Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL)

NCT ID: NCT02365922

Last Updated: 2021-05-21

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 1489 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-09-30
• Study Completion Date: 2020-09-30

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.

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)

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Patients with FTLD or family members

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

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Center for Advancing Translational Sciences (NCATS)

NIH

Sponsor Role: collaborator

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

The Bluefield Project to Cure Frontotemporal Dementia

OTHER

Sponsor Role: collaborator

Tau Consortium

OTHER

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Adam L Boxer, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Study PI

Locations

University of Alabama

Birmingham, Alabama, United States

University of California, Los Angeles

Los Angeles, California, United States

University of California, San Diego

San Diego, California, United States

University of California, San Francisco

San Francisco, California, United States

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States

Northwestern University

Chicago, Illinois, United States

Johns Hopkins University

Baltimore, Maryland, United States

Harvard University Massachusetts General Hospital

Charlestown, Massachusetts, United States

Mayo Clinic - Rochester

Rochester, Minnesota, United States

Washington University

St Louis, Missouri, United States

Columbia University

New York, New York, United States

University of North Carolina

Chapel Hill, North Carolina, United States

Case Western Reserve University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

University of Washington Harborview Medical Center

Seattle, Washington, United States

University of British Columbia

Vancouver, British Columbia, Canada

University of Toronto

Toronto, Ontario, Canada

Countries

United States; Canada

References

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.

Reference Type: BACKGROUND

PMID: 23290598 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22491196 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24873720 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24548124 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19961939 (View on PubMed)

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

Reference Type: BACKGROUND

PMID: 23611351 (View on PubMed)

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

Reference Type: BACKGROUND

PMID: 22166432 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21853287 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35790423 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35492244 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33827960 (View on PubMed)

Other Identifiers

1U54NS092089-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ARTFL8101

Identifier Type: -

Identifier Source: org_study_id