|- candidate number||28549|
|- NTR Number||NTR7023|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||7-feb-2018|
|- Secondary IDs||N161876.015.17 CCMO|
|- Public Title||SATURNUS Study|
|- Scientific Title||The transferrin saturation/hepcidin ratio: a study on the diagnostic value in the differentiation of iron refractory iron deficiency anemia from iron deficiency anemia|
|- ACRONYM||SATURNUS Study|
|- hypothesis||The TSAT/hepcidin ratio can be used as a diagnostic tool to differentiate between IRIDA and other disorders presenting with iron deficiency anemia with a high specificity.|
TSAT = transferrin saturation
IRIDA = Iron Refractory Iron Deficiency Anemia
|- Healt Condition(s) or Problem(s) studied||Iron deficiency anemia (IDA), Iron refractory iron deficiency anemia (IRIDA), Hepcidin, Transferrin saturation|
|- Inclusion criteria||IRIDA group|
In order to be included in the IRIDA group a patient should meet the criteria for IRIDA:
o Previous diagnosis as a mono-allelicorbi-allelicI RIDA patient with an IRIDA phenotype detected after clinical presentation
o Presence of microcytic anemia (MCV < 80 fL, Hb <7.5 mmol/L for women, Hb < 8.5 mmol/L for men)
o Absence of inflammation(CRP<10mg/L)
o Not or partially responsive to oral iron
Responsiveness to oral iron defined as Hb increment of 2 g/dL after 3 weeks of iron therapy
o Age above 18 years
o Determined and available TSAT/hepcidin ratio, determined in the absence
Based on these criteria 4 patients in a population of 21 will be excluded because either the patient was <18 years or the TSAT/hepcidin ratio was not available, or not available in the absence of inflammation.
The other 17 IRIDA patients will be included in the study; 11 IRIDA patients in the bi-allelic affected group, with a homozygous or a compound heterozygous TMPRSS6 defect, and 6 subjects in the mono-allelic affected group with a heterozygous TMPRSS6 defect.
(Donker et al, Am J Hematol 2016, see below)
Because the controls in the SATURNUS study all have a microcytic anemia comparable with the IRIDA group, the phenotype is not discriminative. Therefore, in all controls genotyping of the exons of TMPRSS6 will be performed. A relevant phenotype, see below, in combination with the absence of pathological TMPRSS6 variants on both alleles will be defined as non-IRIDA and will be eligible as control.
Inclusion of subjects in the control group will take place at the gynaecological and gastrointestinal department of the Máxima Medical Centrum Veldhoven. In order to be eligible to participate in this study a subject should meet the following prescreening criteria:
o Presence of microcytic anemia (MCV <80 fL and Hb <7.5 mmol/L L for women, Hb < 8.5 mmol/L for men)
After confirmation of the prescreening criteria a subject should meet the following inclusion criteria to be included in the study:
o Presence of microcytic anemia (MCV < 80 fL and Hb <7.5 mmol/L for women, Hb < 8.5 mmol/L for men)
o Low TSAT (TSAT <10%)
o Absence of inflammation(CRP<10mg/L)
o Absence of pathological TMPRSS6 variants in exons of both alleles
|- Exclusion criteria||Control group|
Subjects with the following criteria will not be able to participate in the study because these criteria interfere with the TSAT and hepcidin values.
o Oral iron supplements in the last 3 months before referral to the gynaecologist or gastrointestinal specialist
o Diagnosis with any disease associated with inflammation including malignancies, chronic liver and kidney diseases
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||2 or more arms, non-randomized|
|- planned startdate ||1-mrt-2018|
|- planned closingdate||1-mrt-2019|
|- Target number of participants||94|
|- Primary outcome||Cut off point TSAT/hepcidin ratio for discrimination between IRIDA en IDA not because of IRIDA|
The main study outcome is a cut off point for the TSAT/hepcidin ratio that discriminates IRIDA
from iron deficient anemia (IDA) because of other reasons than IRIDA with a high specificity.
|- Secondary outcome||TSAT/hepcidin ratio in IDA, to be compared with TSAT/hepcidin ratio in healthy individuals
The study will generate data on the mean and interquartile ranges of the TSAT/hepcidin ratio of the IRIDA patients (n=17) and the mean and interquartile ranges of the TSAT/hepcidin ratio
of the control group diagnosed with IDA because of other reasons than IRIDA.
The data on the TSAT/hepcidin ratios in controls with IDA because of other reasons than IRIDA will be compared with data on TSAT/hepcidin ratios in healthy individuals that have been established earlier in order to determine if there is any difference between these groups.
Number of pathological TMPRSS6 variants in IDA patients referred to gastro-enterologist and
Pathological TMPRSS6 variants may be found in the control patients that have been referred to gastro-enterologist or gynaecologist for analysis of IDA. In these control patients IDA has been incorrectly exclusively attributed to gastrointestinal or gynaecological blood loss and/or malabsorption since IRIDA has not been considered earlier.
|- Timepoints||Single blood withdrawal at out patient department for determination of Hb, indices, iron parameters, serum hepcidin and TMPRSS genotyping|
|- Trial web site||not applicable|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES|| Albertine Donker|
|- CONTACT for SCIENTIFIC QUERIES|| Albertine Donker|
|- Sponsor/Initiator ||Maxima Medical Center, Veldhoven|
(Source(s) of Monetary or Material Support)
|Radboud University Medical Center Nijmegen, Maxima Medical Center, Veldhoven|
|- Publications||SATURNUS studie is vervolg op:|
Donker et al. Iron refractory iron deficiency anemia: a heterogeneous disease that is not always iron refractory. Am J Hematol. 2016 Dec;91(12):E482-E490. doi: 10.1002/ajh.24561.
|- Brief summary||In this observational study a total of 17 IRIDA patients from a population earlier studied by Donker et al. will be included. TSAT/hepcidin ratios have already been determined in these patients.|
Control subjects will be asked to participate in the study by their treating physician (gynecologist, gastrointestinal specialist, Maxima Medical Center, Veldhoven, The Netherlands) if a microcytic anemia with a ferritin below the reference value has been determined. They will receive the study information and informed consent form. If subjects are eligible for inclusion in this study and are willing to participate informed consent will be signed at the next appointment in the hospital.
After the subjects have signed the informed consent, study blood samples will be collected for determination of Hb, MCV, MCH, CRP, iron parameters, hepcidin and DNA sequencing of the exons ofTMPRSS6.
|- Main changes (audit trail)|
|- RECORD||7-feb-2018 - 3-mrt-2018|