To investigate whether peripheral nerve ultrasound and DRG MRI can be used as reliable diagnostic and monitoring biomarkers of peripheral nervous system involvement in FA. Specifically, we will examine: 1) Whether conventional peripheral nerve…
ID
Source
Brief title
Condition
- Movement disorders (incl parkinsonism)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Nerve ultrasound:
- Cross-sectional areas of the median, ulnar, tibial, and sural nerve, and
extraforaminal C5, C6, and C7 nerve roots, interscalene brachial plexus
elements, and supraclavicular brachial plexus.
Ultrahigh-frequency nerve ultrasound of the median nerve at the wrist:
- Number of fascicles within the median nerve and their individual
cross-sectional areas.
DRG MRI:
- Volumes of the L3, L4, L5, S1, and S2 DRG.
Secondary outcome
Nerve conduction studies:
- Sensory nerve action potential (SNAP) amplitudes and conduction velocities of
the median, ulnar, and sural nerves.
- Compound muscle action potential (CMAP) amplitudes, motor nerve conduction
velocities, and distal motor latencies of the median, ulnar, and tibial nerves.
Plasma neurofilament light chain concentration.
Clinical measures / questionnaires:
a) Friedreich Ataxia Rating Scale (FARS),
b) Scale for the Assessment and Rating of Ataxia (SARA),
c) Patient-Reported Outcome Measure of Ataxia (PROM-Ataxia),
d) EQ-5D-5L,
e) Patient Health Questionnaire-9 (PHQ-9),
f) Checklist Individual Strength-Fatigue (CIS-Fatigue),
g) Muscle Cramp Scale (MCS) and Cramp Disability Scale (CDS),
h) Neuropathic Pain Scale (NPS),
i) Pittsburgh Sleep Quality Index (PSQI),
j) International Restless Legs Scale (IRLS),
k) Patient Global Impression of Change (PGIC) scale.
Background summary
Although peripheral sensory neuropathy is a major clinical hallmark of
Friedreich ataxia (FA) that contributes significantly to ataxia severity and
disease impact, insights into its underlying mechanisms and data on natural
history are limited. The cross-sectional character of nerve biopsy studies and
post mortem investigations has allowed comparisons of findings between patients
of different ages and different disease severities, but leaves important
knowledge gaps about annual within-subject progression and possible
interindividual differences. Furthermore, there is an urgent need for reliable
imaging markers to monitor disease status and progression in FA. In this study,
we aim to investigate if peripheral nerve ultrasound and dorsal root ganglion
(DRG) MRI can yield reliable diagnostic and monitoring biomarkers of peripheral
nervous system involvement in FA.
Study objective
To investigate whether peripheral nerve ultrasound and DRG MRI can be used as
reliable diagnostic and monitoring biomarkers of peripheral nervous system
involvement in FA. Specifically, we will examine:
1) Whether conventional peripheral nerve ultrasound, ultrahigh-frequency nerve
ultrasound, and DRG MRI are able to adequately differentiate patients with FA
from healthy controls without a neuropathy (i.e., if these techniques could
serve as diagnostic PNS biomarkers).
2) Whether conventional peripheral nerve ultrasound, ultrahigh-frequency nerve
ultrasound, and DRG MRI are able to detect changes at a follow-up measurement
after 1 year (i.e., if they could serve as monitoring PNS biomarkers).
3) Whether ultrasound and MRI abnormalities correlate with relevant
clinician-reported outcome measures, patient-reported outcome measures, and
demographic data.
4) Whether ultrasound-measured cross-sectional areas of lower limb nerves are
associated with volumes of lumbosacral dorsal root ganglia.
5) Whether ultrasound and MRI abnormalities correlate with plasma neurofilament
light chain concentrations, which is a marker of damage to large-caliber
myelinated axons.
Study design
Prospective longitudinal study.
Study burden and risks
The burden for participants consists of two study visits. All measurements are
without significant side effects ("negligible risk").
Geert Grooteplein Zuid 10
Nijmegen 6525GA
NL
Geert Grooteplein Zuid 10
Nijmegen 6525GA
NL
Listed location countries
Age
Inclusion criteria
Friedreich ataxia:
(1) Adults with (2) genetically confirmed FA, and (3) able and willing to sign
the informed consent.
Healthy controls:
Age- and sex-matched healthy controls (without a medical history of
neurological disorders), able and willing to sign the informed consent.
Exclusion criteria
Other diseases or conditions associated with neuropathy (e.g., inflammatory
neuropathy, hereditary neuropathy, previous exposure to cytostatic drugs,
etc.).
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 | NL87256.091.24 |