Primairy objective:* To assess whether a poor vitamin D status in RRMS patients is negatively associated with cognitive performance in neuropsychological tests (information processing speed and working memory) and with measures of cognitive (dys)…
ID
Source
Brief title
Condition
- Autoimmune disorders
- Demyelinating disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Psychometric assessments prior to MRI assessment:
* Paced Auditory Serial Addition Test (PASAT)
* Symbol Digit Modalities Test (SDMT)
Functional MRI assessments:
* Task related fMRI, using the Sternberg paradigm (working memory function)
* Resting State fMRI, functional network integrity
* DTI, structural network integrity
* MR Spectroscopy, assessment of neurotransmitters GABA and glutamate
Serum sampling for assessment of:
* Vitamin D status (25(OH)D serum level)
* Vitamin B12 status (Cobalamin serum level)
- Cytokines in serum
Secondary outcome
Psychometric assessments:
-Fatigue will be measured with the Fatigue Severity Scale (FSS)
-Depression will be measured with the depression-subscale of the hospital
anxiety and depression scale (HADS)
-Premorbid intelligence will be measured with the Nederlandse Leestest voor
Volwassenen (NLV)
Conventional MRI assessments:
-T1-weighted images, for volumetric assessment (atrophy)
-T2-weigthed FLAIR acquisition for lesion load assessment
-Double Inversion Recovery (DIR), cortical lesion assessment
Background summary
Vitamin D is traditionally considered as exclusively important for calcium
homeostasis. Recent years, other biological functions of vitamin D gained
attention. In multiple sclerosis (MS), a poor vitamin D status has been
associated with an increased hazard on relapses, and with an increased amount
of MS disability. However, other symptoms of MS have also been associated with
vitamin D status. We found that a poor vitamin D status correlated negatively
with the presence of depressive symptoms in MS. Recently, a prospective
longitudinal cohort study in healthy elderly showed an association between a
poor vitamin D status, and an increased hazard on cognitive decline. Cognitive
impairment is also a frequent and disabling symptom, which is even found in
early MS. Additionally, functional MRI analysis revealed subtle changes in
connectivity and functional organization, indicating compensatory
reorganization. This was especially observed in patients lacking severe
cognitive complaints. In this project, we will explore the link between vitamin
D status and signs of cognitive impairment in MS.
This research is important, because cognitive impairment is very common and
interferes with the overall quality of life in MS patient. Until now, there is
no treatment available for cognitive impairment and vitamin D supplementation
might provide a cheap and safe preventive agent/ treatment. Therefore,
identifying cognitive impairment as a potential target of vitamin D therapy
could warrant inclusion of this parameter as outcome measure in clinical
trials.
Study objective
Primairy objective:
* To assess whether a poor vitamin D status in RRMS patients is negatively
associated with cognitive performance in neuropsychological tests (information
processing speed and working memory) and with measures of cognitive
(dys)function on functional MRI (connectivity analysis).
Secondary objectives:
* To assess whether vitamin D status in RRMS patients is negatively associated
with the presence of more severe depressive symptoms.
* To assess whether vitamin D status in RRMS patients is negatively associated
with the presence of anxiety.
* To assess whether vitamin D status in RRMS patients is negatively associated
with the presence of more severe fatigue.
* To assess whether vitamin D status in RRMS patients is negatively associated
with a higher T2 lesion load.
* To assess whether vitamin D status in RRMS patients is negatively associated
with a reduction in total brain volume.
* To assess whether vitamin D status in RRMS patients is negatively associated
with an imbalance of neurotransmitters as measured by MRI spectroscopy.
Tertiary objectives:
* To explore the correlation of vitamin B12 status with the variables presented
above.
* To explore the correlation between all the variables above.
- To explore the correlation between inflammation in serum and depression
score
Study design
This is a two-arm cross-sectional study in which we will selectively include
subjects with a poor (<50 nmol/L; N = 15) and high (>100 nmol/L; N = 15)
vitamin D status (serum 25-hydroxyvitamin D levels).
Study burden and risks
Participating patients will have to participate in neurological examination and
are asked to cooperate with neuropsychological tests. Additionally, they will
have to cooperate with the MRI assessment, in which patients are asked to be as
quiet as possible. This will take approximately 2 hours. Besides that the
assessments can be more or less fatiguing to the patients, there are no risks
of these assessments. Finally, patients will donate blood 1 time. The risks of
a blood donation are a temporary vasovagal reaction or a local haematoma at the
puncture spot.
Postbus 616
6200 MD Maastricht
NL
Postbus 616
6200 MD Maastricht
NL
Listed location countries
Age
Inclusion criteria
- A definite, MRI-confirmed, RRMS (Polman et al., 2005);
- A disease duration since the onset of first symptoms of *5 years;
- An age of 18-50 years;
- Treatment with either IFN-beta (Avonex, Betaferon, Rebif) or Glatiramer Acetate (Copaxone) or no disease modulating drugs (DMD) treatment;
- No exacerbation within 6 weeks prior to assessment;
- Vitamin D supplementation <<=20 *g/d (800 IU/d);
- A serum 25-hydroxyvitamin D (25(OH)D) level available within 1 year prior to inclusion, being either <50 nmol/L OR >100 nmol/L.
Exclusion criteria
- Progressive disease without relapses;
- Treatment with any immune suppressive or immune modulating drug or than IFN-beta or Glatiramer Acetate within 3 months prior to assessment;
- Cognitive dysfunction reported by spouses, family or MS nurses, neurologist or reported by previous neuropsychological research
- Presence of a depression as detected with the HADS (depression score *8;
- Vitamin D supplementation more than 20 *g/d (800 IU/d);
- Severe visual and/or verbal limitations interfering with neuropsychological testing;
- Contraindications for MRI examination.
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 | NL36446.096.11 |