Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Neurofilament Surveillance Project (NSP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04516499
Recruitment Status : Recruiting
First Posted : August 18, 2020
Last Update Posted : May 24, 2021
Sponsor:
Collaborators:
Mayo Clinic
University of California, San Francisco
Information provided by (Responsible Party):
The Bluefield Project to Cure Frontotemporal Dementia

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/.

Condition or disease
Frontotemporal Dementia Frontotemporal Lobar Degeneration 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.

Layout table for study information
Study Type : Observational
Estimated Enrollment : 335 participants
Observational Model: Family-Based
Time Perspective: Prospective
Official Title: Remote Blood Biomarker Monitoring in Frontotemporal Lobar Degeneration: Neurofilament Surveillance Project (NSP)
Actual Study Start Date : September 2, 2020
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : December 2024


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.



Primary Outcome Measures :
  1. Neurofilament Light Chain Levels [ Time Frame: 36 months ]
    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


Secondary Outcome Measures :
  1. Intersubject variability of plasma NfL measurements [ Time Frame: 36 months ]
    Concentration of plasma neurofilament light chain protein

  2. Logistics measure [ Time Frame: 36 months ]
    Participant compliance with scheduled remote blood collection and sample processing


Other Outcome Measures:
  1. Clinical and MRI correlates [ Time Frame: 36 months ]
    To evaluate ALLFTD collected clinical and magnetic resonance imaging (MRI) neuroimaging correlates with plasma NfL levels in asymptomatic and symptomatic f-FTLD mutation carriers

  2. Other biomarker evaluation [ Time Frame: 36 months ]
    To measure other novel blood biomarkers of neurodegeneration yet to be determined


Biospecimen Retention:   Samples With DNA
Plasma will be extracted from participant's whole blood. The plasma will be analyzed for the levels of neurofilament light chain and other potential biomarkers.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04516499


Contacts
Layout table for location contacts
Contact: Rachel Acuna-Narvaez 6503801191 rachel.acuna-narvaez@bluefieldproject.org

Locations
Layout table for location information
United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States, 94158
Contact: Lynn Bajorek    415-476-2936    Lynn.Bajorek@ucsf.edu   
Principal Investigator: Adam Boxer, MD, PhD         
Principal Investigator: Howie Rosen, MD         
United States, Florida
Mayo Clinic Florida Recruiting
Jacksonville, Florida, United States, 32224
Contact: Ana Reineke    904-953-4107    Reineke.Maricica@mayo.edu   
Principal Investigator: Neill Graff-Radford, MBChB         
United States, Maryland
Johns Hopkins University School of Medicine Recruiting
Baltimore, Maryland, United States, 21287
Contact: Ann Fishman    410-502-5816    ann.fishman@jhu.edu   
Principal Investigator: Chiadi Onyike, MD, MHS         
United States, Massachusetts
Massachusetts General Hospital Not yet recruiting
Charlestown, Massachusetts, United States, 02129
Contact: Site Coordinator       ekrahn@mgh.harvard.edu   
Principal Investigator: Brad Dickerson, MD         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Tyler Kolander    507-284-9295    Kolander.Tyler@mayo.edu   
Principal Investigator: Bradley Boeve, MD         
United States, Missouri
Washington University in St. Louis Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Tina Nolte       nolte.tina@wustl.edu   
Principal Investigator: Nupur Ghoshal, MD, PhD         
United States, New York
Columbia University Not yet recruiting
New York, New York, United States, 10032
Contact: Masood Manoochehri    212-305-5710    mm2626@cumc.columbia.edu   
Principal Investigator: Edward Huey, MD         
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Study Coordinator       erica.howard@uphs.upenn.edu   
Principal Investigator: Murray Grossman, MD         
Sponsors and Collaborators
The Bluefield Project to Cure Frontotemporal Dementia
Mayo Clinic
University of California, San Francisco
Investigators
Layout table for investigator information
Principal Investigator: Adam Boxer, MD, PhD University of California, San Francisco
Principal Investigator: Bradley Boeve, MD Mayo Clinic
Principal Investigator: Howie Rosen, MD University of California, San Francisco
Study Director: Laura Mitic, PhD The Bluefield Project to Cure Frontotemporal Dementia
Layout table for additonal information
Responsible Party: The Bluefield Project to Cure Frontotemporal Dementia
ClinicalTrials.gov Identifier: NCT04516499    
Other Study ID Numbers: NSP001
First Posted: August 18, 2020    Key Record Dates
Last Update Posted: May 24, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Please consult with ALLFTD regarding individual participant data.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by The Bluefield Project to Cure Frontotemporal Dementia:
C9orf72
GRN
MAPT
Additional relevant MeSH terms:
Layout table for MeSH terms
Frontotemporal Dementia
Aphasia, Primary Progressive
Pick Disease of the Brain
Frontotemporal Lobar Degeneration
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
TDP-43 Proteinopathies
Neurodegenerative Diseases
Proteostasis Deficiencies
Metabolic Diseases
Aphasia
Speech Disorders
Language Disorders
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations