An observational study in Fragile X Associated Tremor-ataxia Syndrome and FXTAS, sponsored by Sheba Medical Center. Status unknown at 1 site in Israel. Open to participants aged 50 Years to 80 Years. Per ClinicalTrials.gov, last updated 2021-03-17.
Sponsored by Sheba Medical Center · Observational
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.
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
295 studies on the registry are indexed under Ataxia; 51 are open to participants now.
This study's planned enrollment of 150 is above the median of 100 across 70 observational studies indexed under Ataxia.
Browse Ataxia studies →Sheba Medical Center is the lead sponsor of 660 studies on the registry; 63 are open to participants now.
Counted across the registry records on this site, refreshed daily.
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.
Exclusion Criteria:
Patients positive for FMR1 premutation and meet diagnostic criteria for FXTAS
Patients positive for FMR1 premutation and do not meet diagnostic criteria for FXTAS
BNA SCORE
Time frame: 1 day
FXTAS SCORE
Clinical rating scale
Time frame: 1 day
Posture and gait data
Posture and gait data from Instrumental" timed up and go" test and items from the FXTAS rating scale.
Time frame: 1 day
NeuroTrax™ Computerized Cognitive Tests
Neuropsychological test
Time frame: 1 day
MoCA score
Neuropsychological test
Time frame: 1 day
Plan to share: Yes
This study is status unknown, as verified in Mar 2021. You cannot join it, but the record below documents what was studied.
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Sheba Medical Center