Imaging of inflammation in the cortex of the brain in progressive MS patients

Conditions: Progressive multiple sclerosis, both primary and secondary progressive
MedDRA version: 17.1Level: PTClassification code 10063401Term: Primary progressive multiple sclerosisSystem Organ Class: 10029205 - Nervous system disorders
MedDRA version: 17.1Level: PTClassification code 10063400Term: Secondary progressive multiple sclerosisSystem Organ Class: 10029205 - Nervous system disorders
MedDRA version: 17.1Level: PTClassification code 10053395Term: Progressive multiple sclerosisSystem Organ Class: 10029205 - Nervous system disorders
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Registration Number: EUCTR2014-002547-17-NL

Lead Sponsor: VU University Medical Center

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: Not specified

Inclusion Criteria

- For the MS patient group: diagnosis primary or secondary progressive MS with EDSS scores 4.0 to 7.5 - 18 to 60 years
- Written informed consent
- No immunomodulating or immunosuppressive treatment in previous three months
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 20
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

- Inability to undergo MRI, e.g. metal objects in or around the body, claustrophobia or inability to lie still in the scanner. For the MS patients: contra-indication for gadolinium administration, e.g. previous allergic reaction to gadolinium.
- Homozygote Ala(147)Thr genotype (low-affinity binders)
- Significant immune disease other than MS
- (History of) other relevant neurological disease
- History of malignancy
- Known significant cardiac disease
- Inadequate renal function: creatinine clearance <60 ml/min
- Loss or donation of blood over 500 mL within four months prior to screening.
- In male subjects Hb < 8.0 g/dL, in female subjects Hb < 7.0 g/dL
- Pregnant or breast feeding
- (History of) alcohol and/or drug abuse
- Exposure to previous radiation leading to annual cumulative dose of more than 10 mSV if participating in this protocol
- Use of benzodiazepines within 1 week of the PET scan

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The aim of this pilot study is to determine whether uptake op the TSPO radioligand [18f}DPA-714 can be quantified in the cortex and/or hippocampus in vivo to discriminate progressive MS patients from controls.;Secondary Objective: Secondarily we will determine whether:<br>1. Labeled microglial cells co-localize with MRI detected GML and cortical thinning.<br>2. Binding in cortex and/or hippocampus correlates with clinical disability and cognitive decline in progressive MS patients.;Primary end point(s): The main study parameter is the [18F]DPA-714 binding potential (BP) which will be assessed in PPMS and SPMS patients and healthy control subjects with validated tracer kinetic models. BP is a measurement of microglial activation.;Timepoint(s) of evaluation of this end point: The BP will be assessed from the data collected during the 60 minute [18F]DPA-714 PET scan. Each patient and control subject will undergo one PET scan and therefore one administration of the tracer.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - The relation between [18F]DPA-714 BP in the cerebral cortex and/or hippocampus and MRI detected grey matter lesions and cortical thinning.<br>- The relation between [18F]DPA-714 BP in the cerebral cortex and/or hippocampus and clinical disability and cognitive decline in progressive MS patients as measured with the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC) and Symbol Digit Modalities Test (SDMT).;Timepoint(s) of evaluation of this end point: Each patient and control will have three visits in a fixt order: 1. screening session 2. MRI scan 3. PET scan.<br>The end points will be evaluated after completion of these three visits.