Neurofilament Surveillance Project (NSP)

Frontotemporal Dementia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04516499
• Other study ID #: NSP001
• Status: Active, not recruiting
• Start date: September 2, 2020
• Est. completion date: December 2026

Study information

• Verified date: November 2023
• Source: The Bluefield Project to Cure Frontotemporal Dementia
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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/.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 335
• Est. completion date: December 2026
• Est. primary completion date: December 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Aphasia, Primary Progressive
• Frontotemporal Dementia
• Frontotemporal Lobar Degeneration
• FTD-GRN
• Pick Disease of the Brain

Locations

Country	Name	City	State
United States	Johns Hopkins University School of Medicine	Baltimore	Maryland
United States	Massachusetts General Hospital	Charlestown	Massachusetts
United States	Mayo Clinic Florida	Jacksonville	Florida
United States	Columbia University	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University in St. Louis	Saint Louis	Missouri
United States	University of California, San Francisco	San Francisco	California

Sponsors (3)

Lead Sponsor	Collaborator
The Bluefield Project to Cure Frontotemporal Dementia	Mayo Clinic, University of California, San Francisco

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Clinical and MRI correlates	To evaluate ALLFTD collected clinical and magnetic resonance imaging (MRI) neuroimaging correlates with plasma NfL levels in asymptomatic and symptomatic f-FTLD mutation carriers	36 months
Other	Other biomarker evaluation	To measure other novel blood biomarkers of neurodegeneration yet to be determined	36 months
Primary	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	Intersubject variability of plasma NfL measurements	Concentration of plasma neurofilament light chain protein	36 months
Secondary	Logistics measure	Participant compliance with scheduled remote blood collection and sample processing	36 months