The goals of this study are to examine the aetiology and daily impact of peripheral neuropathy in MLD patients over time, and to identify dynamic biomarkers that correlate with the severity of peripheral neuropathy over time, and might predict…
ID
Source
Brief title
Condition
- Neurological disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary study parameters will be the:
Total pmTNS score (between 0 * 32) and nerve conduction velocities (m/s) of the
radial nerve, ulnar nerve, tibial nerve and common peroneal nerve in MLD
patients at three different time points, and the changes in the total pmTNS
score and NCV over time.
Correlation between levels of different sulfatide species and biomarkers
(protein level) in CSF and blood and the severity of peripheral neuropathy in
MLD patients at three different time points and over time.
Changes in size, vascularity and echogenicity of the radial nerve, ulnar nerve,
tibial nerve and common peroneal nerve in MLD patients over time.
Secondary outcome
The secondary study parameters will be the:
Calculated differences in total pmTNS scores and nerve conduction velocities at
baseline between different MLD patient subgroups.
Absolute levels of sulfatide and elevated or lowered biomarkers in CSF and
blood in MLD patients at three different time points and the calculated
differences with these levels in CSF and blood in healthy controls.
Correlation between size, vascularity and echogenicity of the radial nerve,
ulnar nerve, tibial nerve and common peroneal nerve and different stages of the
disease.
Background summary
Metachromatic leukodystrophy (MLD) is a lethal metabolic disease characterized
by deficient enzyme activity of arylsulfatase A (ASA) and accumulation of
sulfatides in the nervous system. A part of the Dutch MLD patients is currently
treated with hematopoietic stem cell transplantation (HCT), but this treatment
mainly impacts the brain white matter whereas the peripheral neuropathy shows
no or limited response to HCT. In our experience, peripheral neuropathy
contributes significantly to morbidity in MLD patients but scientific data
about the etiology, severity, and predictive biomarkers in these patients are
lacking.
Study objective
The goals of this study are to examine the aetiology and daily impact of
peripheral neuropathy in MLD patients over time, and to identify dynamic
biomarkers that correlate with the severity of peripheral neuropathy over time,
and might predict peripheral neuropathy progression after treatment.
Study design
It is a multi center study that uses a longitudinal cohort study design. The
cohort consists of 40 pediatric and adult MLD patients (aged 4 * 50 years).
Data collection will take place during a period of three years. Each year, the
research participants will undergo the same procedures: examination according
to the Pediatric-modified Total Neuropathy Score (pmTNS), ultrasound and
electromyography (EMG) of the peripheral nerves, and cerebrospinal fluid (CSF)
and venous blood sampling. In this manner we can observe changes in levels of
(lyso)sulfatide and different biomarkers in CSF and blood, and in
electrophysiological and morphological characteristics of the peripheral nerves
over time. We will use historical data providing information on these
characteristics of (age-matched) healthy controls for comparison.
Study burden and risks
The procedure includes one hospital visit per year for three years, combined
with the standard follow-up appointments. There is no direct benefit for the
participants; there is only benefit for the patient population by increased
knowledge. Risks and burdens of the study will be minimized by collecting
samples and data from standard care procedures as much as possible.
De Boelelaan 1118
Amsterdam 1081 HV
NL
De Boelelaan 1118
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
Diagnosis of MLD confirmed by demonstrating a deficiency of ASA activity in
leukocytes, increased urinary sulfatide levels and/or pathogenic ARSA
mutations.
Exclusion criteria
No informed consent (IC) given by the participant or given by parents/legal
representative if necessary
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 | NL69005.029.19 |