Neurofilament Surveillance Project (NSP)

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

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/.

Study Overview

• Status: Active, not recruiting
• Conditions: Frontotemporal Dementia; Frontotemporal Lobar Degeneration; FTD; FTLD; FTD-GRN

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.

• Study Type: Observational
• Enrollment (Actual): 342

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94158
      • University of California, San Francisco
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Florida
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University School of Medicine
  • Massachusetts
    • Charlestown, Massachusetts, United States, 02129
      • Massachusetts General Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University in St. Louis
  • New York
    • New York, New York, United States, 10032
      • Columbia University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 81 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• 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.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Family-Based
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
f-FTLD mutation carriers; 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; 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?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 biomarker evaluation	To measure other novel blood biomarkers of neurodegeneration yet to be determined	36 months

Collaborators and Investigators

• Sponsor: The Bluefield Project to Cure Frontotemporal Dementia
• Collaborators: Mayo Clinic; University of California, San Francisco
• Investigators: Principal Investigator: Adam Boxer, MD, PhD, University of California, San Francisco; Principal Investigator: Howie Rosen, MD, University of California, San Francisco; Study Director: Laura Mitic, PhD, The Bluefield Project to Cure Frontotemporal Dementia; Principal Investigator: Bradley Boeve, MD, Mayo Clinic

Publications and helpful links

General Publications

• Saracino D, Dorgham K, Camuzat A, Rinaldi D, Rametti-Lacroux A, Houot M, Clot F, Martin-Hardy P, Jornea L, Azuar C, Migliaccio R, Pasquier F, Couratier P, Auriacombe S, Sauvee M, Boutoleau-Bretonniere C, Pariente J, Didic M, Hannequin D, Wallon D; French Research Network on FTD/FTD-ALS; PREV-DEMALS and Predict-PGRN study groups; Colliot O, Dubois B, Brice A, Levy R, Forlani S, Le Ber I. Plasma NfL levels and longitudinal change rates in C9orf72 and GRN-associated diseases: from tailored references to clinical applications. J Neurol Neurosurg Psychiatry. 2021 Dec;92(12):1278-1288. doi: 10.1136/jnnp-2021-326914. Epub 2021 Aug 4.
• Wilke C, Reich S, van Swieten JC, Borroni B, Sanchez-Valle R, Moreno F, Laforce R, Graff C, Galimberti D, Rowe JB, Masellis M, Tartaglia MC, Finger E, Vandenberghe R, de Mendonca A, Tagliavini F, Santana I, Ducharme S, Butler CR, Gerhard A, Levin J, Danek A, Otto M, Frisoni G, Ghidoni R, Sorbi S, Bocchetta M, Todd E, Kuhle J, Barro C; Genetic Frontotemporal dementia Initiative (GENFI); Rohrer JD, Synofzik M. Stratifying the Presymptomatic Phase of Genetic Frontotemporal Dementia by Serum NfL and pNfH: A Longitudinal Multicentre Study. Ann Neurol. 2022 Jan;91(1):33-47. doi: 10.1002/ana.26265. Epub 2021 Nov 29.
• Rojas JC, Wang P, Staffaroni AM, Heller C, Cobigo Y, Wolf A, Goh SM, Ljubenkov PA, Heuer HW, Fong JC, Taylor JB, Veras E, Song L, Jeromin A, Hanlon D, Yu L, Khinikar A, Sivasankaran R, Kieloch A, Valentin MA, Karydas AM, Mitic LL, Pearlman R, Kornak J, Kramer JH, Miller BL, Kantarci K, Knopman DS, Graff-Radford N, Petrucelli L, Rademakers R, Irwin DJ, Grossman M, Ramos EM, Coppola G, Mendez MF, Bordelon Y, Dickerson BC, Ghoshal N, Huey ED, Mackenzie IR, Appleby BS, Domoto-Reilly K, Hsiung GR, Toga AW, Weintraub S, Kaufer DI, Kerwin D, Litvan I, Onyike CU, Pantelyat A, Roberson ED, Tartaglia MC, Foroud T, Chen W, Czerkowicz J, Graham DL, van Swieten JC, Borroni B, Sanchez-Valle R, Moreno F, Laforce R, Graff C, Synofzik M, Galimberti D, Rowe JB, Masellis M, Finger E, Vandenberghe R, de Mendonca A, Tagliavini F, Santana I, Ducharme S, Butler CR, Gerhard A, Levin J, Danek A, Otto M, Sorbi S, Cash DM, Convery RS, Bocchetta M, Foiani M, Greaves CV, Peakman G, Russell L, Swift I, Todd E, Rohrer JD, Boeve BF, Rosen HJ, Boxer AL; ALLFTD and GENFI consortia. Plasma Neurofilament Light for Prediction of Disease Progression in Familial Frontotemporal Lobar Degeneration. Neurology. 2021 May 4;96(18):e2296-e2312. doi: 10.1212/WNL.0000000000011848. Epub 2021 Apr 7.
• Gendron TF, Heckman MG, White LJ, Veire AM, Pedraza O, Burch AR, Bozoki AC, Dickerson BC, Domoto-Reilly K, Foroud T, Forsberg LK, Galasko DR, Ghoshal N, Graff-Radford NR, Grossman M, Heuer HW, Huey ED, Hsiung GR, Irwin DJ, Kaufer DI, Leger GC, Litvan I, Masdeu JC, Mendez MF, Onyike CU, Pascual B, Ritter A, Roberson ED, Rojas JC, Tartaglia MC, Wszolek ZK, Rosen H, Boeve BF, Boxer AL; ALLFTD consortium; Petrucelli L. Comprehensive cross-sectional and longitudinal analyses of plasma neurofilament light across FTD spectrum disorders. Cell Rep Med. 2022 Apr 19;3(4):100607. doi: 10.1016/j.xcrm.2022.100607. eCollection 2022 Apr 19.

Helpful Links

• ALLFTD is the parent study of the NSP.

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2020
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: August 11, 2020
• First Submitted That Met QC Criteria: August 14, 2020
• First Posted (Actual): August 18, 2020

Study Record Updates

• Last Update Posted (Estimated): October 29, 2025
• Last Update Submitted That Met QC Criteria: October 27, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: C9orf72; GRN; MAPT
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Metabolic Diseases; Neurocognitive Disorders; Dementia; Neurodegenerative Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Nutritional and Metabolic Diseases; Frontotemporal Dementia; Frontotemporal Lobar Degeneration; Frontotemporal Dementia With Motor Neuron Disease
• Other Study ID Numbers: NSP001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Please consult with ALLFTD regarding individual participant data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No