Amyotrophic Lateral Sclerosis, Behavioral Variant Frontotemporal Dementia (bvFTD), C9orf72, Corticobasal Degeneration (CBD), Frontotemporal Lobar Degeneration (FTLD), FTD With Amyotrophic Lateral Sclerosis (FTD/ALS), GRN Related Frontotemporal Dementia, MAPT Gene Mutation, Nonfluent Variant Primary Progressive Aphasia (nfvPPA), Oligosymptomatic Progressive Supranuclear Palsy, Oligosymptomatic PSP (oPSP), Progressive Supranuclear Palsy (PSP), Semantic Variant Primary Progressive Aphasia (svPPA), TBK1 Gene Mutation
Conditions
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/
Interventions
None listed
Sponsors
Mayo Clinic
University of California, San Francisco
National Institute on Aging (NIA)
National Institute of Neurological Disorders and Stroke (NINDS)
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Brain Volumes | Baseline, 1 Year, 2 Year, 3 Year, 4 Year, 5 Year | Compare rates of change in whole brain and regional volumes between asymptomatic f-FTLD and symptomatic f- and s-FTLD, measured using MRI. |
| Change in neuropsychological battery | Baseline, 1 Year, 2 Year, 3 Year, 4 Year, 5 Year | Evaluate change in performance on a neuropsychological battery in asymptomatic f-FTLD as well as symptomatic f-FTLD and s-FTLD. |
| Change in Multidomain Impairment Rating (MIR) Scale | Baseline, 1 Year, 2 Year, 3 Year, 4 Year, 5 Year | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Neurofilament Light Chain Analysis | 5 years | Annual blood samples will be collected to detect changes in plasma neurofilament light chain concentrations |
Countries
Canada, United States
Contacts
CONTACTLeah K Forsberg, PhD
CONTACTHilary Heuer, PhD
PRINCIPAL_INVESTIGATORBradley Boeve, MD
Mayo Clinic
PRINCIPAL_INVESTIGATORAdam Boxer, MD, PhD
University of California, San Francisco
PRINCIPAL_INVESTIGATORHowie Rosen, MD
University of California, San Francisco
Outcome results
None listed