Clinical trial NCT04363684: ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD)
Official title: ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Frontotemporal Lobar Degeneration (FTLD)
Progressive Supranuclear Palsy (PSP)
Corticobasal Degeneration (CBD)
Behavioral Variant Frontotemporal Dementia (bvFTD)
Semantic Variant Primary Progressive Aphasia (svPPA)
Nonfluent Variant Primary Progressive Aphasia (nfvPPA)
FTD With Amyotrophic Lateral Sclerosis (FTD/ALS)
Amyotrophic Lateral Sclerosis
Oligosymptomatic PSP (oPSP)
C9orf72
GRN Related Frontotemporal Dementia
MAPT Gene Mutation
TBK1 Gene Mutation
Oligosymptomatic Progressive Supranuclear Palsy
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: University of California, San Francisco
name: National Institute on Aging (NIA)
name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2020-04-27
Enrollment: 2100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants will have a referring diagnosis of an FTLD clinical syndrome or will be a member of a family with a strong family history of an FTLD syndrome.

Brief summary: ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) represents the formalized integration of ARTFL (U54 NS092089; funded through 2019) and LEFFTDS (U01 AG045390; funded through 2019) as a single North American research consortium to study FTLD for 2019 and beyond.

Detailed description: The ARTFL LEFFTDS Longitudinal Frontotemporal Dementia (ALLFTD) study aims to evaluate sporadic (s-) and familial (f-) frontotemporal lobar degeneration (FTLD) patients and asymptomatic family members of f-FTLD patients, characterizing the cohorts longitudinally and informing clinical trial design. The study has two arms: a "longitudinal arm" involving a comprehensive assessment of clinical, functional, imaging, and biofluid data collection annually, and a "biofluid-focused arm" involving limited clinical data to accompany biospecimen collection. For more information: https://www.allftd.org/

Eligibility criteria: Longitudinal Arm Inclusion Criteria

Familial FTLD (f-FTLD) participants (either is acceptable):

* members of families in whom at least one member has a known disease-associated mutation in one of the major genes that cause f-FTLD: MAPT, GRN, C9orf72 (or other rare genes)
* an autosomal dominant family history of a FTLD syndrome (without a known gene) verified by medical record review or well-documented family history including family members with a medical history consistent with FTLD or a related disorder.

Sporadic FTLD (s-FTLD) participants:

Sporadic participants should be symptomatic with no known family history nor a genetic mutation indicating f-FTLD. All sporadic participants must have an FTLD syndrome as a referring diagnosis; those determined by ALLFTD clinicians to have non-FTLD diagnoses will be excluded from longitudinal visits, but their baseline visit will be included in comparative datasets. For inclusion in the longitudinal follow-up, participants should meet research criteria for one of the following FTLD syndromes:

* Progressive Supranuclear Palsy (PSP)
* Semantic variant Primary Progressive Aphasia (svPPA)
* Nonfluent variant Primary Progressive Aphasia (nfvPPA)
* Corticobasal Degeneration (CBD)/Corticobasal Syndrome (CBS)
* Behavioral variant Frontotemporal dementia (bvFTD)
* Frontotemporal Dementia with Amyotrophic Lateral Sclerosis (FTD/ALS)

Biofluid-Focused Arm Inclusion Criteria

Participants enrolled in the biofluid arm may be either f-FTLD or s-FTLD. All general inclusion criteria apply. Participants should meet research criteria (as specified above) for any FTLD syndrome or meet familial FTLD inclusion criteria. Because the biofluid arm participants do not undergo the same detailed clinical and functional assessments required for the longitudinal arm, participants may be included regardless of primary language, as long as an appropriately translated consent is available.

Exclusion Criteria:

* Known presence of a structural brain lesion (e.g. tumor, cortical infarct) that could reasonably explain symptoms in a symptomatic participant.
* Known presence of an Alzheimer's disease causing mutation in PSEN1, PSEN2 or APP; or biomarker evidence for Alzheimer's disease as a cause of the clinical syndrome.
* A previous history of Korsakoff encephalopathy, severe alcohol dependence (within 5 years of onset of dementia), frequent alcohol or other substance intoxication, or other neurological disorder.
* Evidence through history or laboratory testing of uncorrected B12 deficiency (B12 \< 95% of local laboratory's normal value), unregulated hypothyroidism (TSH \>150% of normal), HIV positive, renal failure (creatinine \> 2), liver failure (ALT or AST \> two times normal), respiratory failure that requires supplemental oxygen, large confluent white matter lesions, significant systemic medical illnesses such as deteriorating cardiovascular disease.
* Current medication likely to affect CNS functions in the opinion of the site PI.
* In the site investigator's opinion, the participant cannot complete sufficient key study procedures. The participant may be enrolled into the biofluid-focused arm if they can tolerate a blood draw and short clinical exam, but must be able to complete at least 75% of study procedures for enrollment into the longitudinal arm.

Primary outcomes:
measure: Change in Brain Volumes
timeFrame: Baseline, 1 Year, 2 Year, 3 Year, 4 Year, 5 Year
measure: Change in NIH Examiner Executive Composite Score
timeFrame: Baseline, 1 Year, 2 Year, 3 Year, 4 Year, 5 Year
measure: Change in Multidomain Impairment Rating (MIR) Scale
timeFrame: Baseline, 1 Year, 2 Year, 3 Year, 4 Year, 5 Year
Secondary outcomes:
measure: Plasma Neurofilament Light Chain Analysis
timeFrame: 5 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Denver
country: United States
facility: University of Colorado Denver
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Bethesda
country: United States
facility: NIH
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washinton University in St. Louis
state: Missouri
city: Las Vegas
country: United States
facility: Cleveland Clinic Lou Ruvo Center for Brain Health
state: Nevada
city: New York City
country: United States
facility: Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina, Chapel Hill
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Houston
country: United States
facility: Nantz National Alzheimer Center Houston
state: Texas
city: San Antonio
country: United States
facility: UT San Antonio Health Science Center
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
city: Toronto
country: Canada
facility: University of Toronto
state: Ontario
Study officials:
affiliation: Mayo Clinic
name: Bradley Boeve, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: Adam Boxer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: Howie Rosen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tipton PW, Deutschlaender AB, Savica R, Heckman MG, Brushaber DE, Dickerson BC, Gavrilova RH, Geschwind DH, Ghoshal N, Graff-Radford J, Graff-Radford NR, Grossman M, Hsiung GR, Huey ED, Irwin DJ, Jones DT, Knopman DS, McGinnis SM, Rademakers R, Ramos EM, Forsberg LK, Heuer HW, Onyike C, Tartaglia C, Domoto-Reilly K, Roberson ED, Mendez MF, Litvan I, Appleby BS, Grant I, Kaufer D, Boxer AL, Rosen HJ, Boeve BF, Wszolek ZK; ALLFTD Consortium. Differences in Motor Features of C9orf72, MAPT, or GRN Variant Carriers With Familial Frontotemporal Lobar Degeneration. Neurology. 2022 Sep 13;99(11):e1154-e1167. doi: 10.1212/WNL.0000000000200860. Epub 2022 Jul 5.