFbx and proteasome subunit in patients treated with hemodialysis. The investigators could also observe an activation of caspase system which is thought to work in concert with the UPS.
Materials and methods 2.1. Population The experiments will be performed using blood sample and human muscle biopsies obtained during programmed orthopedic surgery (negative control), cancer (positive control) and hemodialysis patients. This translational research program has already been accepted (DGS 2008-A00479-46) and inclusion of patients already started. A maximum of 15 patients per group will be included. Inclusion and exclusion criteria were set-up according to the objectives (absence of any pathology for controls, etc.) and the legislation (written consent, etc.). Thirty-two patients have already been included so far, and biopsies are stored in liquid nitrogen. Blood samples are collected just before surgery using Paxgene RNA tubes and stored following the manufacturer's instructions until analysis.
2.2. Blood sample Total RNA will be extracted from blood using Paxgene RNA Extraction kit and analysed by RNAseq 2.3. Muscle biopsies 2.3.1. Transcriptomic analysis Total RNA will be extracted from human muscle biopsies using commercial kits. The investigators will first verify that known muscles markers are up-regulated in cancer patient biopsies (positive controls) and address their levels in muscle biopsies from hemodialysis patients. We will thus perform qRT-PCR UBE2B, UBE2D2, MaFbx, MuRF1, Ozz, ASB2, E4B, Nedd4, Mdm2 and 26S proteasome subunits.
2.3.2. Proteomic analysis Proteomic analysis will be performed usin shot gun spectrometry analysis
- Being tested
- No intervention
- Keywords
- Proteolysis, Muscle, Cachexia
- Medical subject headings
- Cachexia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No interventionDiagnostic test
No intervention
| Study group | Role | What they receive |
|---|---|---|
| healthy volunteers | Not described Receives: Diagnostic Test: No intervention | |
| cancer patients | Not described Receives: Diagnostic Test: No intervention | |
| undergoing chronic hemodialysis patients | Not described Receives: Diagnostic Test: No intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From July 2009 to July 2011
To find biomarkers of muscle atrophy
- 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.
- To locate on the proteins that have to be deteriorated, the sites used by the UPS to fix polyubiquitin chains.
Measured: From July 2009 to July 2011
Secondary outcomes (2)
Transcriptomic analysis
Total RNA will be extracted from human muscle biopsies using commercial kits. We will first verify that known muscles markers are up-regulated in cancer patient biopsies (positive controls) and address their levels in muscle biopsies from hemodialysis patients. We will thus perform qRT-PCR UBE2B, UBE2D2, MaFbx, MuRF1, Ozz, ASB2, E4B, Nedd4, Mdm2 and 26S proteasome subunits.
Measured: From July 2009 to July 2011
Proteomic analysis in muscle biopsies for identification of cachexia mechanism
Proteomic analysis will be performed usin shot gun spectrometry analysis
Measured: From July 2009 to July 2011
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2018
- Study start1 Jul 2009
- Primary completion31 Jul 2013
- Study completion28 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Muscle Atrophy in Lung Cancer and Hemodialysed PatientsStudies of the same condition, open and under way.
- More trials run by University Hospital, Clermont-FerrandThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Clermont-Ferrand
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Julien ANIORT, Principal investigator, University Hospital, Clermont-Ferrand
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03583177
- Sponsor's protocol ID
- CHU-397
- Other IDs
- 2008-A00479-46
- Status last verified
- Jun 2018
- First submitted
- 28 Jun 2018
- Last updated
- 12 Jul 2018
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Muscle Wasting Mechanisms and Biomarkers in Hemodialysis Patient
- ClinicalTrials.gov ID
- NCT03583177
- Acronym / sponsor ID
- CHU-397
- Keywords
- Proteolysis, Muscle, Cachexia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- University Hospital, Clermont-FerrandUniversity, hospital or other
- Study start
- 1 Jul 2009 (actual)
- Primary completion
- 31 Jul 2013 (actual)
- Study completion
- 28 Jun 2018 (actual)
- First posted
- 11 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Hypothesis Measuring urinary 3-methylhistidine is a simple tool to assess proteolysis in clinical practice. However it is not totally specific of muscle proteolysis because it may reflect an intestinal catabolism. Moreover, its dosage cannot be used in patients with renal impairment especially in case of anuria. Apart from achieving muscle biopsy or measuring the overall kinetics of proteins it does not yet exist simple and reproducible diagnostic tool for measuring muscle proteolysis. With the present study, the investigators expect to identify in the blood of patients a particular transcriptomic profile related to the activation of muscle proteolysis, including increased proinflammatory cytokine transcripts.
Rodent models of CKD were used to identify major proteolytic system and signal pathway implicated in muscle wasting caused by uremia. These finding needs to be confirmed in humans studies. Also, other actors of muscle atrophy could be identified in humans. Notably, so far, few studies have been performed in order to determine which E2 are involved in muscle atrophy, and to knowledge of the investigators no one in CKD. Finally, data on muscle proteasome substrates are limited since only actin was clearly identified in humans by the team. The investigators expect an activation of the proteasome system with an increase in the expression of enzymes E2s, E3s including MURF1 and MAFbx and proteasome subunit in patients treated with hemodialysis. The investigators could also observe an activation of caspase system which is thought to work in concert with the UPS.
Materials and methods 2.1. Population The experiments will be performed using blood sample and human muscle biopsies obtained during programmed orthopedic surgery (negative control), cancer (positive control) and hemodialysis patients. This translational research program has already been accepted (DGS 2008-A00479-46) and inclusion of patients already started. A maximum of 15 patients per group will be included. Inclusion and exclusion criteria were set-up according to the objectives (absence of any pathology for controls, etc.) and the legislation (written consent, etc.). Thirty-two patients have already been included so far, and biopsies are stored in liquid nitrogen. Blood samples are collected just before surgery using Paxgene RNA tubes and stored following the manufacturer's instructions until analysis.
2.2. Blood sample Total RNA will be extracted from blood using Paxgene RNA Extraction kit and analysed by RNAseq 2.3. Muscle biopsies 2.3.1. Transcriptomic analysis Total RNA will be extracted from human muscle biopsies using commercial kits. The investigators will first verify that known muscles markers are up-regulated in cancer patient biopsies (positive controls) and address their levels in muscle biopsies from hemodialysis patients. We will thus perform qRT-PCR UBE2B, UBE2D2, MaFbx, MuRF1, Ozz, ASB2, E4B, Nedd4, Mdm2 and 26S proteasome subunits.
2.3.2. Proteomic analysis Proteomic analysis will be performed usin shot gun spectrometry analysis
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| healthy volunteers | – | Diagnostic Test: No intervention |
| cancer patients | – | Diagnostic Test: No intervention |
| undergoing chronic hemodialysis patients | – | Diagnostic Test: No intervention |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (7 listed)
- acute or chronic infections,
- diabetes mellitus,
- corticosteroid or hormone therapy or
- pregnancy.
- Glomerular filtration rate < 90 mL/min for LC and CT patients
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| No interventionNo intervention | Diagnostic test | cancer patients, healthy volunteers, undergoing chronic hemodialysis patients |
Primary outcome
Transcriptomic analysis of total blood sample
Time frame: From July 2009 to July 2011
Total RNA will be extracted from blood using Paxgene RNA Extraction kit and analysed by RNAseq and a comparison made between patients and control.
To find biomarkers of muscle atrophy
Time frame: From July 2009 to July 2011
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.
2 secondary outcomes
Transcriptomic analysis
Time frame: From July 2009 to July 2011
Proteomic analysis in muscle biopsies for identification of cachexia mechanism
Time frame: From July 2009 to July 2011
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2018.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julien ANIORT principal investigator
University Hospital, Clermont-Ferrand
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Muscle Atrophy in Lung Cancer and Hemodialysed Patients, run by University Hospital, Clermont-Ferrand at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Transcriptomic analysis of total blood sample (time frame: From July 2009 to July 2011). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2018.