Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL)

NCT02365922 | Completed

• 2 other identifiers: ARTFL81011U54NS092089-01
• Study Type: observational
• Target: 1,489
• Locations: 2 countries
• Sites: 17

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.

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

Outcome Measures

Primary Outcomes (1)

• Scores of UDS FTLD Module Tests

  Neuropsychological test scores from the Uniform Data Set FTLD Module will be collected and compared across patient populations.

  Baseline, 12 mo.

Secondary Outcomes (2)

• Progressive Supranuclear Palsy Rating Scale (PSPRS)

  Baseline

• Neuroimaging

  Baseline; 12 months

Study Arms (1)

Patients with FTLD or family members

Participants with FTLD syndrome diagnoses and/or strong family histories of FTLD.

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• Between 18 and 85 (inclusive) years of age.
• Able to walk (with assistance) at the time of enrollment.
• Have a reliable study partner who can provide an independent evaluation of functioning.
• Speak English or Spanish
• Have Mini Mental State Exam (MMSE) scores between 15 - 30 (inclusive).

You may not qualify if:

• 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.
• 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).
• 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)
• 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;
• 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).
• In the site investigator's opinion, the participant cannot complete sufficient key study procedures, or equivalent assessment of impairment level.
• For groups where MRI scans are planned procedures, any contraindication for MRI scanning, such as pacemaker or other implanted metals.

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Center for Advancing Translational Sciences (NCATS): collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• The Bluefield Project to Cure Frontotemporal Dementia: collaborator
• Tau Consortium: collaborator

Study Sites (17)

University of Alabama

Birmingham, Alabama, 35294, United States

Location

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

University of California, San Diego

San Diego, California, 92037, United States

Location

University of California, San Francisco

San Francisco, California, 94158, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Harvard University Massachusetts General Hospital

Charlestown, Massachusetts, 02129, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Columbia University

New York, New York, 10032, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Case Western Reserve University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104-4283, United States

Location

University of Washington Harborview Medical Center

Seattle, Washington, 98104, United States

Location

University of British Columbia

Vancouver, British Columbia, V6T 2B5, Canada

Location

University of Toronto

Toronto, Ontario, M5T 2S8, Canada

Location

Related Publications (11)

• Boxer AL, Knopman DS, Kaufer DI, Grossman M, Onyike C, Graf-Radford N, Mendez M, Kerwin D, Lerner A, Wu CK, Koestler M, Shapira J, Sullivan K, Klepac K, Lipowski K, Ullah J, Fields S, Kramer JH, Merrilees J, Neuhaus J, Mesulam MM, Miller BL. Memantine in patients with frontotemporal lobar degeneration: a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2013 Feb;12(2):149-56. doi: 10.1016/S1474-4422(12)70320-4. Epub 2013 Jan 2.

  PMID: 23290598 BACKGROUND

• Boxer AL, Garbutt S, Seeley WW, Jafari A, Heuer HW, Mirsky J, Hellmuth J, Trojanowski JQ, Huang E, DeArmond S, Neuhaus J, Miller BL. Saccade abnormalities in autopsy-confirmed frontotemporal lobar degeneration and Alzheimer disease. Arch Neurol. 2012 Apr;69(4):509-17. doi: 10.1001/archneurol.2011.1021.

  PMID: 22491196 BACKGROUND

• Boxer AL, Lang AE, Grossman M, Knopman DS, Miller BL, Schneider LS, Doody RS, Lees A, Golbe LI, Williams DR, Corvol JC, Ludolph A, Burn D, Lorenzl S, Litvan I, Roberson ED, Hoglinger GU, Koestler M, Jack CR Jr, Van Deerlin V, Randolph C, Lobach IV, Heuer HW, Gozes I, Parker L, Whitaker S, Hirman J, Stewart AJ, Gold M, Morimoto BH; AL-108-231 Investigators. Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2/3 trial. Lancet Neurol. 2014 Jul;13(7):676-85. doi: 10.1016/S1474-4422(14)70088-2. Epub 2014 May 27.

  PMID: 24873720 BACKGROUND

• Rosen HJ, Alcantar O, Zakrzewski J, Shimamura AP, Neuhaus J, Miller BL. Metacognition in the behavioral variant of frontotemporal dementia and Alzheimer's disease. Neuropsychology. 2014 May;28(3):436-47. doi: 10.1037/neu0000012. Epub 2014 Feb 17.

  PMID: 24548124 BACKGROUND

• Rosen HJ, Alcantar O, Rothlind J, Sturm V, Kramer JH, Weiner M, Miller BL. Neuroanatomical correlates of cognitive self-appraisal in neurodegenerative disease. Neuroimage. 2010 Feb 15;49(4):3358-64. doi: 10.1016/j.neuroimage.2009.11.041. Epub 2009 Dec 1.

  PMID: 19961939 BACKGROUND

• Rohrer JD, Rosen HJ. Neuroimaging in frontotemporal dementia. Int Rev Psychiatry. 2013 Apr;25(2):221-9. doi: 10.3109/09540261.2013.778822.

  PMID: 23611351 BACKGROUND

• Boeve BF. Progressive supranuclear palsy. Parkinsonism Relat Disord. 2012 Jan;18 Suppl 1:S192-4. doi: 10.1016/S1353-8020(11)70060-8.

  PMID: 22166432 BACKGROUND

• Boeve BF. The multiple phenotypes of corticobasal syndrome and corticobasal degeneration: implications for further study. J Mol Neurosci. 2011 Nov;45(3):350-3. doi: 10.1007/s12031-011-9624-1. Epub 2011 Aug 19.

  PMID: 21853287 BACKGROUND

• 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.

  PMID: 35790423 DERIVED

• Gendron TF, Heckman MG, White LJ, Veire AM, Pedraza O, Burch AR, Bozoki AC, Dickerson BC, Domoto-Reilly K, Foroud T, Forsberg LK, Galasko DR, Ghoshal N, Graff-Radford NR, Grossman M, Heuer HW, Huey ED, Hsiung GR, Irwin DJ, Kaufer DI, Leger GC, Litvan I, Masdeu JC, Mendez MF, Onyike CU, Pascual B, Ritter A, Roberson ED, Rojas JC, Tartaglia MC, Wszolek ZK, Rosen H, Boeve BF, Boxer AL; ALLFTD consortium; Petrucelli L. Comprehensive cross-sectional and longitudinal analyses of plasma neurofilament light across FTD spectrum disorders. Cell Rep Med. 2022 Apr 19;3(4):100607. doi: 10.1016/j.xcrm.2022.100607. eCollection 2022 Apr 19.

  PMID: 35492244 DERIVED

• Rojas JC, Wang P, Staffaroni AM, Heller C, Cobigo Y, Wolf A, Goh SM, Ljubenkov PA, Heuer HW, Fong JC, Taylor JB, Veras E, Song L, Jeromin A, Hanlon D, Yu L, Khinikar A, Sivasankaran R, Kieloch A, Valentin MA, Karydas AM, Mitic LL, Pearlman R, Kornak J, Kramer JH, Miller BL, Kantarci K, Knopman DS, Graff-Radford N, Petrucelli L, Rademakers R, Irwin DJ, Grossman M, Ramos EM, Coppola G, Mendez MF, Bordelon Y, Dickerson BC, Ghoshal N, Huey ED, Mackenzie IR, Appleby BS, Domoto-Reilly K, Hsiung GR, Toga AW, Weintraub S, Kaufer DI, Kerwin D, Litvan I, Onyike CU, Pantelyat A, Roberson ED, Tartaglia MC, Foroud T, Chen W, Czerkowicz J, Graham DL, van Swieten JC, Borroni B, Sanchez-Valle R, Moreno F, Laforce R, Graff C, Synofzik M, Galimberti D, Rowe JB, Masellis M, Finger E, Vandenberghe R, de Mendonca A, Tagliavini F, Santana I, Ducharme S, Butler CR, Gerhard A, Levin J, Danek A, Otto M, Sorbi S, Cash DM, Convery RS, Bocchetta M, Foiani M, Greaves CV, Peakman G, Russell L, Swift I, Todd E, Rohrer JD, Boeve BF, Rosen HJ, Boxer AL; ALLFTD and GENFI consortia. Plasma Neurofilament Light for Prediction of Disease Progression in Familial Frontotemporal Lobar Degeneration. Neurology. 2021 May 4;96(18):e2296-e2312. doi: 10.1212/WNL.0000000000011848. Epub 2021 Apr 7.

  PMID: 33827960 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Plasma, serum, cell lines and cerebrospinal fluid will be retained by study investigators and stored at NIH-funded repositories.

MeSH Terms

Conditions

Frontotemporal Lobar Degeneration; Supranuclear Palsy, Progressive; Frontotemporal Dementia; Corticobasal Degeneration; Primary Progressive Nonfluent Aphasia; Amyotrophic Lateral Sclerosis; Color Vision Defects

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; TDP-43 Proteinopathies; Neurodegenerative Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Neurocognitive Disorders; Mental Disorders; Basal Ganglia Diseases; Movement Disorders; Ophthalmoplegia; Ocular Motility Disorders; Cranial Nerve Diseases; Tauopathies; Paralysis; Neurologic Manifestations; Eye Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Aphasia, Primary Progressive; Aphasia; Speech Disorders; Language Disorders; Communication Disorders; Neurobehavioral Manifestations; Spinal Cord Diseases; Motor Neuron Disease; Neuromuscular Diseases; Vision Disorders; Sensation Disorders; Cone Dystrophy; Eye Diseases, Hereditary

Study Officials

• Adam L Boxer, MD, PhD

  Study PI

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2015
• First Posted: February 19, 2015
• Study Start: September 1, 2014
• Primary Completion: August 1, 2020
• Study Completion: September 1, 2020
• Last Updated: May 21, 2021

Record last verified: 2021-05

Locations

US (15); CA (2)