To determine whether damage in the cortical and/or subcortical GM in patients with early RRMS increases in regions connected to more damaged WM tracts, i.e. WM tracts with larger lesion volume, WM tracts with more severe damage inside lesions, and/…
ID
Source
Brief title
Condition
- Demyelinating disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Three measures for WM damage will be assessed, i.e. lesion volume, lesion
fractional anisotropy (FA) and NAWM FA, from which a composite WM damage score
will be computed. High versus low WM damage scores will then be compared to the
atrophy rates in the GM, based on subcortical volume and cortical thickness
measures. From this, we can compare atrophy rates of each GM structure from
baseline to follow-up 1 between the group of patients with higher damage in the
WM tracts connected to that GM structure on the one hand, and the group of
patients with lower damage in those WM tracts on the other.
Similar calculations will be performed between follow-up 1 and follow-up 2 in
order to determine whether a larger increase of WM damage over the first study
year is predictive of faster subsequent GM atrophy in the second year.
Secondary outcome
Next to the measures for GM and WM damage, resting state functional
connectivity measurements will be used to assess whether GM and WM damage
patterns effect the functional organization of the brain at rest, either prior
to GM/WM damage, or following the damage patterns observed.
Furthermore, clinical measurements will be taken into account, in order to link
the structural data to functionality of the brain in the RRMS patients.
Background summary
It is currently unclear whether and how atrophy of the brain*s grey matter (GM)
in multiple sclerosis (MS) is related to pathological changes in white matter
(WM). This knowledge is needed to determine whether treatment efforts aimed at
the neurodegenerative component of MS are targeting a primary disease
mechanism, or in fact merely treating secondary symptoms. Atrophy of the
connected (sub)cortical GM, i.e., the change of volumes of deep GM structures
and change of cortical thickness of cortical GM regions, can thus be related to
location and severity of WM damage. We will analyze local rates of atrophy in
distinct cortical and subcortical GM regions in early relapsing-remitting MS
(RRMS) patients at three time points (baseline, follow-up 1 [baseline + 1 jaar
± 3 months] and follow-up 2 [follow-up 1 + 1 jaar ± 3 months]) to determine
whether the rate of GM atrophy of a specific region is related to the amount of
pre-existing WM damage and/or its early rate of change. In this way, this
project will deliver valuable quantitative longitudinal data on RRMS patients
to understand the relations between WM pathology and subsequent GM atrophy in
early RRMS patients.
Study objective
To determine whether damage in the cortical and/or subcortical GM in patients
with early RRMS increases in regions connected to more damaged WM tracts, i.e.
WM tracts with larger lesion volume, WM tracts with more severe damage inside
lesions, and/or more severe NAWM damage, and to see whether a larger increase
of damage over the first study year is predictive of faster subsequent GM
atrophy in the second year.
Second, to determine how the structural changes in early RRMS patients effect
the functionality of the brain, as measured by i.e. functional connectivity and
several clinical parameters.
Study design
The study proposed here is a follow-up study in which GM atrophy rates and
changes of WM tract damage are quantified over two consecutive ±1-year
intervals. For this, 40 MS patients and 15 healthy controls will be included,
taking the inclusion criteria in consideration. At baseline, follow-up 1 and
follow-up 2, MRI measurements will be performed to study brain volume,
functional connectivity, lesion load, tract damage and WM integrity.
Furthermore, clinical parameters are measured as well to relate the MRI
measurements to functionality.
At each time point, measurements of GM atrophy, WM damage and functionality
(i.e. fMRI and clinical parameters) will be performed. Per time point, GM
atrophy is related to WM tract damage to identify WM tracts connected to each
GM region and to quantify damage therein, which will be related to functional
parameters. Over two consecutive ±1-year intervals, the measured GM atrophy
rates will be compared between patient groups with high WM damage and low WM
damage in order to determine whether the rate of GM atrophy is predictive of
later WM tract damage, and/or vice versa.
Study burden and risks
No risks are associated with MRI acquisition and no direct benefits are
expected for the patients
De Boelelaan 1118
Amsterdam 1081HZ
NL
De Boelelaan 1118
Amsterdam 1081HZ
NL
Listed location countries
Age
Inclusion criteria
Patient group:
1. Minimum age 18 years
2. Clinical definite relapsing remitting MS for < 5 years
3. Either receiving no treatment , or receiving first line treatment for at least 6 months
4. Expanded Disability Status Score (EDSS) * 5.0
5. Written informed consent ;Control group:
1. Minimum age 18 years
2. Written informed consent
Exclusion criteria
1. Past or current clinical relevant non-MS neurological or psychiatric disorder(s)
2. Past or current clinical relevant (auto)immune disorder(s)
3. Treatment with first line therapy for less than 6 months
4. Treatment with second line therapy
5. Relapse and/or steroid treatment in past 3 months
6. Pregnancy
7. MRI incompatibility, e.g. metal objects in or around the body, claustrophobia or inability to lie still in the scanner
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 | NL57713.029.16 |