Clinical trial NCT02365922: Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL)
Official title: Rare Diseases Clinical Research Network Advancing Research and Treatment for Frontotemporal Lobar Degeneration [ARTFL]: Research Projects 1 & 2
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: FTLD
Progressive Supranuclear Palsy (PSP)
Frontotemporal Dementia (FTD)
Corticobasal Degeneration (CBD)
PPA Syndrome
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 (ALS)
Oligosymptomatic PSP (oPSP)
Corticobasal Syndrome (CBS)
Keywords: FTLD, PSP, CBD, PPA, FTD, FTD-ALS, CBS, ALS, svPPA, nfvPPA, oPSP
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Center for Advancing Translational Sciences (NCATS)
name: National Institute of Neurological Disorders and Stroke (NINDS)
name: The Bluefield Project to Cure Frontotemporal Dementia
name: Tau Consortium
First posted: 2015-02-19
Enrollment: 1489
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with a diagnosis of a frontotemporal lobar degeneration (FTLD) syndrome, including progressive supranuclear palsy (PSP), semantic variant primary progressive aphasia (svPPA), and frontotemporal dementia with amyotrophic lateral sclerosis (FTD-ALS). Family members of patients with FTLD syndromes.

Brief summary: Frontotemporal Lobar Degeneration (FTLD) is the neuropathological term for a collection of rare neurodegenerative diseases that correspond to four main overlapping clinical syndromes: frontotemporal dementia (FTD), primary progressive aphasia (PPA), corticobasal degeneration syndrome (CBS) and progressive supranuclear palsy syndrome (PSPS). The goal of this study is to build a FTLD clinical research consortium to support the development of FTLD therapies for new clinical trials. The consortium, referred to as Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL), will be headquartered at UCSF and will partner with six patient advocacy groups to manage the consortium. Participants will be evaluated at 14 clinical sites throughout North America and a genetics core will genotype all individuals for FTLD associated genes.

Detailed description: Frontotemporal Lobar Degeneration (FTLD) is the neuropathological term for a collection of rare neurodegenerative diseases that correspond to four main overlapping clinical syndromes: frontotemporal dementia (FTD), primary progressive aphasia (PPA), corticobasal degeneration syndrome (CBS) and progressive supranuclear palsy syndrome (PSPS). The goal of this study is to build a FTLD clinical research consortium (FTLD CRC) to support the development of FTLD therapies for new clinical trials. The FTLD CRC will be headquartered at UCSF and will partner with six patient advocacy groups to manage the consortium. Patients will be evaluated at 13 clinical sites throughout North America and a genetics core will genotype all individuals for FTLD associated genes.

The study will be divided into 2 projects. The first project will be Preparing for Sporadic FTLD Clinical Trials and the second project will be a Longitudinal Assessment of Familial FTLD. Self-registration for an online registry will be available for patients and families with any FTLD syndrome. Eligible participants for research Projects 1 and 2 FTLD will be invited to a CRC site for clinical evaluations. All enrolled participants in both research projects will have a site visit consisting of a neurological exam, medical and family history, cognitive testing, and a blood draw.

Participants in Project 1 who have a diagnosis of Progressive Supranuclear Palsy Syndrome will have two additional assessments. A lumbar puncture (LP) will be performed for CSF collection, and an MRI scan of the brain will be done.

Participants in Project 2: Longitudinal Assessment of familial FTLD will return for a follow-up visit in 12 months; procedures at the follow-up visit will be identical to those at baseline. Additionally, asymptomatic participants will undergo MRI scans at both visits.

Eligibility criteria: 1. Inclusion Criteria:Must meet one of the following research diagnostic criteria for a Frontotemporal lobar degeneration (FTLD) syndrome: behavioral variant frontotemporal dementia (bvFTD), primary progressive aphasia (PPA), semantic variant primary progressive aphasia (svPPA), nonfluent variant primary progressive aphasia (nfvPPA), frontotemporal dementia with amyotrophic lateral sclerosis (FTD/ALS), amyotrophic lateral sclerosis alone, corticobasal syndrome (CBS), progressive supranuclear palsy (PSP) or oligosymptomatic PSP (oPSP), or have a strong family history of FTLD syndromes.
2. Between 18 and 85 (inclusive) years of age.
3. Able to walk (with assistance) at the time of enrollment.
4. Have a reliable study partner who can provide an independent evaluation of functioning.
5. Speak English or Spanish
6. Have Mini Mental State Exam (MMSE) scores between 15 - 30 (inclusive).

Exclusion Criteria:

1. Known presence of a structural brain lesion (e.g. tumor,cortical infarct) that could reasonably explain symptoms in a symptomatic participant without a known f-FTLD causing mutation.
2. Known presence of an Alzheimer's disease causing mutation in PSEN1, PSEN2 or APP; or neuropathological evidence for Alzheimer's disease as a cause of syndrome (from brain biopsy).
3. 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 (such as multiple sclerosis)
4. Evidence through history or laboratory testing of B12 deficiency (B12 \< 95% of local laboratory's normal value), hypothyroidism (TSH \>150% of normal), HIV positive,renal failure (creatinine \> 2), liver failure (ALT or AST \> two times normal), respiratory failure (requiring oxygen), extra-axial brain tumor (with visible compression of the brain parenchyma), large cerebral infarct that could account for clinical syndrome, large confluent white matter lesions (grades 3 or 4, \[107\] significant systemic medical illnesses such as deteriorating cardiovascular disease;
5. Current medication likely to affect CNS functions in the opinion of the site PI: long acting benzodiazepines such as diazepam (short-acting benzodiazepines are OK), non-SSRI antidepressants (SSRIs or trazodone are OK), no lithium, typical neuroleptics as listed in the Manual of Procedures, narcotics (codeine is OK, but hold 24 hours before neuropsychological testing), anticonvulsants (outside of therapeutic ranges), antihistamines (if taking greater than three times per week; hold 24 hours before neuropsychological testing).
6. In the site investigator's opinion, the participant cannot complete sufficient key study procedures, or equivalent assessment of impairment level.
7. For groups where MRI scans are planned procedures, any contraindication for MRI scanning, such as pacemaker or other implanted metals.

Primary outcomes:
measure: Scores of UDS FTLD Module Tests
timeFrame: Baseline, 12 mo.
Secondary outcomes:
measure: Progressive Supranuclear Palsy Rating Scale (PSPRS)
timeFrame: Baseline
measure: Neuroimaging
timeFrame: Baseline; 12 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
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: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Charlestown
country: United States
facility: Harvard University Massachusetts General Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: Columbia University
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve University Hospitals Cleveland Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Seattle
country: United States
facility: University of Washington Harborview Medical Center
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: Study PI
name: Adam L Boxer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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