Brain Network Activation and Gait and Posture in FXTAS

NCT ID: NCT02936531

Last Updated: 2021-03-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Total Enrollment

150 participants

Study Classification

OBSERVATIONAL

Study Start Date

2016-11-01

Study Completion Date

2022-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a progressive, late-onset (\>50 years) multisystem neurodegenerative disorder, associated with an expansion in the 5ʹuntranslated region of the fragile X mental retardation 1 (FMR1) gene that consists of 55-200 CGG repeats, termed the FMR1 gene premutation. While the prevalence of the premutation is 1 in 150-300 females, and 1 in 400-850 males, the penetrance of FXTAS in male carriers is \~40% compared to less than 20% in females.

The mean age of onset of FXTAS is 60 years, presenting with intention tremor, cerebellar ataxia, neuropathic pain, memory and/or executive function deficits, parkinsonism, and psychiatric manifestations such as depression, anxiety and/or apathy.

There are typical MRI findings in FXTAS patients, including increased T2-weighted signal intensity in the middle cerebellar peduncles, cerebellar and cerebral atrophy and volume loss of the corpus callosum.

Currently, no definitive diagnostic tests exist for the symptomatic condition, FXTAS, in FMR1 premutation carriers, making it difficult to diagnose, particularly in the early stages of disease pathology. ElMindA, an Israeli company established in 2006, that focuses on the mapping of neuro-electrophysiological activity, has developed a novel method of mapping functional networks of brain activity (Brain Network Activation or BNA) based on analysis of evoked response potential (ERP) signals. Patients whose underlying disease involves impairment in brain circuitry and connectivity are expected to produce abnormal activity templates in response to the same paradigm, both as a result of failing to adhere to the normal pattern and of recruiting compensatory pathways and strategies to tackle the task. The essence of BNA analysis is the extraction of brain activity patterns common to a group of normal subjects, against which the brain activity of individual subjects may be compared. Patients with FXTAS have been found to exhibit executive and memory deficits along with altered prefrontal cortex activity in functional MRI studies and the investigators suspect that patients with FXTAS and also FMR1 premutation carriers in the early phase of neurodegeneration (even before exhibiting overt clinical symptoms of FXTAS) may display abnormal BNA patterns. Accordingly, at Sheba medical center the investigators have computed individual BNA scores for 30 healthy control subjects and thus defined the BNA patterns of healthy subjects to be used for comparison wit study subjects.

The goal of the study is to identify and characterize a potential neurophysiological biomarker for early stage FXTAS and for disease progression by evaluating the electrophysiological activity in both asymptomatic FMR1 Premutation carriers and in patients with various stages (duration) of FXTAS. Additionally correlations will be studied between these BNA data and demographics (gender, age and disease duration). length of the pathological CGG repeat expansion as well as FXTAS score, gait and posture abnormalities (obtained by instrumental timed up and go evaluation) and neuropsychological status.

Characterization of neuro-electrophysiological biomarkers may be important to detect early transformation from asymptomatic carriership to neurodegeneration and FXTAS and to enable early interventions and monitoring of response to treatment

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Fragile X Associated Tremor-ataxia Syndrome FXTAS

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

CASE_ONLY

Study Time Perspective

CROSS_SECTIONAL

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

FXTAS

Patients positive for FMR1 premutation and meet diagnostic criteria for FXTAS

No interventions assigned to this group

FMR1 premutation asymptomatic

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

No interventions assigned to this group

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

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

Exclusion Criteria

* Severe disability unable to perform tests
* treatment with neuroleptics
* other brain disease or pathology
* deafness or blindness
Minimum Eligible Age

50 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

ElMindA Ltd

INDUSTRY

Sponsor Role collaborator

Sheba Medical Center

OTHER_GOV

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Dr. Sharon Hassin

Director, Movement Disorders Institute

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Sharon Hassin, MD

Role: PRINCIPAL_INVESTIGATOR

Movement Disorders Instuitute, Sheba Medical Center

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Movement Disorders Institute, Sheba Medical center

Ramat Gan, , Israel

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Israel

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Sharon Hassin, MD

Role: CONTACT

972547912020

Tsvia Fay-Karmon, MD

Role: CONTACT

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Ayelet Brill, Ms.

Role: primary

+972-3-5304931

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 18057320 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11445641 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15052536 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12638084 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15000674 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12791039 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18565783 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12427636 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17266074 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25116862 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25006969 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25763861 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11690607 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21616709 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

SHEBA-3490-16-SMC

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Mirroring a Movement
NCT00123448 COMPLETED