Plain English Summary
Background and study aims
The aim of this study is to use a technique called quantitative magnetic resonance imaging (MRI) to measure the iron content of the liver, spleen, heart and pancreas and also liver fat fraction of patients who are undergoing hemodialysis or peritoneal dialysis, at the start of dialysis and thereafter when they are being treated with intravenous iron and erythropoiesis stimulating agents (ESA). The study will also find out about the risk factors of iron overload, and especially the role of iron therapy.
Who can participate?
Patients undergoing hemodialysis three times a week, home hemodialysis or peritoneal dialysis at the initiation of the technique and thereafter
What does the study involve?
MRI is used to determine the iron content of the participants' liver, spleen, heart, pancreas and also liver fat fraction. The participants' medical records and dialysis charts are reviewed by clinical research technicians. Blood samples are taken and the patients are tested for measurement of biochemical markers of iron metabolism and for a genetic defect of the HFE genes. A test is carried out to determine the participants' alcohol consumption and to detect alcohol addiction. Patients are followed up for analysis of relevant clinical events (illness and death).
What are the possible benefits and risks of participating?
Careful monitoring of iron therapy will allow the safe use of intravenous iron, avoiding iron overload. The risks of participating are anxiety related to MRI exams and genetic testing.
Where is the study run from?
Hôpital Privé Claude Galien (Quincy sous Sénart), Centre Hospitalier Marc Jacquet (Melun), Groupe Hospitalier Pitié Salpêtrière (Paris), Groupe Hospitalier Kremlin Bicêtre (Kremlin Bicêtre), Centre Nephrocare (Marne la Vallée), Polyclinique des Mousseaux (Evry), Clinique du Landy (St Ouen), Polyclinique les Fleurs (Ollioules), CHU Brabois (Nancy), Clinique Sainte Anne (Strasbourg), CH (Mulhouse), Hôpital Jean Mermoz (Lyon), Polyclinique du Plateau (Bezons)
When is the study starting and how long is it expected to run for?
January 2005 to January 2035
Who is funding the study?
The Physicians' Association of Claude Galien Hospital (Association Quincy Recherche Clinique et Thérapeutique) (France)
Who is the main contact?
Dr Guy Rostoker
rostotom@orange.fr
Trial website
Contact information
Type
Scientific
Primary contact
Dr Guy Rostoker
ORCID ID
http://orcid.org/0000-0002-4383-3825
Contact details
Service de Néphrologie et de Dialyse
Hopital Privé Claude Galien
20 route de Boussy
Quincy Sous Senart
91480
France
-
rostotom@orange.fr
Type
Scientific
Additional contact
Ms Mireille Griuncelli
ORCID ID
Contact details
Service de Néphrologie et de Dialyse
Hôpital Privé Claude Galien
20 route de Boussy
Quincy-sous-Sénart
91480
France
-
rostotom@orange.fr
Type
Scientific
Additional contact
Ms Christelle Loridon
ORCID ID
Contact details
Service de Néphrologie et de Dialyse
Hôpital Privé Claude Galien
20 route de Boussy
Quincy-sous-Sénart
91480
France
-
rostotom@orange.fr
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Analysis of hepatic iron stores of haemodialysis patients by magnetic resonance imaging: a cross-sectional and longitudinal study
Acronym
Study hypothesis
The aim of this study was to determine hepatic iron content, using magnetic resonance imaging (MRI) and the Rennes University algorithm, in a cohort of haemodialysis patients receiving both intravenous iron and erythropoiesis stimulating agents (ESA), in keeping with current guidelines.
Ethics approval
1. COMEDIMS (Drug, Devices and Clinical Trials Committee) CHP Claude Galien, 09/12/2004, ref: 2004-2
2. COMEDIMS (Drug, Devices and Clinical Trials Committee) CHP Claude Galien, 15/02/2013, ref 2013-2
Study design
Prospective cross-sectional longitudinal multicenter study
Primary study design
Observational
Secondary study design
Cross-sectional longitudinal study
Trial setting
Hospitals
Trial type
Diagnostic
Patient information sheet
Not available in web format, please contact rostotom@orange.fr to request a patient information sheet
Condition
Chronic kidney disease
Intervention
Current interventions as of 08/09/2016:
1. Non-randomised measurement of hepatic iron content by means of T1 and T2 contrast magnetic resonance imaging (MRI) on a Sigma MRI unit (GE Medical Systems, Milwaukee, WI, USA) operating at a field strength of 1.5 Tesla
2. Five weighted gradient-recalled-echo sequences of the liver (GRE T1, DP, T2, T2+ and T2++) with a repetition time of 120 ms will be acquired
3. Measurements will be made in five regions of interest larger than 1 cm2 (usually 3 on the right liver and 2 on paraspinal muscles on the same slice), and calculated the liver-to-muscle ratio
4. Areas of cyst-free liver will be examined in patients with renal and hepatic polycystosis
5. We will used the software algorithm provided by Rennes University (http://www.radio.univ-rennes1.fr) to determine hepatic iron content (expressed in micromol/g of dry liver)
6. Duration of MRI examination is about 20 minutes
7. Measurements of biochemical markers of iron metabolism:
7.1. Serum ferritin
7.2. Serum iron
7.3. Transferrin
7.4. Transferrin saturation (TSAT)
7.5. Soluble transferrin receptors (sTfR)
7.6. Serum hepcidin-25
7.7. Screening for the C282Y HFE gene mutation
7.8. Serum hepcidin-20, 22, and 24
7.9. Serum erythroferrone
7.10. Serum glycosylated ferritin
7.11. Serum non bound transferrin iron (NBTI) and serum labile iron
7.12. Plasma FGF23 C-terminal, plasma FGF23 Intact, soluble alpha Klotho, sclerotin
8. Use of The Alcohol Use Disorder Identification Test (AUDIT) to quantify alcohol consumption and to detect addiction
9. Measurement of iron content in spleen and heart will be performed simultaneously to determination of liver iron content by R2* relaxometry
10. Follow-up of patients for relevant clinical events (morbidity and mortality)
Added 23/10/2018: Measurement of liver fat fraction by R2* relaxometry with IDEAL IQ algorithm and Rennes University Gandon’s algorithm and measurement of iron content in pancreas by R2* relaxometry
Previous interventions from 01/03/2013 to 08/09/2016:
1. Non-randomised measurement of hepatic iron content by means of T1 and T2 contrast magnetic resonance imaging (MRI) on a Sigma MRI unit (GE Medical Systems, Milwaukee, WI, USA) operating at a field strength of 1.5 Tesla
2. Five weighted gradient-recalled-echo sequences of the liver (GRE T1, DP, T2, T2+ and T2++) with a repetition time of 120 ms will be acquired
3. Measurements will be made in five regions of interest larger than 1 cm2 (usually 3 on the right liver and 2 on paraspinal muscles on the same slice), and calculated the liver-to-muscle ratio
4. Areas of cyst-free liver will be examined in patients with renal and hepatic polycystosis
5. We will used the software algorithm provided by Rennes University (http://www.radio.univ-rennes1.fr) to determine hepatic iron content (expressed in micromol/g of dry liver)
6. Duration of MRI examination is about 20 minutes
7. Measurements of biochemical markers of iron metabolism:
7.1. Serum ferritin
7.2. Serum iron
7.3. Transferrin
7.4. Transferrin saturation (TSAT)
7.5. Soluble transferrin receptors (sTfR)
7.6. Serum hepcidin-25
7.7. Screening for the C282Y HFE gene mutation
8. Use of The Alcohol Use Disorder Identification Test (AUDIT) to quantify alcohol consumption and to detect addiction
9. Measurement of iron content in spleen and heart will be performed simultaneously to determination of liver iron content by R2* relaxometry
10. Follow-up of patients for relevant clinical events (morbidity and mortality)
Previous interventions from 07/12/2012 to 01/03/2013:
1. Non-randomised measurement of hepatic iron content by means of T1 and T2 contrast magnetic resonance imaging (MRI) on a Sigma MRI unit (GE Medical Systems, Milwaukee, WI, USA) operating at a field strength of 1.5 Tesla
2. Five weighted gradient-recalled-echo sequences of the liver (GRE T1, DP, T2, T2+ and T2++) with a repetition time of 120 ms will be acquired
3. Measurements will be made in five regions of interest larger than 1 cm2 (usually 3 on the right liver and 2 on paraspinal muscles on the same slice), and calculated the liver-to-muscle ratio
4. Areas of cyst-free liver will be examined in patients with renal and hepatic polycystosis
5. We will used the software algorithm provided by Rennes University (http://www.radio.univ-rennes1.fr) to determine hepatic iron content (expressed in micromol/g of dry liver)
6. Duration of MRI examination is about 20 minutes
7. Measurements of biochemical markers of iron metabolism:
7.1. Serum ferritin
7.2. Serum iron
7.3. Transferrin
7.4. Transferrin saturation (TSAT)
7.5. Soluble transferrin receptors (sTfR)
7.6. Serum hepcidin-25
7.7. Screening for the C282Y HFE gene mutation
8. Use of The Alcohol Use Disorder Identification Test (AUDIT) to quantify alcohol consumption and to detect addiction
9. Measurement of iron content in spleen and heart will be performed simultaneously to determination of liver iron content by T2*/R2* sequences
Previous interventions until 07/12/2012:
1. Non-randomised measurement of hepatic iron content by means of T1 and T2 contrast magnetic resonance imaging (MRI) on a Sigma MRI unit (GE Medical Systems, Milwaukee, WI, USA) operating at a field strength of 1.5 Tesla
2. Five weighted gradient-recalled-echo sequences of the liver (GRE T1, DP, T2, T2+ and T2++) with a repetition time of 120 ms will be acquired
3. Measurements will be made in five regions of interest larger than 1 cm2 (usually 3 on the right liver and 2 on paraspinal muscles on the same slice), and calculated the liver-to-muscle ratio
4. Areas of cyst-free liver will be examined in patients with renal and hepatic polycystosis
5. We will used the software algorithm provided by Rennes University (http://www.radio.univ-rennes1.fr) to determine hepatic iron content (expressed in micromol/g of dry liver)
6. Duration of MRI examination is about 20 minutes
7. Measurements of biochemical markers of iron metabolism:
7.1. Serum ferritin
7.2. Serum iron
7.3. Transferrin
7.4. Transferrin saturation (TSAT)
7.5. Soluble transferrin receptors (sTfR)
7.6. Serum hepcidin-25
7.7. Screening for the C282Y HFE gene mutation
8. Use of The Alcohol Use Disorder Identification Test (AUDIT) to quantify alcohol consumption and to detect addiction
Intervention type
Other
Phase
Not Applicable
Drug names
Primary outcome measure
1. Determination of iron content (micromol/g/dry weight)
2. Percentage of patients with abnormal iron liver content (mild, moderate and severe overload)
3. As hepatic MRI accurately detects liver iron overload exceeding 50 micromol/g, the upper limit of normal was set at 50 micromol/g for this study
4. Values between 51 and 100 micromol/g will be considered to represent mild iron overload, values between 101 and 200 micromol/g moderate iron overload; and values >201 micromol/g severe iron overload.
5. MRI for quantification of hepatic iron stores will be performed (as possible) at least seven days after iron infusion
Added 18/07/2013:
6. Spleen involvement
7. Heart (cardiac) involvement
Added 23/10/2018:
8. Liver fat fraction measured by R2* relaxometry with IDEAL IQ algorithm and Rennes University Gandon’s algorithm, and iron content in pancreas measured by R2* relaxometry
Secondary outcome measures
1. Analysis of factors determining iron content:
1.1. Demographic characteristics
1.2. Clinical variables
1.3. Dialysis vintage
1.4. Erythropoiesis-stimulating agents (ESA) and iron therapies
1.5. AUDIT score
1.6. Mutation of HFE gene
2. Relationship between hepatic iron content and biochemical makers of iron status and hepcidine-25
Overall trial start date
31/01/2005
Overall trial end date
01/01/2035
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Patients of either sex
2. Undergoing chronic intermittent bipuncture bicarbonate hemodialysis (with ultrapure dialysate single use biocompatible membranes) three times a week
Added 18/07/2013: 3. or peritoneal dialysis
Added 23/10/2018: 4. At initiation of dialysis and with longitudinal follow-up
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
600
Participant exclusion criteria
1. Refusal to participate in the study
2. Poor compliance with the dialysis therapy schedule
3. Age < 18 years
4. Severe cognitive impairment
5. Claustrophobia
6. Hepatic cirrhosis
7. Overt inflammatory or infectious disease
8. Malnutrition
9. Recent major bleeding (< 3 months), major surgery (< 3 months), transfusion dependency, recent transfusion (< 3 months)
10. Intractable malignancy
11. Cardiac pacemakers and metallic cardiac valves
Recruitment start date
01/03/2005
Recruitment end date
31/01/2025
Locations
Countries of recruitment
France
Trial participating centre
Hopital Privé Claude Galien
-
France
Trial participating centre
Hôpital de Melun
-
France
Trial participating centre
Groupe Hospitalier Pitié-Salpétrière
-
France
Trial participating centre
Groupe Hospitalier Kremlin Bicêtre
-
France
Trial participating centre
Centre Nephrocare Marne la Vallée
-
France
Trial participating centre
Polyclinique des Mousseaux
-
France
Trial participating centre
Clinique du Landy
-
France
Trial participating centre
Polyclinique les Fleurs
-
France
Trial participating centre
Hôpital de Mulhouse
-
France
Trial participating centre
Polyclinique du Plateau, Bezons
-
France
Trial participating centre
Clinique Saint-Anne de Strasbourg
-
France
Trial participating centre
CHU de Nancy
-
France
Trial participating centre
Hôpital Privé Jean Mermoz
Lyon
-
France
Sponsor information
Organisation
Quincy Association of Clinical Research and Therapeutics (non profit association, France)
Sponsor details
Association Quincy Recherche Clinique et Therapeutique (QRCT) (France)
4 Rue du Moulin de Jarcy
Quincy Sous Senart
91480
France
-
rostotom@orange.fr
Sponsor type
Research council
Website
Funders
Funder type
Hospital/treatment centre
Funder name
Physicians Association of Claude Galien Hospital (Association Quincy Recherche Clinique et Thérapeutique - QRCT) (France)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
The plan is to publish in 2016:
1. A study on iron stores in peritoneal dialysis patients (last patient included in December 2015)
2. A study on the relationship between liver iron concentration at MRI and HFE mutations C282Y, H63D and S65C
The plan is to publish in 2017 :
1. A replication multicentre study on iron overload in hemodialysis patients (replication of the original monocenter study published in the Am J Med in 2012)
2. A multicentre study for research of heart iron deposits in hemodialysis patients
Added 23/10/2018:
The plan is to publish in 2021:
1. A replication multicentre study on iron overload in hemodialysis patients (replication of the original monocenter study published in the Am J Med in 2012)
2. A monocenter study (Claude Galien, Quincy) for research of pancreatic iron deposits in dialysis patients
3. A multicentre study for research of heart iron deposits in hemodialysis patients
IPD sharing statement
Participant-level data are already available as a supplemental file of the following published article: http://www.ncbi.nlm.nih.gov/pubmed/25506921
These participant-level data are common with the other published article: http://www.ncbi.nlm.nih.gov/pubmed/26182077
The trialists also wish to make the participant-level data available for their next planned publications.
Intention to publish date
Participant level data
Other
Basic results (scientific)
Publication list
2012 results in: https://www.ncbi.nlm.nih.gov/pubmed/22998881
2014 results in: https://www.ncbi.nlm.nih.gov/pubmed/25506921
2015 results in: https://www.ncbi.nlm.nih.gov/pubmed/26182077
2017 results in: https://www.ncbi.nlm.nih.gov/pubmed/28124030
2017 results in: https://www.ncbi.nlm.nih.gov/pubmed/28332280
2017 results in: https://www.ncbi.nlm.nih.gov/pubmed/29270530
2017 results in: https://www.ncbi.nlm.nih.gov/pubmed/29340336
Publication citations
-
Results
Rostoker G, Griuncelli M, Loridon C, Couprie R, Benmaadi A, Bounhiol C, Roy M, Machado G, Janklewicz P, Drahi G, Dahan H, Cohen Y, Hemodialysis-associated hemosiderosis in the era of erythropoiesis-stimulating agents: a MRI study., Am. J. Med., 2012, 125, 10, 991-999.e1, doi: 10.1016/j.amjmed.2012.01.015.
-
Results
Rostoker G, Griuncelli M, Loridon C, Magna T, Machado G, Drahi G, Dahan H, Janklewicz P, Cohen Y, Reassessment of Iron Biomarkers for Prediction of Dialysis Iron Overload: An MRI Study, PLoS One, 2015, 10, 7, e0132006, doi: 10.1371/journal.pone.0132006.
-
Results
Rostoker G, Griuncelli M, Loridon C, Magna T, Janklewicz P, Drahi G, Dahan H, Cohen Y, Maximal standard dose of parenteral iron for hemodialysis patients: an MRI-based decision tree learning analysis, PLoS One, 2014, 9, 12, e115096, doi: 10.1371/journal.pone.0115096.
-
Results
Rostoker G, Griuncelli M, Loridon C, Couprie R, Benmaadi A, Bounhiol C, Roy M, Machado G, Janklewicz P, Drahi G, Dahan H, Cohen Y, Hemodialysis-associated hemosiderosis in the era of erythropoiesis-stimulating agents: a MRI study, Am. J. Med., Am. J. Med., 125, 10, 991-999.e1, doi: 10.1016/j.amjmed.2012.01.015.
-
Results
Rostoker G, Griuncelli M, Loridon C, Magna T, Machado G, Drahi G, Dahan H, Janklewicz P, Cohen Y, Reassessment of Iron Biomarkers for Prediction of Dialysis Iron Overload: An MRI Study, PLoS One, 2015, 10, 7, e0132006, doi: 10.1371/journal.pone.0132006.
-
Results
Rostoker G, Griuncelli M, Loridon C, Magna T, Janklewicz P, Drahi G, Dahan H, Cohen Y, Maximal standard dose of parenteral iron for hemodialysis patients: an MRI-based decision tree learning analysis, PLoS One, 2014, 9, 12, e115096, doi: 10.1371/journal.pone.0115096.
-
Results
Rostoker G, Laroudie M, Blanc R, et al., Signal-intensity-ratio MRI accurately estimates hepatic iron load in hemodialysis patients, Heliyon , 2017, 3, 1, e000226.
-
Results
Rostoker G, Griuncelli M, Cohen Y, HFE gene mutations are not risk factors for iron overload in European hémodialyses patients, Hemodial Int. , 2017 , 21, 3, 440-442, doi: 10.1111/hdi.12552.
-
Results
Issad B, Ghali N, Beaudreuil S, Griuncelli M, Cohen Y, Rostoker G, Hepatic iron load at magnetic resonance imaging is normal in most patients receiving peritoneal dialysis, Kidney Int Rep, 2017 , 2, 6, 1219-1222, doi: 10.1016/j.ekir.2017.07.005.
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Results
Rostoker G, Griuncelli M, Cohen Y, Re: Further evidence supporting the accuracy of quantitative magnetic resonance imaging for evaluating iron load in dialysis patients, Kidney Int Rep, 2017 , 3, 1, 217-218, doi: 10.1016/j.ekir.2017.10.018.