ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD)

Amyotrophic Lateral Sclerosis Clinical Trial

Official title:

ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04363684
• Other study ID #: 19-004543
• Secondary ID: U19AG063911
• Status: Recruiting
• Start date: March 1, 2020
• Est. completion date: June 2025

Study information

• Verified date: March 2024
• Source: Mayo Clinic
• Contact: Leah K Forsberg, PhD
• Phone: 507-293-9577
• Email: forsberg.leah[@]mayo.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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/

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2100
• Est. completion date: June 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Aphasia
• Aphasia, Primary Progressive
• Behavioral Variant Frontotemporal Dementia (bvFTD)
• Corticobasal Degeneration
• Corticobasal Degeneration (CBD)
• Dementia
• Frontotemporal Dementia
• Frontotemporal Lobar Degeneration
• Frontotemporal Lobar Degeneration (FTLD)
• FTD With Amyotrophic Lateral Sclerosis (FTD/ALS)
• GRN Related Frontotemporal Dementia
• Motor Neuron Disease
• Nonfluent Variant Primary Progressive Aphasia (nfvPPA)
• Oligosymptomatic PSP (oPSP)
• Pick Disease of the Brain
• Progressive Supranuclear Palsy (PSP)
• Sclerosis
• Semantic Variant Primary Progressive Aphasia (svPPA)
• Supranuclear Palsy, Progressive

Locations

Country	Name	City	State
Canada	University of Toronto	Toronto	Ontario
Canada	University of British Columbia	Vancouver	British Columbia
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	Johns Hopkins University	Baltimore	Maryland
United States	NIH	Bethesda	Maryland
United States	University of Alabama Birmingham	Birmingham	Alabama
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of North Carolina, Chapel Hill	Chapel Hill	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	Case Western Reserve Medical Center	Cleveland	Ohio
United States	University of Colorado Denver	Denver	Colorado
United States	Nantz National Alzheimer Center Houston	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	Mayo Clinic Florida	Jacksonville	Florida
United States	Cleveland Clinic Lou Ruvo Center for Brain Health	Las Vegas	Nevada
United States	University of California, Los Angeles	Los Angeles	California
United States	Vanderbilt University	Nashville	Tennessee
United States	Columbia Unversity	New York	New York
United States	Mount Sinai	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	Washinton University in St. Louis	Saint Louis	Missouri
United States	UT San Antonio Health Science Center	San Antonio	Texas
United States	University of California, San Diego	San Diego	California
United States	University of California San Francisco	San Francisco	California
United States	University of Washington	Seattle	Washington

Sponsors (4)

Lead Sponsor	Collaborator
Mayo Clinic	National Institute of Neurological Disorders and Stroke (NINDS), National Institute on Aging (NIA), University of California, San Francisco

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Brain Volumes	Compare rates of change in whole brain and regional volumes between asymptomatic f-FTLD and symptomatic f- and s-FTLD, measured using MRI.	Baseline, 1 Year, 2 Year, 3 Year, 4 Year, 5 Year
Primary	Change in NIH Examiner Executive Composite Score	Evaluate change in NIH Examiner Executive Composite Score in asymptomatic f-FTLD.	Baseline, 1 Year, 2 Year, 3 Year, 4 Year, 5 Year
Primary	Change in Multidomain Impairment Rating (MIR) Scale	Annual change in MIR score (total score 0-3), which is a new global scale for FTLD that incorporates behavioral, cognitive, and motor dysfunction in the rating.	Baseline, 1 Year, 2 Year, 3 Year, 4 Year, 5 Year
Secondary	Plasma Neurofilament Light Chain Analysis	Annual blood samples will be collected to detect changes in plasma neurofilament light chain concentrations	5 years

External Links

•   ALLFTD Study Website