To assess the ability of MRI techniques to detect early stages of lipid accumulation in the liver of ASMD patients with the chronic visceral subtype compared to values of age-, sex- and BMI-matched healthy subjects.
ID
Source
Brief title
Condition
- Inborn errors of metabolism
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Fat fraction in volume percentage (%) measured with MRS of ASMD patients
compared to values of healthy subjects.
Secondary outcome
- to assess whether MRS is able to specifically distinguish SM accumulation
from lipid accumulation in liver tissue.
- to assess the effect of therapy on the fat fraction and liver stiffness in
the patients that are eligible to start treatment.
- to identify patients with liver involvement of ASMD by assessing the
correlation between the fat fraction and liver stiffness and markers of liver
involvement of ASMD.
- to assess the correlation of the fat fraction and liver stiffness with other
biomarkers for ASMD.
Background summary
Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disorder
caused by a deficiency of sphingomyelinase resulting in accumulation of the
sphingolipid sphingomyelin in the liver, spleen and lungs. Enzyme replacement
therapy (ERT, olipudase alfa, Sanofi Genzyme) is currently investigated in a
phase 2/3 trial and is expected to get market approval in the second half of
2022. Accumulation of sphingomyelin in the liver leads to liver fibrosis in a
subset of ASMD patients. As ASMD is a slowly progressive disease, detection of
early stages of sphingomyelin storage in the liver might aid in identifying
patients at risk for major manifestations who would benefit from therapy. Two
magnetic resonance (MR) based techniques might be of interest: MR Spectroscopy
(MRS) to measure lipid accumulation (steatosis) and MR Elastography (MRE) to
measure liver stiffness (fibrosis).
Study objective
To assess the ability of MRI techniques to detect early stages of lipid
accumulation in the liver of ASMD patients with the chronic visceral subtype
compared to values of age-, sex- and BMI-matched healthy subjects.
Study design
Cross-sectional pilot study in which MRS and MRE measurements of ASMD patients
will be compared to values of age-, sex- and BMI-matched healthy subjects. All
ASMD patients who participate will undergo an MRI during their yearly
assessments. Patients eligible for therapy will also undergo an MRI after one
year of treatment. Healthy subjects will undergo one MRI.
Study burden and risks
The MRI procedure yields no risk: at most patients might feel uncomfortable
lying in tight space. Patients will not directly benefit from participation in
the study. The results of the study may improve clinical care in the future.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
Patients:
- The patient has biochemically proven ASMD (preferably genetically confirmed)
- The patient is >= 18 years of age
- The patient is willing and able to provide written informed consent prior to
the study-related procedure.
Healthy controls:
- The individual is willing and able to provide written informed consent prior
to the study-related procedure
- The individual is >= 18 years of age
- General good health as determined by medical history
Exclusion criteria
ASMD patientes and healthy controls:
- Inability to adhere to the study protocol
- Inability to undergo an MRI procedure
Design
Recruitment
Medical products/devices used
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 | NL80644.018.23 |