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Brain Network Activation and Gait and Posture in FXTAS (FXTAS-BNA)

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ClinicalTrials.gov Identifier: NCT02936531
Recruitment Status : Recruiting
First Posted : October 18, 2016
Last Update Posted : August 8, 2017
Sponsor:
Collaborator:
ElMindA Ltd
Information provided by (Responsible Party):
Dr. Sharon Hassin, Sheba Medical Center

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.

Condition or disease
Fragile X Associated Tremor-ataxia Syndrome FXTAS

Detailed Description:

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


Study Type : Observational
Estimated Enrollment : 150 participants
Observational Model: Case-Only
Time Perspective: Cross-Sectional
Official Title: Mapping Functional Networks of Brain Activity (Brain Network Activation) Based on Analysis of Evoked Response Potential (ERP) Signals and Registration of Posture and Gait-related Data in FMR1 Premutation Carriers and Patients With FXTAS.
Actual Study Start Date : November 1, 2016
Estimated Primary Completion Date : October 2018
Estimated Study Completion Date : November 2020


Group/Cohort
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



Primary Outcome Measures :
  1. BNA SCORE [ Time Frame: 1 day ]

Secondary Outcome Measures :
  1. FXTAS SCORE [ Time Frame: 1 day ]
    Clinical rating scale

  2. Posture and gait data [ Time Frame: 1 day ]
    Posture and gait data from Instrumental" timed up and go" test and items from the FXTAS rating scale.

  3. NeuroTrax™ Computerized Cognitive Tests [ Time Frame: 1 day ]
    Neuropsychological test

  4. MoCA score [ Time Frame: 1 day ]
    Neuropsychological test



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Ages Eligible for Study:   50 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Criteria

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

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): NCT02936531


Contacts
Contact: Sharon Hassin, MD 972547912020 shassin@post.tau.ac.il
Contact: Tsvia Fay-Karmon, MD tsviakar@gmail.com

Locations
Israel
Movement Disorders Institute, Sheba Medical center Recruiting
Ramat Gan, Israel, 5265601
Contact: Ayelet Brill, Ms.    +972-3-5304931    Ayelet.Brill@sheba.health.gov.il   
Sub-Investigator: Tsvia Fay-Karmon, Dr.         
Principal Investigator: Sharon Hassin-Baer, Prof.         
Sponsors and Collaborators
Sheba Medical Center
ElMindA Ltd
Investigators
Principal Investigator: Sharon Hassin, MD Movement Disorders Instuitute, Sheba Medical Center

Publications:

Responsible Party: Dr. Sharon Hassin, Director, Movement Disorders Institute, Sheba Medical Center
ClinicalTrials.gov Identifier: NCT02936531     History of Changes
Other Study ID Numbers: SHEBA-16-3940-SH-CTIL
First Posted: October 18, 2016    Key Record Dates
Last Update Posted: August 8, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Keywords provided by Dr. Sharon Hassin, Sheba Medical Center:
evoked response potential
ERP
Brain Network Activation
BNA
Biomarker

Additional relevant MeSH terms:
Ataxia
Fragile X Syndrome
Tremor
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Mental Retardation, X-Linked
Intellectual Disability
Neurobehavioral Manifestations
Sex Chromosome Disorders
Chromosome Disorders
Congenital Abnormalities
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Heredodegenerative Disorders, Nervous System