To determine whether different MR-based imaging techniques and FibroScan can be used for the purpose of identifying and monitoring Gaucher Disease patients at high risk of developing disease related liver complications.
ID
Source
Brief title
Condition
- Endocrine disorders congenital
- Hepatic and hepatobiliary disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The differences between Gaucher Disease patients with high risk versus normal
risk and Gaucher Disease patients versus healthy volunteers in:
-Elasticity measurements of the liver obtained with MR Elastography and
FibroScan
-Iron accumulation in the liver assessed by MRI and biochemical values.
Secondary outcome
The differences between Gaucher Disease patients with high risk versus normal
risk and Gaucher Disease patients versus healthy volunteers in: The spectrum of
glucosylceramide in the liver obtained with 1H-MR Spectroscopy.
Background summary
Gaucher disease is a hereditary lysosomal storage disorder. The deficiency in
glucocerebrosidase leads to accumulation of glucocerebroside or "gaucheromas"
within the body. Gaucher disease patients typically show high serum ferritin
levels as well. One of the long term complications of the disease within the
liver are increased risk of fibrosis, cirrhosis and hepatocellular carcinoma
(HCC). The pathophysiology behind this phenomenon is still largely unknown. We
hypothesize that iron accumulation and/ or glucocerebroside storage cause
fibrotic and cirrhotic changes to occur and that this mechanism is responsible
for the increased risk of HCC as seen in Gaucher disease. However, this has
never been investigated due to a lack of safe and reliable diagnostic tools.
Newly available imaging techniques could be of value in the early detection and
subsequent monitoring of these complications. MR Elastography as well as
FibroScan can detect liver fibrosis by measuring liver elasticity. Also, an
algorithm was designed to asses liver iron content from MRI measurements.
Proton-MR Spectroscopy (1H-MRS) is another MRI based method which can quantify
different metabolites within tissues. 1H -MRS is most commonly used for the
quantification of fat within the liver. It is unknown whether 1H -MRS can
measure the amount of glucocerebroside within liver tissue. It would therefore
be valuable to test our hypotheses by investigating the value of these
non-invasive imaging techniques in patients with Gaucher disease.
Study objective
To determine whether different MR-based imaging techniques and FibroScan can be
used for the purpose of identifying and monitoring Gaucher Disease patients at
high risk of developing disease related liver complications.
Study design
This is a single-centre observational pilot study. Both patients and healthy
volunteers will be included. The study is not randomized and patients will be
non-consecutively included. Patients with from the Endocrinology outpatient
clinic who meet the inclusion criteria will be informed about the study. After
giving informed consent they will be included in the study.
Healthy volunteers will be recruted by means of sending out flyers thoughout
the AMC. Healthy volunteers will be age and sex matched with the mild Gaucher
patient group. After giving informed consent they will be included in the
study.
Study burden and risks
There are no significant risks associated with the interventions. The
procedures will require:
-10-20 minutes in the 1.5 Tesla MRI scanner
-30-40 minutes in the 3 Tesla MRI scanner
-15 minutes for FibroScan at the Gastroenterology Department
-Drawing of 2-3 extra tubes of blood voor Gaucher Disease patients added to
regular blood drawing.
Due to logistics, patients might have some waiting time in between the
different procedures. We will try to plan all three interventions on the same
day, and keep waiting time as short as possible.
Participants will fill out a checklist to identify any possible
contra-indications for MRI scanning. Participants with contra-indications for
MRI will excluded from this study. During MRI scanning, the patient will have
to lie still on his or her back in a MRI scanner. Both MRI and FibroScan are
non-invasive, non-ionizing examinations. No contrast medium will be
administered. Patients with Gaucher Disease routinely visit the outpatient
clinic in the AMC four times a year. Whenever possible, we will try to combine
the two MRIs and FibroScan with visiting the outpatient clinic. However, due to
scanning capacity this might not always be achievable. Therefore, participating
in this pilot study might require an extra visit to the AMC. The best available
option will be considered for each participant separately.
Participating in this study has no direct advantage for the patient, except
extra insight in their disease. Patients are not delayed in treatment for their
disease. Apart from the possible extra visit to the hospital and lying in the
MRI scanner, there will be little extra physical and psychological discomfort
associated with participation.
Meibergdreef 9
1105 AZ Amsterdam
NL
Meibergdreef 9
1105 AZ Amsterdam
NL
Listed location countries
Age
Inclusion criteria
Patients with Gaucher Disease;
Over 18 years of age;
BMI under 27 kg/m2;
At least 2 years of therapy;
Written informed consent
Exclusion criteria
Known history of chronic liver disease other than caused by Gaucher Disease;
Alcohol more than 3 units per day for males and more than 2 units per day for females;
Contra-indications for MRI scanning (standard checklist);
younger than 18 years of age;
use of medications that are known to affect the liver (see protocol)
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 | NL30863.018.09 |