4-Repeat Tauopathy Neuroimaging Initiative - Cycle 2 (4RTNI-2)

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ClinicalTrials.gov Identifier: NCT02966145

Recruitment Status : Recruiting

First Posted : November 17, 2016

Last Update Posted : September 17, 2018

See Contacts and Locations

Sponsor:

Collaborators:

National Institutes of Health (NIH)

National Institute on Aging (NIA)

Information provided by (Responsible Party):

University of California, San Francisco

Study Description

Brief Summary:

The goal of this study is to identify the most reliable methods of analysis for tracking CBD, PSP, and o/vPSP over time. The results from this study may be used in the future to calculate statistical power for clinical drug trials. The study will also provide information about the relative value of novel imaging techniques for diagnosis, as well as the value of imaging techniques versus testing of blood, urine, and cerebrospinal fluid (CSF) 'biomarkers'.

Condition or disease	Intervention/treatment
Corticobasal Degeneration (CBD) Corticobasal Syndrome (CBS) Cortical-basal Ganglionic Degeneration (CBGD) Progressive Supranuclear Palsy (PSP) Nonfluent Variant Primary Progressive Aphasia (nfvPPA) Oligosymptomatic/Variant Progressive Supranuclear Palsy (o/vPSP)	Other: Observational Study

Study Design

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Study Type :	Observational
Estimated Enrollment :	232 participants
Observational Model:	Cohort
Time Perspective:	Prospective
Official Title:	The Four-Repeat Tauopathy Neuroimaging Initiative
Study Start Date :	January 2016
Estimated Primary Completion Date :	December 2021
Estimated Study Completion Date :	December 2021

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: CHMP2B-related frontotemporal dementia GRN-related frontotemporal dementia Frontotemporal dementia with parkinsonism-17 Progressive supranuclear palsy

Genetic and Rare Diseases Information Center resources: Pick's Disease Frontotemporal Dementia Frontotemporal Dementia, Ubiquitin-positive Primary Progressive Aphasia Semantic Dementia Progressive Supranuclear Palsy Corticobasal Degeneration Ocular Motility Disorders Motor Neuro-ophthalmic Disorders

U.S. FDA Resources

Groups and Cohorts

Group/Cohort	Intervention/treatment
PSP & CBD Observational study of participants with a diagnosis of Progressive Supranuclear Palsy or Corticobasal Degeneration (also called Corticobasal Syndrome or Cortical-basal Ganglionic Degeneration).	Other: Observational Study
o/vPSP Observational study of participants with a diagnosis of an oligosymptomatic or variant Progressive Supranuclear Palsy syndrome.	Other: Observational Study
Normal Volunteers Observational study of participants with no known diagnosis of a neurological or neurodegenerative condition, and no known history of memory complaints.	Other: Observational Study

Outcome Measures

Primary Outcome Measures :

Tau-PET Brain Scan [ Time Frame: Baseline, 1-year, and 2-years. ]
Change from Baseline of Tau protein distribution in the brain.
Amyloid-PET Brain Scan [ Time Frame: Baseline ]
Presence of Amyloid in the brain at Baseline.
Brain Volume on MRI [ Time Frame: Baseline, 6-months, 1-year, and 2-years. ]
Change from Baseline of brain tissue volume.
Progressive Supranuclear Palsy Rating Scale (PSPRS) [ Time Frame: Baseline, 6-months, 1-year, and 2-years. ]
Change from Baseline of this rating scale.
Corticobasal Degeneration Functional Scale (CBDFS) [ Time Frame: Baseline, 6-months, 1-year, and 2-years. ]
Change from Baseline of this rating scale.
Eye Movement Function [ Time Frame: Baseline, 6-months, 1-year, and 2-years. ]
Change from Baseline of eye movement function.
Retinal Imaging [ Time Frame: Baseline, 6-months, 1-year, and 2-years. ]
Change from Baseline of retinal thickness.
UDS Neuropsychological Testing Battery, including supplemental FTLD Module [ Time Frame: Baseline, 6-months, 1-year, and 2-years. ]
Change fromm Baseline of cognitive function.

Biospecimen Retention: Samples With DNA

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

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	40 Years to 80 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes
Sampling Method:	Probability Sample

Study Population

Participants diagnosed with Corticobasal Syndrome (CBS), Corticobasal Degeneration (CBD), Progressive Supranuclear Palsy, or Oligo- or Variant- Progressive Supranuclear Palsy (o/vPSP); Healthy Volunteers.

Criteria

Inclusion Criteria:

No known history of neurological disease, or meet criteria for one of the following: Corticobasal Syndrome or Degeneration (CBS or CBD); Progressive Supranuclear Palsy (PSP); or Oligo- or Variant- Progressive Supranuclear Palsy (o/vPSP)
Needs a reliable study partner who has frequent contact with the participant, who is available to provide information about the participant, and who can accompany the participant to research visits as needed
Must be willing and able to undergo testing procedures, which include longitudinal follow-up visits
Must be able to walk five steps with minimal assistance

Exclusion Criteria:

Significant neurological disease other than CBD, PSP, or a variant PSP syndrome.
Presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, or metal fragments or metal objects in the eyes, skin, or body
In the site investigator's opinion, inability to complete sufficient key study procedures, or some other equivalent assessment of impairment

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02966145

Contacts

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Contact: Eliya Ben-Asher, BS	(415) 476-2941	Eliya.Ben-Asher@ucsf.edu
Contact: Hilary Heuer, PhD	(415) 476-6743	Hilary.Heuer@ucsf.edu

Locations

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United States, California
University of California, San Diego (UCSD)	Recruiting
San Diego, California, United States, 92037
Contact: Ileana Rubio 858-822-5751 irubio@ucsd.edu
Principal Investigator: Irene Litvan, MD
University of California, San Francisco (UCSF)	Recruiting
San Francisco, California, United States, 94158
Contact: Eliya Ben-Asher, BS 415-476-2941 Eliya.Ben-Asher@ucsf.edu
United States, Massachusetts
Harvard University - Massachusetts General Hospital	Recruiting
Charlestown, Massachusetts, United States, 02129
Contact: Samantha Krivensky, BA 617-726-6205 SKrivensky@mgh.harvard.edu
Principal Investigator: Bradford C Dickerson, MD
United States, Minnesota
Mayo Clinic - Rochester	Recruiting
Rochester, Minnesota, United States, 55905
Contact: Ruth Kraft 507-538-9487 Kraft.Ruth@mayo.edu
Principal Investigator: Bradley F Boeve, MD
United States, Pennsylvania
University of Pennsylvania	Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Courtney Igne 215-662-3596 cigne@mail.med.upenn.edu
Principal Investigator: Murray Grossman, MD
Canada, Ontario
University of Toronto	Recruiting
Toronto, Ontario, Canada, M5T 2S8
Contact: Cristina Salvo Cristina.Salvo@uhn.ca
Principal Investigator: Maria Carmela Tartaglia, MD, FRCPC

Sponsors and Collaborators

University of California, San Francisco

National Institutes of Health (NIH)

National Institute on Aging (NIA)

Investigators

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Principal Investigator:	Adam L Boxer, MD, PhD	University of California, San Francisco

More Information

Publications:

Armstrong MJ, Litvan I, Lang AE, Bak TH, Bhatia KP, Borroni B, Boxer AL, Dickson DW, Grossman M, Hallett M, Josephs KA, Kertesz A, Lee SE, Miller BL, Reich SG, Riley DE, Tolosa E, Tröster AI, Vidailhet M, Weiner WJ. Criteria for the diagnosis of corticobasal degeneration. Neurology. 2013 Jan 29;80(5):496-503. doi: 10.1212/WNL.0b013e31827f0fd1.

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, Höglinger 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.

Fagan AM, Shaw LM, Xiong C, Vanderstichele H, Mintun MA, Trojanowski JQ, Coart E, Morris JC, Holtzman DM. Comparison of analytical platforms for cerebrospinal fluid measures of β-amyloid 1-42, total tau, and p-tau181 for identifying Alzheimer disease amyloid plaque pathology. Arch Neurol. 2011 Sep;68(9):1137-44. doi: 10.1001/archneurol.2011.105. Epub 2011 May 9.

Golbe LI, Ohman-Strickland PA. A clinical rating scale for progressive supranuclear palsy. Brain. 2007 Jun;130(Pt 6):1552-65. Epub 2007 Apr 2.

Heuer HW, Mirsky JB, Kong EL, Dickerson BC, Miller BL, Kramer JH, Boxer AL. Antisaccade task reflects cortical involvement in mild cognitive impairment. Neurology. 2013 Oct 1;81(14):1235-43. doi: 10.1212/WNL.0b013e3182a6cbfe. Epub 2013 Aug 28.

Litvan I, Agid Y, Calne D, Campbell G, Dubois B, Duvoisin RC, Goetz CG, Golbe LI, Grafman J, Growdon JH, Hallett M, Jankovic J, Quinn NP, Tolosa E, Zee DS. Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology. 1996 Jul;47(1):1-9. Review.

Scherling CS, Hall T, Berisha F, Klepac K, Karydas A, Coppola G, Kramer JH, Rabinovici G, Ahlijanian M, Miller BL, Seeley W, Grinberg LT, Rosen H, Meredith J Jr, Boxer AL. Cerebrospinal fluid neurofilament concentration reflects disease severity in frontotemporal degeneration. Ann Neurol. 2014 Jan;75(1):116-26. doi: 10.1002/ana.24052. Epub 2014 Jan 2.

Stamelou M, de Silva R, Arias-Carrión O, Boura E, Höllerhage M, Oertel WH, Müller U, Höglinger GU. Rational therapeutic approaches to progressive supranuclear palsy. Brain. 2010 Jun;133(Pt 6):1578-90. doi: 10.1093/brain/awq115. Epub 2010 May 14. Review.

Steele JC, Richardson JC, Olszewski J. Progressive supranuclear palsy: a heterogeneous degeneration involving the brain stem, Basal Ganglia and cerebellum with vertical gaze and pseudobulbar palsy, nuchal dystonia and dementia. Semin Neurol. 2014 Apr;34(2):129-50. doi: 10.1055/s-0034-1377058. Epub 2014 Jun 25.

Wagshal D, Sankaranarayanan S, Guss V, Hall T, Berisha F, Lobach I, Karydas A, Voltarelli L, Scherling C, Heuer H, Tartaglia MC, Miller Z, Coppola G, Ahlijanian M, Soares H, Kramer JH, Rabinovici GD, Rosen HJ, Miller BL, Meredith J, Boxer AL. Divergent CSF τ alterations in two common tauopathies: Alzheimer's disease and progressive supranuclear palsy. J Neurol Neurosurg Psychiatry. 2015 Mar;86(3):244-50. doi: 10.1136/jnnp-2014-308004. Epub 2014 Jun 4.

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Responsible Party:	University of California, San Francisco
ClinicalTrials.gov Identifier:	NCT02966145 History of Changes
Other Study ID Numbers:	4RTNI-2 2R01AG038791-06A1 ( U.S. NIH Grant/Contract )
First Posted:	November 17, 2016 Key Record Dates
Last Update Posted:	September 17, 2018
Last Verified:	September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Keywords provided by University of California, San Francisco:


CBD CBS CBGD PSP nfvPPA oPSP vPSP o/vPSP Corticobasal Degeneration Corticobasal Syndrome Cortocal-basal Ganglionic Degeneration	Progressive Supranuclear Palsy Nonfluent Variant Primary Progressive Aphasia Oligosymptomatic Progressive Supranuclear Palsy Variant Progressive Supranuclear Palsy Biomarker Neuroimaging MRI PET Tau Oculomotor Retinal Imaging

Additional relevant MeSH terms:

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Paralysis Aphasia Supranuclear Palsy, Progressive Tauopathies Aphasia, Primary Progressive Pick Disease of the Brain Frontotemporal Dementia Neurologic Manifestations Nervous System Diseases Signs and Symptoms Speech Disorders Language Disorders Communication Disorders Neurobehavioral Manifestations Basal Ganglia Diseases	Brain Diseases Central Nervous System Diseases Movement Disorders Ophthalmoplegia Ocular Motility Disorders Cranial Nerve Diseases Neurodegenerative Diseases Eye Diseases Dementia Neurocognitive Disorders Mental Disorders Frontotemporal Lobar Degeneration TDP-43 Proteinopathies Proteostasis Deficiencies Metabolic Diseases

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