Multiple Sclerosis (MS). And specifically cognitive problems in MS.
Conditions
Interventions
Product Name: [11C]flumazenil
Pharmaceutical Form: Solution for injection in administration system
Sponsors
VU University medical center Amsterdam
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To participate in the MRI part of the study: - Clinically definite Relapsing Remitting or Secondary Progressive Multiple sclerosis - Sufficient visual acuity and motor performance to perform the MRI task - Between 18 and 60 years of age To participate in the PET-part of the study: - Minimum hemoglobin values of 8 g/dl for men and 7 g/dl for women Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 75 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: For the MRI-part of the study: - MR contraindications - Neurological and/or psychiatric disorders (other than MS) - For MS patients: the use of corticosteroids in the 4 weeks prior to inclusion. For the PET-part of the study: - benzodiazepine use or other drug use that affects the benzodiazepine receptor system (e.g. antipsychotics that show strong binding to GABAA receptors) 4 weeks or less before the start of the study. - In the case of pregnancy or breastfeeding - Insufficient haemoglobin value values as discussed in the inclusion criteria. - (a history of) significant cardiac disease - exposure to previous radiation leading to an annual cumulative dose of more than 10mSv
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of this study is to investigate if the occurrence of cognitive impairment and functional reorganization in MS can be explained by changes in GABA and glutamate concentration and GABAA receptor binding. The levels of GABA and glutamate will be measured with Magnetic Resonance Spectroscopy and the binding of GABAA receptors will be assessed with Positron Emission Tomography. ;Secondary Objective: 2a. To investigate whether cognitively preserved (CP) and impaired (CI) MS patients differ on levels of glutamate (as measured with MRS). 2b. To investigate whether the MS patients with and without cognitive impairment differ on levels of GABA (as measured with MRS). 2c. To investigate whether the MS patients with and without cognitive impairment differ on levels of GABAA receptor binding (as measured with [11C]-flumazenil PET). 3. To investigate whether functional reorganization can be explained by the characteristics of the glutamate and GABA systems as described above. 4. To investigate the relationship between the characteristics of the GABAergic and glutamatergic systems and functional connectivity. ;Primary end point(s): The primary end point of this study is a significant difference in levels of GABA, glutamate and GABAA receptors between healthy controls and cognitively preserved and impaired MS patients. More specifically, we expect differences in the levels of GABA and glutamate in the thalamus and hippocampus and levels of GABAA receptors in the grey matter between the study groups. ;Timepoint(s) of evaluation of this end point: There is only one time of measurement in this cross-sectional study. Therefore, there is no timepoint of evaluation of the end point. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): A secondary end point is a significant correlation between the characteristics of the GABAergic and glutamatergic system as described above and levels of functional activation. More specfically, we investigate hippocampal activation during a memory task (using fMRI) and expect the level of the BOLD-signal to be related to the levels of GABA, glutamate and GABAA receptors. ;Timepoint(s) of evaluation of this end point: There is only one time of measurement in this cross-sectional study. Therefore, there is no timepoint of evaluation of the end point. | — |
Countries
Netherlands
Contacts
Public ContactMarijn Huiskamp
VU University medical center
Outcome results
None listed