Objectives Primary objective:- To determine if there is a difference in pro-hepcidin and hepcidin values in blood and urine between Gaucher patients and healthy controls, and between Gaucher patients and hemochromatosis patients. - To gain insight…
ID
Source
Brief title
Condition
- Metabolic and nutritional disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Hepcidin in urine (SELDI-TOF MS)
Pro-hepcidin in blood (ELISA)
Secondary outcome
In blood: sedimentation rate of erythrocytes, C-reactive protein, white blood
count, creatinin, iron, ferritin, hemoglobin, erythrocyes MCV and
total-iron-binding-capacity.
In urine: hepcidin (SELDI-TOF MS) and creatinin.
Background summary
Gaucher disease type I (GD I) is the most common lysosomal storage disorder,
with a prevalence of 1:50.000 in most countries 1. Gaucher disease type I is
characterized by a deficiency of the lysosomal enzyme glucocerebrosidase
(glucosylceramidase), which leads to the accumulation of glucocerebroside in
macrophages. The lipid laden macrophages are called Gaucher cells. The Gaucher
cells are mainly present found in liver, spleen and bone marrow, resulting in
hepatosplenomegaly, skeletal disease and pancytopenia. Ironmetabolism is
altered in Gaucher disease, with high levels of iron and ferritin (zimran 1992,
nierau 1996)
One of the factors involved in iron metabolism and anemia is hepcidin. These 20
and 25 amino acid peptides are produced by the liver and kidney, and were
initially described to be active against bacteria and fungi. Hepcidin is
increased in inflammatory conditions. Their role in iron homeostasis was later
discovered by the finding that mRNA was up-regulated upon iron overload and
decreased by iron depletion in mice. Inappropriately low levels of hepcidin
relative to body iron stores are associated with the abnormal iron homeostasis
characteristic of hemochromatosis. Conversely, over expression of hepcidin
leads to severe iron deficiency and anemia in transgenic mice (ref. Nicolas et
al. 2002).
It is unknown whether hepcidin levels in Gaucher patients are abnormal. In
theory, hepcidin levels could be reduced as an adaptation to the anemia in
Gaucher patients. However, it is also possible that hepcidin levels are
increased due to the chronic low level pro-inflammatory state associated with
Gaucher disease.
In order to gain more insight in iron-homeostais in Gaucher disease, hepcidine
and pro-hepcidine (the inactive pro-peptide of hepcidin) levels in blood and
urine of Gaucher type I patients will be measured and compared to those of
healthy controls and patients with hemochromatosis.
Study objective
Objectives
Primary objective:
- To determine if there is a difference in pro-hepcidin and hepcidin values in
blood and urine between Gaucher patients and healthy controls, and between
Gaucher patients and hemochromatosis patients.
- To gain insight in fluctuations/changes in hepcidin values in time in healthy
controls and in Gaucher patients receiving therapy.
Secondary objective:
- To see if the simple detection of pro-hepcidin values in blood can be used as
a method to monitor circulating hepcidin levels. This will be achieved by
determining the correlation of pro-hepcidin values in blood samples with
hepcidin levels in urine monsters.
Study design
An observational pilot study will be performed in which hepcidine and
pro-hepcidine will be measured in blood and urine from 20 hemochromatosis
patients, 20 Gaucher patients and 20 healthy controls. If possible, blood and
urine samples from Gaucher patients and healthy controls will be taken from
stored samples. Additional samples from Gaucher patients and healthy controls
will be sampled according to this study protocol. Healthy controls will be
asked personally by the invesigator to participate in this study. The blood and
urine samples of hemochromatosis patients will be taken during their regular
visit for therapeutic phlebotomy.
Study burden and risks
From hemochromatosis patients a total of 35 ml blood will be obtained. Since
blood will also be drawn for therapeutic phlebotolomy, no extra vena puncture
will be performed, nor will extra blood be drawn. From healthy controls 42 ml
blood will be obtained for which a vena puncture will be performed.
From hemochromatosis patients, Gaucher patients and healthy controls one
specimen of mid-stream urine will be asked during a routine visit to the
hospital.
Meibergdreef 15
1105 AZ
Nederland
Meibergdreef 15
1105 AZ
Nederland
Listed location countries
Age
Inclusion criteria
-Patients, older than 18 years, with proven GD I, as evidenced by decreased plasma glucocerebrosidase activity or genotyping.
-Controls, older than 18 years with a normal total iron binding capacity in blood.
-Patients with proven Hematochromatosis as evidenced by total iron bindingcapacity of > 45% in blood or genotyping.
-Patients and controls have to provide written informed consent to participate in the study.
Exclusion criteria
none
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
CCMO | NL13723.018.06 |