Neurofilament Surveillance Project (NSP)

Study Overview
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Brief Summary
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This is a biomarker study designed to collect and analyze blood specimens from individuals carrying known familial frontotemporal lobar degeneration (f-FTLD) mutations compared to a control group of individuals without known f-FTLD mutations. The NSP is an ancillary study to the ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study, NCT04363684. More information can be found at https://www.allftd.org/.

Detailed Description
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Frontotemporal Lobar Degeneration (FTLD), a group of clinically heterogeneous neurodegenerative diseases characterized by progressive deterioration of the frontal and temporal cortices as well as basal ganglia and brainstem structures, is a common cause of neurodegenerative dementia in people who are less than 60 years old at onset. It is uniformly fatal. FTLD is a rare disease, with an estimated prevalence of approximately 5-22 per 100,000. There are no approved treatments, however several investigational agents are in human trials and a variety of novel agents are poised to enter human development. Experience from other neurodegenerative diseases suggests that potential disease modifying treatments are most likely to be efficacious if initiated before the onset of symptoms. Approximately 25% of FTLD cases are familial (f-FTLD) and due to autosomal dominant mutations in one of three genes: C9orf72, progranulin (GRN) or microtubule associated protein tau (MAPT). Many of the new therapies entering the clinic directly target one of these genetic causes and raise the possibility that the clinical features of FTLD could be delayed or prevented in these individuals if an efficacious therapy was initiated prior to the onset of symptoms. The major barrier to determining efficacy of novel therapeutic agents for f-FTLD in such prevention trials is the lack of an endpoint that can indicate therapeutic efficacy prior to the onset of symptoms. Our preliminary data strongly suggest that plasma neurofilament light chain (NfL) could serve as such a biomarker. This non-interventional study is in preparation for pivotal clinical trials. Up to 335 participants will provide blood remotely via visits from traveling mobile research nurses four times a year for three years (4355 samples total) to enable the observation of peripheral NfL levels longitudinally during disease onset and progression, with the ultimate goal of qualifying plasma NfL as an endpoint for f-FTLD prevention trials. The NSP study is an ancillary study to ALLFTD, and biomarker data collected in the NSP will be correlated with ALLFTD clinical data. More information on the NSP study may be found at https://www.allftd.org/nsp.

Official Title
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Remote Blood Biomarker Monitoring in Frontotemporal Lobar Degeneration: Neurofilament Surveillance Project (NSP)

Conditions
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Frontotemporal Lobar Degeneration, FTD-GRN, Frontotemporal Dementia

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female Ages 18-85 Provision of signed and dated informed consent form Stated willingness to comply with all study procedures and availability for the duration of the study Is enrolled in the longitudinal arm of ALLFTD Is a member of a family with a known mutation in C9orf72, GRN or MAPT Exclusion Criteria: Any permanent contra-indication to repeated blood draws, such as poor venous access. Any conditions or circumstances which, in the opinion of the investigator, would not allow participation in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| f-FTLD mutation carriers<br>All participants must be from a family with f-FTLD mutations. The f-FTLD mutation carrier group members will have their genetic status tested and included in this group if a f-FTLD mutation is observed. Participants do not need to know or be told their genetic status. | |
| Non-mutation carriers from families with f-FTLD mutations<br>All participants must be from a family with f-FTLD mutations. The non-mutation carrier group members will have their genetic status tested and included in this group if they do not have a f-FTLD mutation. Participants do not need to know or be told their genetic status. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurofilament Light Chain Levels | To determine the longitudinal stability of plasma neurofilament light chain (NfL) measured every 3 months for 36 months in individuals at-risk for symptomatic FTLD | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intersubject variability of plasma NfL measurements | Concentration of plasma neurofilament light chain protein | 36 months | 
| Logistics measure | Participant compliance with scheduled remote blood collection and sample processing | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MAPT, C9orf72, GRN