A cohort study of haemodialysis patients based on hepatic magnetic resonance imaging
| ISRCTN | ISRCTN80100088 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN80100088 |
- Submission date
- 20/05/2011
- Registration date
- 14/06/2011
- Last edited
- 13/09/2022
- Recruitment status
- Stopped
- Overall study status
- Stopped
- Condition category
- Urological and Genital Diseases
Plain English summary of protocol
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
Contact information
Scientific
Service de Néphrologie et de Dialyse
Hopital Privé Claude Galien
20 route de Boussy
Quincy Sous Senart
91480
France
 ORCID ID |
0000-0002-4383-3825 |
|---|---|
| rostotom@orange.fr |
Scientific
Service de Néphrologie et de Dialyse
Hôpital Privé Claude Galien
20 route de Boussy
Quincy-sous-Sénart
91480
France
| rostotom@orange.fr |
Scientific
Service de Néphrologie et de Dialyse
Hôpital Privé Claude Galien
20 route de Boussy
Quincy-sous-Sénart
91480
France
| rostotom@orange.fr |
Study information
| Study design | Prospective cross-sectional longitudinal multicenter study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cross-sectional longitudinal study |
| Study setting(s) | Hospital |
| Study type | Diagnostic |
| Participant information sheet | Not available in web format, please contact rostotom@orange.fr to request a patient information sheet |
| Scientific title | Analysis of hepatic iron stores of haemodialysis patients by magnetic resonance imaging: a cross-sectional and longitudinal study |
| Study objectives | 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(s) | 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 |
| Health condition(s) or problem(s) studied | 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 |
| 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 study start date | 31/01/2005 |
| Completion date | 01/01/2035 |
| Reason abandoned (if study stopped) | This study was stopped at the end of February 2020 due to the COVID-19 pandemic. |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 600 |
| Total final enrolment | 411 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 01/03/2005 |
| Date of final enrolment | 31/01/2025 |
Locations
Countries of recruitment
- France
Study participating centres
France
France
France
France
France
France
France
France
France
France
France
France
-
France
Sponsor information
Research council
Association Quincy Recherche Clinique et Therapeutique (QRCT) (France)
4 Rue du Moulin de Jarcy
Quincy Sous Senart
91480
France
| rostotom@orange.fr |
Funders
Funder type
Hospital/treatment centre
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Other |
| 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 plan | 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. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/10/2012 | Yes | No | |
| Results article | results | 15/12/2014 | Yes | No | |
| Results article | results | 16/07/2015 | Yes | No | |
| Results article | results | 05/01/2017 | Yes | No | |
| Results article | results | 01/07/2017 | Yes | No | |
| Results article | results | 23/07/2017 | Yes | No | |
| Results article | results | 21/11/2017 | Yes | No | |
| Results article | results | 01/01/2019 | Yes | No | |
| Results article | Calcific uremic arteriolopathy analysis in the total final 358 dialysis patients | 23/01/2021 | 13/09/2022 | Yes | No |
| Results article | Results | 05/07/2022 | 13/09/2022 | Yes | No |
Editorial Notes
13/09/2022: The following changes have been made:
1. Publication references added.
2. The total final enrolment has been added.
3. The overall trial status has been changed to stopped.
05/05/2020: Due to current public health guidance, recruitment for this study has been paused.
11/02/2019: Internal review.
11/12/2018: Publication reference added.
01/11/2018: Internal review.
23/10/2018: The following changes were made to the trial record:
1. The contacts, interventions, primary outcome measures, inclusion criteria, publication and dissemination plan were updated.
2. Hôpital de Valenciennes was removed and Polyclinique du Plateau, Bezons was added as trial participating centres.
3. The recruitment end date was changed from 31/01/2020 to 31/01/2025.
4. Publication references added.
5. The overall trial end date was changed from 31/01/2020 to 01/01/2035.
26/06/2017: Hôpital Privé Jean Mermoz was added as a trial participating centre.
25/01/2016: Hôpital de Valenciennes, Clinique Saint-Anne de Strasbourg and CHU de Nancy (France) were added as trial participating centres.
04/11/2015: The following changes were made to the trial record:
1. The overall trial end date was changed from 31/01/2015 to 31/01/2020.
2. The target number of participants was changed from 400 to 600.
18/07/2013: The following changes were made to the trial record:
1. The study design was changed from "Prospective cross-sectional longitudinal study" to "Prospective cross-sectional longitudinal multicenter study".
2. The overall trial end date was updated from 31/01/2014 to 31/01/2015.
3. The target number of participants was updated from 300 to 400.
30/11/2012: The following changes were made to the trial record:
1. The overall trial end date was updated from 31/01/2012 to 31/01/2014.
2. The target number of participants was updated from 200 to 300.
