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

• Register: EUCTR
• Last refreshed on: 14 March 2016
• Main ID: EUCTR2014-002547-17-NL
• Date of registration: 01/12/2014
• Prospective Registration: Yes
• Primary sponsor: VU University Medical Center
• Public title: Imaging of inflammation in the cortex of the brain in progressive MS patients
• Scientific title: Grey matter microglial imaging with [18F]DPA-714 in progressive MS patients - [18F]DPA-714 PET in MS
• Date of first enrolment: 18/12/2014
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-002547-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Netherlands

Contacts

• Name: Coordinating investigator
• Affiliation: VU University Medical Center

• Name: Coordinating investigator
• Affiliation: VU University Medical Center

Key inclusion & exclusion criteria

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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Progressive multiple sclerosis, both primary and secondary progressive
MedDRA version: 17.1 Level: PT Classification code 10063401 Term: Primary progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 17.1 Level: PT Classification code 10063400 Term: Secondary progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 17.1 Level: PT Classification code 10053395 Term: Progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Product Name: [18F]DPA-714
Pharmaceutical Form: Radiopharmaceutical precursor
INN or Proposed INN: [18F]DPA-714
Other descriptive name: [18F]DPA-714
Concentration unit: MBq megabecquerel(s)
Concentration type: equal
Concentration number: 250-

Primary Outcome(s)

Secondary Objective: Secondarily we will determine whether:
1. Labeled microglial cells co-localize with MRI detected GML and cortical thinning.
2. Binding in cortex and/or hippocampus correlates with clinical disability and cognitive decline in progressive MS patients.

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.

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.

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.

Secondary Outcome(s)

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.
The end points will be evaluated after completion of these three visits.

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.
- 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).

Secondary ID(s)

VU-49636

Source(s) of Monetary Support

VU University Medical Center