The main objective of this project is to identify the early brain changes in MS (i.e. patients that are recently diagnosed with MS) that can be measured by advanced structural and functional (network) imaging measures. Additionally, we will…
ID
Source
Brief title
Condition
- Demyelinating disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Changes in structural MRI (i.e. atrophy and (grey matter) lesions) will serve
as primary outcome measures, such as atrophy in the cortex and deep grey
matter, changes in white matter damage in specific tracts and white matter and
cortical lesions.
Next, changes in functional brain measures will be included, measuring for
instance functional connectivity, eigenvector centrality mapping and functional
brain adaptation.
Secondary outcome
Changes in cognitive performance (as measured with the neuropsychological
examination) and clinical performance (as measured with the neurological
examination) will serve as secundary parameters. Additionally, changes on
questionnaires (e.g. arm and walk function, fatigue, anxiety and depression,
subjective cognitive perfor-mance, coping style, mastery, stress, work
participation and quality of life) will be included.
Molecular brain changes will also be investigated, addressing for example
changes in GABA/glutamate and serum biomarkers NfL and GFAP.
Background summary
Within five years after diagnosis, approximately 50% of the patients with
multiple sclerosis (MS) develop cognitive decline and 65% of the patients
become unemployed, negatively impacting the quality of life. To be able to
postpone or ultimately prevent these negative effects of MS, we urgently need
to understand which underlying mechanism(s) lead to such a rapid decline in
daily functioning and whether we can predict such an early clinical and
cognitive decline. It is expected that especially in this early phase of the
disease a window of opportunity for neuroplasticity exists (functional
reorganization, brain and cognitive reserve), which is not yet exhausted due to
a relatively limited amount of brain tissue damage. Understanding these early
changes is key to develop new treatment targets in order to halt the disease,
i.e. to identify a window-of-opportunity for early intervention. Until now,
these very early changes, measured with advanced imaging and biomarkers, remain
unknown.
Study objective
The main objective of this project is to identify the early brain changes in MS
(i.e. patients that are recently diagnosed with MS) that can be measured by
advanced structural and functional (network) imaging measures. Additionally, we
will determine how and when these changes relate to clinical and cognitive
decline and serum biomarkers. Finally, we will determine which of the measures
is most predictive for clinical and cognitive decline in patients recently
diagnosed with relapsing-remitting MS (RRMS). Ultimately we would like to
introduce (a) new biomarker(s) (or combinations of biomarkers) to detect the
first pathological changes in patients with MS. The detected outcome measures
can serve as novel outcomes in clinical trials and may open a new road towards
precision medicine.
Study design
This 2-year prospective, longitudinal, single center, observational cohort
study will be performed at the Amsterdam UMC, in which recently diagnosed MS
patients will be followed over time with regard to cognitive and clinical
performance, and structural and functional (imaging) measures.
Study burden and risks
All subjects in this study will visit the Amsterdam UMC, location AMC three
times: at baseline, after 1 year and after 2 years. For the patients the visits
will consist of a neurological examination, a neuropsychological examination,
blood sampling (6 mL) and MR imaging (structural and functional). At home,
patients will fill out several questionnaires on arm and walkfunction, fatigue,
anxiety and depression, subjective cognitive performance, coping style,
mastery, stress, work participation and quality of life. Additional blood
samples (6 mL) will be drawn at month 3, month 6, month 9, month 15, month 18
and month 21.
Healthy control subjects will undergo a similar protocol, except for the
neuropsychological examination.
The burden will be mainly the time-investment in the study. Risks are limited
due to the observational character of the study. However, it is possible that
coincidental findings will be shown via the MRI-scans. In case of coincidental
findings by participants the researcher will ask the radiologist to review the
scans. In case of coincidental findings in patients, their neurologist will be
informed. In case of coincidental findings in healthy controls, their general
practitioner will be informed.
De boelelaan 1108
Amsterdam 1081 HZ
NL
De boelelaan 1108
Amsterdam 1081 HZ
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet the
following eligibility criteria at baseline:
1. Ability to understand the purpose and risks of the study and provide signed
and dated informed consent and authorization to use protected health
information (PHI) in accordance with national and local subject privacy
regulations;
2. All participants should be 18-65 years of age;
3. Sufficient Dutch proficiency to be able to comprehend and to perform the
neuropsychological examination;
4. All participants need to meet the safety criteria to undergo an MRI
examination;
For the patients specifically:
5. Only patients that are recently (between 6 up to 12 months) diagnosed with
clinically definite MS according to the 2017 revision of the McDonald MS
criteria will be included (a range of one month before and after this window
was applied; thus 5-13 months);
6. Only patients with (active) relapsing-remitting disease course will be
included;
7. All types of disease modifying treatment for MS are allowed.
Exclusion criteria
Subjects will be excluded from study entry if any of the following exclusion
criteria exist at baseline:
1. Unable or unwilling to provide informed consent;
2. Presence or history of alcohol or drug abuse;
3. Presence or history of psychiatric or neurological disease of the CNS (for
patients: neurological disease other than MS) that is expected to affect any of
the outcome measures (will be discussed with the principal investigator and
neurologist);
4. Presence of contra-indications for MRI;
5. Participation in other (scientific) studies using cognitive or physical
training programs (interventions other than standard care) at baseline to avoid
noise.
For the patient groups specifically:
6. Patients with disease categorized as clinically isolated syndrome, primary
progressive, secondary progressive or progressive relapsing;
7. Relapses or steroid treatment less than four weeks prior to the visits.
Visits of included patients experiencing a relapse will be postponed if
possible;
8. Patients undergoing a cognitive relapse. Visits of included patients
experiencing a cognitive relapse will be postponed if possible.
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 | NL72064.029.20 |