4-Repeat Tauopathy Neuroimaging Initiative - Cycle 2

NCT02966145 | Completed

• 2 other identifiers: 4RTNI-22R01AG038791-06A1
• Study Type: observational
• Target: 293
• Locations: 2 countries
• Sites: 8

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'.

Conditions

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)

Keywords

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

Outcome Measures

Primary Outcomes (8)

• Tau-PET Brain Scan

  Change from Baseline of Tau protein distribution in the brain.

  Baseline, 1-year, and 2-years.

• Amyloid-PET Brain Scan

  Presence of Amyloid in the brain at Baseline.

  Baseline

• Brain Volume on MRI

  Change from Baseline of brain tissue volume.

  Baseline, 6-months, 1-year, and 2-years.

• Progressive Supranuclear Palsy Rating Scale (PSPRS)

  Change from Baseline of this rating scale.

  Baseline, 6-months, 1-year, and 2-years.

• Corticobasal Degeneration Functional Scale (CBDFS)

  Change from Baseline of this rating scale.

  Baseline, 6-months, 1-year, and 2-years.

• Eye Movement Function

  Change from Baseline of eye movement function.

  Baseline, 6-months, 1-year, and 2-years.

• Retinal Imaging

  Change from Baseline of retinal thickness.

  Baseline, 6-months, 1-year, and 2-years.

• UDS Neuropsychological Testing Battery, including supplemental FTLD Module

  Change fromm Baseline of cognitive function.

  Baseline, 6-months, 1-year, and 2-years.

Study Arms (3)

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

Interventions

Observational Study OTHER

Normal Volunteers; PSP & CBD; o/vPSP

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Institutes of Health (NIH): collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (8)

University of California, San Diego (UCSD)

San Diego, California, 92037, United States

Location

University of California, San Francisco (UCSF)

San Francisco, California, 94158, 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

Columbia University

New York, New York, 10032, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Toronto

Toronto, Ontario, M5T 2S8, Canada

Location

Related Publications (13)

• 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, Troster 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.

  PMID: 23359374 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

• 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 beta-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.

  PMID: 21555603 BACKGROUND

• Golbe LI, Ohman-Strickland PA. A clinical rating scale for progressive supranuclear palsy. Brain. 2007 Jun;130(Pt 6):1552-65. doi: 10.1093/brain/awm032. Epub 2007 Apr 2.

  PMID: 17405767 BACKGROUND

• 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.

  PMID: 23986300 BACKGROUND

• 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. doi: 10.1212/wnl.47.1.1.

  PMID: 8710059 BACKGROUND

• 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.

  PMID: 24242746 BACKGROUND

• Stamelou M, de Silva R, Arias-Carrion O, Boura E, Hollerhage M, Oertel WH, Muller U, Hoglinger 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.

  PMID: 20472654 BACKGROUND

• 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. No abstract available.

  PMID: 24963673 BACKGROUND

• 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 tau 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.

  PMID: 24899730 BACKGROUND

• Scotton WJ, Shand C, Todd EG, Bocchetta M, Kobylecki C, Cash DM, VandeVrede L, Heuer HW, Quaegebeur A, Young AL, Oxtoby N, Alexander D, Rowe JB, Morris HR; PROSPECT Consortium; Boxer AL; 4RTNI Consortium; Rohrer JD, Wijeratne PA. Distinct spatiotemporal atrophy patterns in corticobasal syndrome are associated with different underlying pathologies. Brain Commun. 2025 Feb 11;7(2):fcaf066. doi: 10.1093/braincomms/fcaf066. eCollection 2025.

  PMID: 40070441 BACKGROUND

• Wise A, Li J, Yamakawa M, Loureiro J, Peterson B, Worringer K, Sivasankaran R, Palma JA, Mitic L, Heuer HW, Lario-Lago A, Staffaroni AM, Clark A, Taylor J, Ljubenkov PA, Vandevrede L, Grinberg LT, Spina S, Seeley WW, Miller BL, Boeve BF, Dickerson BC, Grossman M, Litvan I, Pantelyat A, Tartaglia MC, Zhang Z, Wills AA, Rexach J, Rojas JC, Boxer AL; as the 4-Repeat Tauopathy Neuroimaging Initiative. CSF Proteomics in Patients With Progressive Supranuclear Palsy. Neurology. 2024 Aug 13;103(3):e209585. doi: 10.1212/WNL.0000000000209585. Epub 2024 Jul 3.

  PMID: 38959435 RESULT

• Garcia-Cordero I, Anastassiadis C, Khoja A, Morales-Rivero A, Thapa S, Vasilevskaya A, Davenport C, Sumra V, Couto B, Multani N, Taghdiri F, Anor C, Misquitta K, Vandevrede L, Heuer H, Tang-Wai D, Dickerson B, Pantelyat A, Litvan I, Boeve B, Rojas JC, Ljubenkov P, Huey E, Fox S, Kovacs GG, Boxer A, Lang A, Tartaglia MC; 4-R-Tauopathy Neuroimaging Initiative Consortium, and the Alzheimer's Disease Neuroimaging Initiative. Evaluating the Effect of Alzheimer's Disease-Related Biomarker Change in Corticobasal Syndrome and Progressive Supranuclear Palsy. Ann Neurol. 2024 Jul;96(1):99-109. doi: 10.1002/ana.26930. Epub 2024 Apr 5.

  PMID: 38578117 RESULT

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.

MeSH Terms

Conditions

Corticobasal Degeneration; Supranuclear Palsy, Progressive; Pick Disease of the Brain

Interventions

Observation

Condition Hierarchy (Ancestors)

Tauopathies; Neurodegenerative Diseases; Nervous System Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Ophthalmoplegia; Ocular Motility Disorders; Cranial Nerve Diseases; Paralysis; Neurologic Manifestations; Eye Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Frontotemporal Dementia; Frontotemporal Lobar Degeneration; Dementia; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques

Study Officials

• Adam L Boxer, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 15, 2016
• First Posted: November 17, 2016
• Study Start: January 1, 2016
• Primary Completion: February 28, 2024
• Study Completion: February 28, 2024
• Last Updated: April 13, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share

Locations

CA (1); US (7)