Dual Lead Thalamic Deep Brain Recording (DBR)-DBS Interface for Closed Loop Control of Severe Essential Tremor

Study Overview
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Brief Summary
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This is a feasibility study based on physician-initiated Investigational Device Exemption (IDE) including intraoperative experiments and chronic testing of implanted dual thalamic DBS lead systems. This study will inform protocols for optimal use of implanted next-gen DBS systems for primarily tremor control in refractory essential tremor.If the approach appears to be successful, the pilot data generated will be used to base a future pivotal trial for FDA approval for enhanced tremor control and adaptive DBS (aDBS) functionality of DBS systems.

Detailed Description
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Ventralis intermedius nucleus of the thalamus (VIM) Deep Brain Stimulation (DBS) has emerged as a highly effective treatment for essential tremor, which is an incurable, degenerative brain disorder that results in progressively debilitating tremor, afflicting an estimated 7 million people in the US (2.2% of the population). Clinical observation shows, however, that disease progression results in eventual recurrence of debilitating tremor in 10 to 20% of VIM DBS patients. DBS revision surgery, with replacement of sub-optimally positioned VIM DBS leads and addition of an ipsilateral ventralis oralis (VO) DBS lead, has emerged as an effective rescue strategy for many such patients with delayed failure of VIM DBS therapy. Since essential tremors are typically not continuous, tremor suppressing DBS therapy need not necessarily be delivered continuously and could theoretically be effective if delivered only when movement intent or tremor is present. Our central hypothesis is that a VIM+VO DBS system capable of detecting the neurophysiologic markers of essential tremor (ET) associated with goal directed movements, and providing responsive dual lead thalamic stimulation in a targeted and personalized manner, would provide improved suppression of severe tremor, reduce adverse effects associated with continuous stimulation, and prolong the battery life of the implantable neurostimulator (INS), decreasing the frequency of surgical procedures necessary to replace devices with depleted batteries.

Official Title
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Dual Lead Thalamic DBR-DBS Interface for Closed Loop Control of Severe Essential Tremor

Conditions
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Essential Tremor

Intervention / Treatment
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* Device: Medtronic Summit Rechargable (RC)+S
* Procedure: ipsilateral thalamic (VIM+VO) DBS
* Procedure: standard ET DBS
* Procedure: ipsilateral VO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient gives an informed consent. Patient is over 21 years of age. Patient is diagnosed with a postural-intention (essential) tremor for at least 3 years, meets diagnostic criteria for ET, has been evaluated and examined by a movement disorders fellowship trained neurologist, and is being treated with traditional VIM DBS therapy. Patient has no evidence of non-ET central nervous system disease or injury and has had a significantly disabling, upper extremity tremor despite ongoing VIM DBS therapy for at least three (3) months prior to DBS revision surgery. Patient has a postural or kinetic tremor severity score of at least 2 out of 4 in the extremity intended for treatment on the Fahn-Tolosa-Marin Clinical Rating Scale for Tremor (TRS) despite ongoing VIM DBS therapy. Patient has a TRS score of 2 or above in any one of the items 16-23 from the Disability subsection of the TRS: speaking, feeding other than liquids, bringing liquids to mouth, hygiene, dressing, writing, working and social activities despite ongoing VIM DBS therapy. Patient's tremor is refractory to adequate trials of at least two medications, one of which should be either propranolol or primidone. Proof of this is not required for patients with a current device that is being removed and replaced with a new device. An adequate medication trial is defined as a therapeutic dose of each medication or the development of side effects as the medication dose is titrated. Patient is available for appropriate follow-up times for the length of the study. Exclusion Criteria: Any previous neurosurgical intervention other than VIM DBS, including ablative brain lesions for tremor suppression. Medication related movement disorders. Any suspicion of Parkinson's disease, including presence of Parkinsonian features such as bradykinesia, rigidity, or postural instability. Any behaviors consistent with alcohol or substance abuse as defined by the criteria outlined in Diagnostic and Statistical Manual of Mental Disorders (DSM-V). Severe medical co-morbidity including cardiovascular disorder, lung disorder, kidney disease, continuous neurological disease, hematological disease, or frailty that impact tolerability of the surgery as judged by the screening physicians. Abnormal brain MRI including hydrocephalus, stroke, structural lesions, demyelinating lesions, or infectious lesions. Also excluded will be subjects with severe brain atrophy. Any uncontrolled symptoms or signs of increased intracranial pressure (e.g., headache, nausea, vomiting, lethargy, papilledema). A history of seizures within the past year. A dementia rating scale score (DRS) <130 signifying significant cognitive dysfunction and a potential for inability to cooperate with tasks involved in the study. Any attempt or intent of suicide during the previous six months. Presence or history of psychosis. Any person known to have abnormal coagulation or any medications which interfere with coagulation Significant untreated or unstable mood disorders including depression. This will be determined by the Neuropsychological team during FastTrack and by the Neurologist In addition, patients who are pregnant or plan to become pregnant will be excluded from this study.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Device Feasibility
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment Naive<br>Participants receiving Long-term stimulation of the thalamus via dual leads for Essential Tremor | Device: Medtronic Summit Rechargable (RC)+S<br>* Dual channel closed-loop pulse generator with connection to both new DBS leads for deep stimulation of VIM vs VO<br>Procedure: standard ET DBS<br>* Single Lead VIM<br>Procedure: ipsilateral VO<br>* second lead in the ipsilateral VO<br>|
| Active Comparator: Refractory Participants<br>Patients with recurrent, debilitating intention tremor despite ongoing, optimized VIM DBS therapy | Device: Medtronic Summit Rechargable (RC)+S<br>* Dual channel closed-loop pulse generator with connection to both new DBS leads for deep stimulation of VIM vs VO<br>Procedure: ipsilateral thalamic (VIM+VO) DBS<br>* Implantation of two new ipsilateral thalamic (VIM+VO) DBS<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy Assessment - Tremor | Tremor rating scale This 5-point scale rates tremor severity based on tremor amplitude, from 0 (no tremor) to 4 (severe tremor) in each part of the body, and includes assessments of specific abilities and functional disability. | Up to 24 months |