Clinical trial NCT04758624: Elucidating the Temporality of Structural and Functional Connectivity Changes in Essential Tremor After Successful Deep Brain Stimulation to the Dentato-rubro-thalamic Tract
Official title: Elucidating the Temporality of Structural and Functional Connectivity Changes in Essential Tremor After Successful Deep Brain Stimulation to the Dentato-rubro-thalamic Tract
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Essential Tremor
Keywords: deep brain stimulation
Lead sponsor: Northwell Health
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
First posted: 2021-02-17
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to elucidate the structural connectivity of the dentato-rubro-thalamic tract (DRTt) and to detect functional network changes due to DRTt stimulation


Eligibility criteria: Inclusion Criteria:

* the diagnosis of Essential Tremor, made by a movement disorder neurologist, where tremor is not secondary to any disease process or traumatic insult
* distal appendicular tremor, with minimal proximal component
* tremor refractory to multiple medication regimens and/or where the medications cause intolerable side effects
* tremor judged to be severely impacting their quality of life.

Exclusion Criteria:

* significant neurological disorder
* significant dementia or neurocognitive limitations as assessed by neuropsychiatry (when necessary)
* severe psychiatric illness with suicidal ideations
* previous surgery to destroy the target region of the brain
* surgical contraindications to DBS
* current major medical problems that affect brain anatomy,neurochemistry, or function, e.g., liver insufficiency, kidney insufficiency, cardiovascular problems, systemic infections, cancer, hypothyroidism, auto-immune diseases, and any current of history of brain disorder (seizure disorder, stroke, dementia, meningitis, encephalitis, degenerative neurologic diseases and head injury with loss of consciousness for any period of time)
* family history of hereditary neurologic disorder, besides essential tremors ET
* floating metallic objects in the body
* pregnancy
* alcohol or substance abuse/dependence in the past 6 months.

Primary outcomes:
measure: Structural connectivity as indicated by fractional anisotropy (FA) as measured by diffusion tensor imaging (DTI) MRI
timeFrame: Baseline before DBS implant
measure: Structural connectivity as indicated by fractional anisotropy (FA) as measured by diffusion tensor imaging (DTI) MRI
timeFrame: 24 months after start of DBS
measure: Structural connectivity as indicated by mean diffusivity as measured by diffusion tensor imaging (DTI) MRI
timeFrame: Baseline before DBS implant
measure: Structural connectivity as indicated by mean diffusivity as measured by diffusion tensor imaging (DTI) MRI
timeFrame: 24 months after start of DBS
measure: Structural connectivity as indicated by radial diffusivity as measured by diffusion tensor imaging (DTI) MRI
timeFrame: Baseline before DBS implant
measure: Structural connectivity as indicated by radial diffusivity as measured by diffusion tensor imaging (DTI) MRI
timeFrame: 24 months after start of DBS
measure: Structural connectivity as indicated by axial diffusivity as measured by diffusion tensor imaging (DTI) MRI
timeFrame: Baseline before DBS implant
measure: Structural connectivity as indicated by axial diffusivity as measured by diffusion tensor imaging (DTI) MRI
timeFrame: 24 months after start of DBS
measure: Functional connectivity as indicated by blood oxygen level dependent (BOLD) signal as measured by resting state functional MRI (rsfMRI)
timeFrame: Baseline before DBS implant
measure: Functional connectivity as indicated by blood oxygen level dependent (BOLD) signal as measured by resting state functional MRI (rsfMRI)
timeFrame: 24 months after start of DBS
measure: Functional connectivity as indicated by blood oxygen level dependent (BOLD) signal as measured by resting state functional MRI (rsfMRI)
timeFrame: Baseline before DBS is turned off
measure: Functional connectivity as indicated by blood oxygen level dependent (BOLD) signal as measured by resting state functional MRI (rsfMRI)
timeFrame: 72 hours after DBS is turned off
measure: Tremor as assessed by score on The Essential Tremor Rating Scale (TETRAS)
timeFrame: Baseline before DBS implant
measure: Tremor as assessed by score on The Essential Tremor Rating Scale (TETRAS)
timeFrame: 24 months after start of DBS
measure: Tremor as assessed by score on The Essential Tremor Rating Scale (TETRAS)
timeFrame: Baseline before DBS is turned off
measure: Tremor as assessed by score on The Essential Tremor Rating Scale (TETRAS)
timeFrame: 72 hours after DBS is turned off
measure: Tremor as assessed by score on The Essential Tremor Rating Scale (TETRAS)
timeFrame: During DBS placement surgery before active DBS
measure: Tremor as assessed by score on The Essential Tremor Rating Scale (TETRAS)
timeFrame: During DBS placement surgery during active DBS
measure: Spectral power recorded during intraoperative electrocorticography (ECoG)
timeFrame: During DBS placement surgery before active DBS
measure: Spectral power recorded during intraoperative electrocorticography (ECoG)
timeFrame: During DBS placement surgery during active DBS
Secondary outcomes:
measure: Ataxia as assessed by score on the Scale for the Assessment and Rating of Ataxia (SARA)
timeFrame: Baseline before DBS implant
measure: Ataxia as assessed by score on the Scale for the Assessment and Rating of Ataxia (SARA)
timeFrame: 24 months after start of DBS
measure: Ataxia as assessed by score on the Scale for the Assessment and Rating of Ataxia (SARA)
timeFrame: Baseline before DBS is turned off
measure: Ataxia as assessed by score on the Scale for the Assessment and Rating of Ataxia (SARA)
timeFrame: 72 hours after DBS is turned off
measure: Tremor amplitude as assessed by accelerometric power
timeFrame: Baseline before DBS is turned off
measure: Tremor amplitude as assessed by accelerometric power
timeFrame: 72 hours after DBS is turned off
Other outcomes:
Locations:
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
Study officials:
affiliation: Northwell Health
name: Albert J Fenoy, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Conner CR, Forseth KJ, Lozano AM, Ritter R 3rd, Fenoy AJ. Thalamo-cortical evoked potentials during stimulation of the dentato-rubro-thalamic tract demonstrate synaptic filtering. Neurotherapeutics. 2024 Jan;21(1):e00295. doi: 10.1016/j.neurot.2023.10.005. Epub 2023 Dec 19.