Clinical trial NCT04516499: Neurofilament Surveillance Project (NSP)
Official title: Remote Blood Biomarker Monitoring in Frontotemporal Lobar Degeneration: Neurofilament Surveillance Project (NSP)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Frontotemporal Dementia
Frontotemporal Lobar Degeneration
FTD-GRN
FTD
FTLD
Keywords: C9orf72
GRN
MAPT
Lead sponsor: The Bluefield Project to Cure Frontotemporal Dementia
Sponsor class: OTHER
Collaborators: name: Mayo Clinic
name: University of California, San Francisco
First posted: 2020-08-18
Enrollment: 342
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: FAMILY_BASED
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study is an ancillary study to ALLFTD. Thus, all NSP participants will be recruited directly from the longitudinal arm of ALLFTD.

Roughly equivalent numbers of participants will be enrolled from each of the following groups:

* Members of families with known mutations in C9orf72
* Members of families with known mutations in GRN
* Members of families with known mutations in MAPT

Although participant must be from a family with a known mutation, the participant themselves need not know their personal mutation status.

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Male or female
2. Ages 18-85
3. Provision of signed and dated informed consent form
4. Stated willingness to comply with all study procedures and availability for the duration of the study
5. Is enrolled in the longitudinal arm of ALLFTD
6. Is a member of a family with a known mutation in C9orf72, GRN or MAPT

Exclusion Criteria:

1. Any permanent contra-indication to repeated blood draws, such as poor venous access.
2. Any conditions or circumstances which, in the opinion of the investigator, would not allow participation in the study.

Primary outcomes:
measure: Neurofilament Light Chain Levels
timeFrame: 36 months
Secondary outcomes:
measure: Intersubject variability of plasma NfL measurements
timeFrame: 36 months
measure: Logistics measure
timeFrame: 36 months
Other outcomes:
measure: Clinical and MRI correlates
timeFrame: 36 months
measure: Other biomarker evaluation
timeFrame: 36 months
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Charlestown
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: New York
country: United States
facility: Columbia University
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of California, San Francisco
name: Adam Boxer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic
name: Bradley Boeve, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: Howie Rosen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Bluefield Project to Cure Frontotemporal Dementia
name: Laura Mitic, PhD
role: STUDY_DIRECTOR
References:
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