4-Repeat Tauopathy Neuroimaging Initiative - Cycle 2

Progressive Supranuclear Palsy (PSP) Clinical Trial

— 4RTNI-2  

Official title:

The Four-Repeat Tauopathy Neuroimaging Initiative

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02966145
• Other study ID #: 4RTNI-2
• Secondary ID: 2R01AG038791-06A
• Status: Active, not recruiting
• Start date: January 2016
• Est. completion date: December 2024

Study information

• Verified date: January 2024
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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'.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 232
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Aphasia
• Aphasia, Primary Progressive
• Cortical-basal Ganglionic Degeneration (CBGD)
• Corticobasal Degeneration
• Corticobasal Degeneration (CBD)
• Corticobasal Syndrome (CBS)
• Frontotemporal Dementia
• Nonfluent Variant Primary Progressive Aphasia (nfvPPA)
• Oligosymptomatic/Variant Progressive Supranuclear Palsy (o/vPSP)
• Paralysis
• Pick Disease of the Brain
• Progressive Supranuclear Palsy (PSP)
• Supranuclear Palsy, Progressive
• Tauopathies

Intervention

Other:
• Observational Study

Locations

Country	Name	City	State
Canada	University of Toronto	Toronto	Ontario
United States	Johns Hopkins University	Baltimore	Maryland
United States	Harvard University - Massachusetts General Hospital	Charlestown	Massachusetts
United States	Columbia University	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Mayo Clinic - Rochester	Rochester	Minnesota
United States	University of California, San Diego (UCSD)	San Diego	California
United States	University of California, San Francisco (UCSF)	San Francisco	California

Sponsors (3)

Lead Sponsor	Collaborator
University of California, San Francisco	National Institute on Aging (NIA), National Institutes of Health (NIH)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (10)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

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