Frontotemporal dementia (FTD), including symptomatic patients and presymptomatic individuals with genetic mutations predisposing to FTD at a later stage in life.
Conditions
Interventions
Product Name: [18F]DPA-714
Pharmaceutical Form: Radiopharmaceutical precursor
INN or Proposed INN: [18F]DPA-714
Other descriptive name: [18-F]DPA-714
Concentration unit: MBq megabecquerel(s)
Concentra
Sponsors
Erasmus Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Able to tolerate the [18F]DPA-714 PET-MRI scan procedures and to make an informed decision to participate in this study - Symptomatic patients must meet clinical criteria for FTD clinical syndromes - Presymptomatic individuals and healthy controls must show no objective evidence of cognitive impairment 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 27 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: - Has contraindications for MRI scanning, e.g. metal objects in the body, claustrophobia - Has evidence of structural brain abnormalities that are likely to interfere with the interpretation of PET scan - Has one or more comorbidities that may interfere with the outcomes of the study (e.g. significant immune disease, neurological disease, CNS malignancy) - Has a history of moderate or severe traumatic brain injury - Has made use of immunomodulatory or immunosuppressive therapy in the 3 months prior to the scan - Has any disease or uses medication that may compromise the function of the body systems and could interfere with the metabolism of the radiotracer or the interpretation of the results - Has an unstable medical condition - Is pregnant or breastfeeding - Has a history of severe drug allergy or hypersensitivity - Has been injected with a previously administered radiopharmaceutical within 6 terminal half-lives OR when the total yearly radiation exposure exceeds 10 mSv if participating in this protocol - Is a low-affinity binder for the tracer based on the rs6971 TSPO polymorphism - Has a present or past history of alcohol and/or drug abuse - Makes use of benzodiazepines and is not able to suspend their use during the week prior to the PET scan
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The overarching goal of this pilot study is to test the novel TSPO [18F]DPA-714 tracer as a marker of microglial activation in FTD. Within this framework, our primary objective is to assess the quantity and regional distribution of [18F]DPA-714 binding as a marker of microglial activation in patients with FTD compared to controls. ;Secondary Objective: i. To compare the quantity and regional distribution of [18F]DPA-714 binding in symptomatic and presymptomatic carriers of FTD genetic mutations; ii. To explore the relationship between [18F]DPA-714 binding, clinical presentation and progression, and other markers of neurodegeneration (MRI, CSF/serum biomarkers).;Primary end point(s): The quantity and regional distribution of [18F]DPA-714 binding as a marker of microglial activation in patients with FTD compared to controls. [18F]DPA-714 binding will be measured as standardized uptake value ratios using an unaffected brain region as reference region. ;Timepoint(s) of evaluation of this end point: The primary end point will be evaluated after PET-MRI data collection. Each participant will undergo one single scan and will receive one administration of the radiotracer immediately prior to the scan. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Comparison of [18F]DPA-714 binding between patients and presymptomatic gene carriers - Comparison of [18F]DPA-714 binding between presymptomatic gene carriers and healthy controls (i.e. non-carriers) - Correlation of [18F]DPA-714 binding with other MRI measures of neuroinflammation and neurodegeneration - Correlation of [18F]DPA-714 binding with measures of clinical severity and neuropsychological performance - Correlation of [18F]DPA-714 binding with levels of CSF and/or blood biomarkers;Timepoint(s) of evaluation of this end point: The secondary end points will also be evaluated after PET-MRI data collection. Scanning by means of PET-MRI will enable us to obtain [18F]DPA-714 binding data as well as acquisition of MRI sequences relevant for neuroinflammation and neurodegeneration (T1, T2, T2*, FLAIR, DTI). Clinical and neuropsychological data are available for FTD patients and presymptomatic carriers, who have been seen and/or diagnosed at the Alzheimer Center and are enrolled in ongoing research protocols. In a subset of patients, fluid samples (CSF, blood) are available for parallel analysis of neuroinflammatory markers and correlation with PET-MRI data. | — |
Countries
Netherlands
Contacts
Public ContactPrincipal Investigator
Erasmus Medical Center
Outcome results
None listed