E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Frontotemporal dementia (FTD), including symptomatic patients and presymptomatic individuals with genetic mutations predisposing to FTD at a later stage in life. |
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E.1.1.1 | Medical condition in easily understood language |
Frontotemporal dementia |
Frontotemporale dementie |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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.
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E.2.2 | Secondary objectives of the trial |
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). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
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E.4 | Principal 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 |
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E.5 End points |
E.5.1 | 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. |
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E.5.1.1 | 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. |
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E.5.2 | 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 |
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E.5.2.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |