Objective: The primary objective of this proposal is to develop new sensitive and quantitative outcome measures for clinical trials in LBSL. The secondary objective is to identify biomarkers to stratify patients based on disease progression rate.
ID
Source
Brief title
Condition
- Neurological disorders congenital
- Spinal cord and nerve root disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Progression of disease on all parameters.
Secondary outcome
1) to validate the new outcome measures (i.e. is the biomarker predictive) in
this cohort.
2) to establish if pre-symptomatic patients, and severely affected patients
also show progression on the outcome measures under investigation and if that
means these patients will become eligible for clinical studies.
3) acquire normative data on new potential outcome measures in a cohort of
healthy controls.
Background summary
Patients with Leukencephalopathy with Brain Stem involvement and Lactate
elevation (LBSL) develop cerebral white matter abnormalities and a myelopathy
with predominantly degeneration of the pyramidal tracts and dorsal columns.
Although early onset disease (even neonatal) is possible, most patients present
in adulthood with a slowly progressive gait disorder and incontinence.
Currently, there is no disease-modifying treatment and options to quantify
myelopathy are limited. Quantifying disease severity is of the utmost
importance in studies to determine efficacy of new treatments. Recent studies
in other neurodegenerative disorders showed that optical coherence tomography
(OCT) and quantitative MRI (DTI) can distinguish between symptomatic and
asymptomatic patients and worsen with disease progression. These techniques as
well as body sway analysis and gait analysis are potential useful outcome
measures of the severity of the myelopathy in LBSL and other neurodegenerative
diseases with symptoms and signs of myelopathy and will allow for efficient
clinical trial design.
Study objective
Objective: The primary objective of this proposal is to develop new sensitive
and quantitative outcome measures for clinical trials in LBSL. The secondary
objective is to identify biomarkers to stratify patients based on disease
progression rate.
Study design
This study is a 5-year prospective cohort study, with visits to the hospital
every 12 months. For the body sway analysis, gait analysis and MRI studies
matched controls will also be evaluated.
Study burden and risks
Currently, patients with LBSL visit the hospital once a year for a
neurological examination, and MRI scan of the brain (frequency depends on
physician). The frequency of these hospital visits will not change, but
additional data will be collected. There is no treatment intervention and all
study procedures are low-risk.
Healthy controls will only participate in the functional and quantitative
testing (three times in total: at baseline and, 3- and 5-year follow-up) and
MRI scans (two times in total: at baseline and 5-year follow-p), Multiple MRI
scans in healthy controls are necessary for longitudinal comparison with
patients and in order to see whether quantitative MRI measures change over time
in the healthy control group. three times in total: at baseline and , 3-, and
5-year follow-up. Each functional measurement will take about 15 minutes. The
MRI-scan will take about 60 minutes. Participation has no risks.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all
of the following criteria:
- Age > 16 years
- Definite diagnosis of LBSL confirmed by DARS2 mutation analysis.
- Able to understand Dutch or English and provide informed consent.
- No contra-indications for MRI of brain and spinal cord.
Subjects eligible to participate as healthy controls must meet all of the
following criteria:
- Willing to visit the hospital
- 16 years or older
- Provision of written informed consent to participate in the study obtained
from the participant
For the MRI controls
- No contra-indications for MRI of brain and spinal cord.
Exclusion criteria
Pediatric patients
Unable to provide informed conset
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 | NL74024.018.21 |