Brain Network Activation and Gait and Posture in FXTAS

NCT02936531 | Unknown

• 1 other identifier: SHEBA-3490-16-SMC
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

In this study the investigators aim to identify and characterize a potential neurophysiological biomarker by mapping functional networks of brain activity (Brain Network Activation, BNA) based on analysis of evoked response potential (ERP) signals in both asymptomatic FMR1 premutation carriers and in patients with various stages of FXTAS. Additionally correlations will be studied between these BNA scores and demographics (gender, age and disease duration) as well as genetic mutation and clinical scores.

Conditions

Fragile X Associated Tremor-ataxia Syndrome; FXTAS

Keywords

evoked response potential; ERP; Brain Network Activation; BNA; Biomarker

Outcome Measures

Primary Outcomes (1)

• BNA SCORE

  1 day

Secondary Outcomes (4)

• FXTAS SCORE

  1 day

• Posture and gait data

  1 day

• NeuroTrax™ Computerized Cognitive Tests

  1 day

• MoCA score

  1 day

Study Arms (2)

FXTAS

Patients positive for FMR1 premutation and meet diagnostic criteria for FXTAS

FMR1 premutation asymptomatic

Patients positive for FMR1 premutation and do not meet diagnostic criteria for FXTAS

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Men and women above the age of 50, that are FMR1 premutation carriers (55-200 CGG repeats), both symptomatic (with possible or probable FXTAS) or neurologically asymptomatic.

You may qualify if:

• FMR1 premutation carriers (55-200 CGG repeats)
• symptomatic (with possible or probable FXTAS) or neurologically asymptomatic.

You may not qualify if:

• Severe disability unable to perform tests
• treatment with neuroleptics
• other brain disease or pathology
• deafness or blindness

Sponsors & Collaborators

• Sheba Medical Center: lead
• ElMindA Ltd: collaborator

Study Sites (1)

Movement Disorders Institute, Sheba Medical center

Ramat Gan, 5265601, Israel

RECRUITING

Related Publications (14)

• Leehey MA, Berry-Kravis E, Goetz CG, Zhang L, Hall DA, Li L, Rice CD, Lara R, Cogswell J, Reynolds A, Gane L, Jacquemont S, Tassone F, Grigsby J, Hagerman RJ, Hagerman PJ. FMR1 CGG repeat length predicts motor dysfunction in premutation carriers. Neurology. 2008 Apr 15;70(16 Pt 2):1397-402. doi: 10.1212/01.wnl.0000281692.98200.f5. Epub 2007 Dec 5.

  PMID: 18057320 BACKGROUND

• Hagerman RJ, Leehey M, Heinrichs W, Tassone F, Wilson R, Hills J, Grigsby J, Gage B, Hagerman PJ. Intention tremor, parkinsonism, and generalized brain atrophy in male carriers of fragile X. Neurology. 2001 Jul 10;57(1):127-30. doi: 10.1212/wnl.57.1.127.

  PMID: 11445641 BACKGROUND

• Hagerman PJ, Hagerman RJ. The fragile-X premutation: a maturing perspective. Am J Hum Genet. 2004 May;74(5):805-16. doi: 10.1086/386296. Epub 2004 Mar 29.

  PMID: 15052536 BACKGROUND

• Jacquemont S, Hagerman RJ, Leehey M, Grigsby J, Zhang L, Brunberg JA, Greco C, Des Portes V, Jardini T, Levine R, Berry-Kravis E, Brown WT, Schaeffer S, Kissel J, Tassone F, Hagerman PJ. Fragile X premutation tremor/ataxia syndrome: molecular, clinical, and neuroimaging correlates. Am J Hum Genet. 2003 Apr;72(4):869-78. doi: 10.1086/374321. Epub 2003 Mar 12.

  PMID: 12638084 BACKGROUND

• Jacquemont S, Farzin F, Hall D, Leehey M, Tassone F, Gane L, Zhang L, Grigsby J, Jardini T, Lewin F, Berry-Kravis E, Hagerman PJ, Hagerman RJ. Aging in individuals with the FMR1 mutation. Am J Ment Retard. 2004 Mar;109(2):154-64. doi: 10.1352/0895-8017(2004)1092.0.CO;2.

  PMID: 15000674 BACKGROUND

• Rogers C, Partington MW, Turner GM. Tremor, ataxia and dementia in older men may indicate a carrier of the fragile X syndrome. Clin Genet. 2003 Jul;64(1):54-6. doi: 10.1034/j.1399-0004.2003.00089.x.

  PMID: 12791039 BACKGROUND

• Hall DA, Howard K, Hagerman R, Leehey MA. Parkinsonism in FMR1 premutation carriers may be indistinguishable from Parkinson disease. Parkinsonism Relat Disord. 2009 Feb;15(2):156-9. doi: 10.1016/j.parkreldis.2008.04.037. Epub 2008 Jun 20.

  PMID: 18565783 BACKGROUND

• Brunberg JA, Jacquemont S, Hagerman RJ, Berry-Kravis EM, Grigsby J, Leehey MA, Tassone F, Brown WT, Greco CM, Hagerman PJ. Fragile X premutation carriers: characteristic MR imaging findings of adult male patients with progressive cerebellar and cognitive dysfunction. AJNR Am J Neuroradiol. 2002 Nov-Dec;23(10):1757-66.

  PMID: 12427636 BACKGROUND

• Grigsby J, Brega AG, Leehey MA, Goodrich GK, Jacquemont S, Loesch DZ, Cogswell JB, Epstein J, Wilson R, Jardini T, Gould E, Bennett RE, Hessl D, Cohen S, Cook K, Tassone F, Hagerman PJ, Hagerman RJ. Impairment of executive cognitive functioning in males with fragile X-associated tremor/ataxia syndrome. Mov Disord. 2007 Apr 15;22(5):645-50. doi: 10.1002/mds.21359.

  PMID: 17266074 BACKGROUND

• Ray S, Miller M, Karalunas S, Robertson C, Grayson DS, Cary RP, Hawkey E, Painter JG, Kriz D, Fombonne E, Nigg JT, Fair DA. Structural and functional connectivity of the human brain in autism spectrum disorders and attention-deficit/hyperactivity disorder: A rich club-organization study. Hum Brain Mapp. 2014 Dec;35(12):6032-48. doi: 10.1002/hbm.22603. Epub 2014 Aug 13.

  PMID: 25116862 BACKGROUND

• Karalunas SL, Fair D, Musser ED, Aykes K, Iyer SP, Nigg JT. Subtyping attention-deficit/hyperactivity disorder using temperament dimensions: toward biologically based nosologic criteria. JAMA Psychiatry. 2014 Sep;71(9):1015-24. doi: 10.1001/jamapsychiatry.2014.763.

  PMID: 25006969 BACKGROUND

• O'Keefe JA, Robertson-Dick E, Dunn EJ, Li Y, Deng Y, Fiutko AN, Berry-Kravis E, Hall DA. Characterization and Early Detection of Balance Deficits in Fragile X Premutation Carriers With and Without Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS). Cerebellum. 2015 Dec;14(6):650-62. doi: 10.1007/s12311-015-0659-7.

  PMID: 25763861 BACKGROUND

• Michel CM, Thut G, Morand S, Khateb A, Pegna AJ, Grave de Peralta R, Gonzalez S, Seeck M, Landis T. Electric source imaging of human brain functions. Brain Res Brain Res Rev. 2001 Oct;36(2-3):108-18. doi: 10.1016/s0165-0173(01)00086-8.

  PMID: 11690607 BACKGROUND

• Caviness JN, Adler CH, Hentz JG, Shill HA, Evidente VG, Driver-Dunckley ED, Sabbagh MN, Sue L, Beach TG. Incidental Lewy body disease: electrophysiological findings suggesting pre-clinical Lewy body disorders. Clin Neurophysiol. 2011 Dec;122(12):2426-32. doi: 10.1016/j.clinph.2011.03.033. Epub 2011 May 26.

  PMID: 21616709 BACKGROUND

MeSH Terms

Conditions

Fragile X Tremor Ataxia Syndrome

Study Officials

• Sharon Hassin, MD

  Movement Disorders Instuitute, Sheba Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sharon Hassin, MD

CONTACT

972547912020; shassin@post.tau.ac.il

Tsvia Fay-Karmon, MD

CONTACT

tsviakar@gmail.com

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Movement Disorders Institute

Study Record Dates

• First Submitted: October 15, 2016
• First Posted: October 18, 2016
• Study Start: November 1, 2016
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2022
• Last Updated: March 17, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will share

Locations

IL (1)