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Responsive Deep Brain Stimulator for Essential Tremor

Primary Purpose

Essential Tremor

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Deep brain stimulation
Closed-loop deep brain stimulation
Sponsored by
University of Florida
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Essential Tremor focused on measuring Essential tremor, Kinetic tremor, Intention tremor

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. You provide informed consent.
  2. You are over 21 years of age.
  3. You are diagnosed with a postural-intention (essential) tremor for at least 3 years and meet strict diagnostic criteria and have been seen and examined by a movement disorders fellowship trained neurologist.
  4. You have had a significant disabling medical-refractory upper extremity tremor with no evidence of supraspinal central nervous system disease or injury (tremor not adequately controlled by medications for at least three (3) months before implant).
  5. You have had 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 (CRST).
  6. You have had a CRST score of 2 or above in any one of the items 16-23 from the Disability subsection of the CRST: speaking, feeding other than liquids, bringing liquids to mouth, hygiene, dressing, writing, working and social activities.
  7. Your tremor is refractory adequate trials of at least two medications, one of which should be either propranolol or primidone. 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.
  8. You are available for appropriate follow-up times for the length of the study.

Exclusion Criteria:

  1. Any previous neurosurgical intervention including deep brain stimulation or ablative brain lesions.
  2. Medication related movement disorders.
  3. Any suspicion of Parkinsonian tremor, including presence of Parkinsonian features such as bradykinesia, rigidity, or postural instability.
  4. Any behaviors consistent with ethanol or substance abuse as defined by the criteria outlined in DSM-V.
  5. 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.
  6. Abnormal brain MRI including hydrocephalus, stroke, structural lesions, demyelinating lesions, or infectious lesions. Also excluded will be subjects with severe atrophy.
  7. Any uncontrolled symptoms or signs of increased intracranial pressure (e.g., headache, nausea, vomiting, lethargy, papilledema).
  8. A history of seizures within the past year.
  9. A dementia rating scale score (DRS) <130 signifying significant cognitive dysfunction and a potential for inability to cooperate with tasks involved in the study.
  10. Any attempt or intent of suicide in the last six months.
  11. Presence or history of psychosis.

  12. Significant or active mood disorders including depression. For the purpose of this study, we consider a significant mood disorder to include any subject who has:

    1. Scores ≥ 20 on the Patient Health Questionnaire - 9 (PHQ-9).
    2. Currently under the care of a psychiatrist
    3. Currently participating in cognitive-behavioral therapy
    4. Been hospitalized for the treatment of a psychiatric illness within 12 months
    5. Ever received transcranial magnetic stimulation
    6. Ever received electroconvulsive therapy

n. In addition, patients who are pregnant or plan to become pregnant will be excluded from this study.

Sites / Locations

  • University of FloridaRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Deep brain stimulation

Arm Description

All participants will undergo unilateral deep brain stimulation (DBS) implantation for essential tremor. Medtronic Summit RC+S devices will be used because these are capable of recording brain signals, as well as delivering DBS. Participants will receive continuous (open-loop) and closed-loop deep brain stimulation interventions, which will be compared for efficacy.

Outcomes

Primary Outcome Measures

Clinical Rating Scale for Tremor (CRST) for continuous deep brain stimulation
- Reduction in Clinical Rating Scale for Tremor after 6 months as an effect of continuous Vim deep brain stimulation The Fahn-Tolosa-Marin Tremor Rating Scale is a clinical rating scale assessing severity of tremor by body part from 0 (none) to 4 (severe). The scale is divided into three parts, where Part A assesses tremor severity at rest, during posture, and kinetic maneuvers for nine body parts; Part B assesses ability to perform specific motor tasks/functions (writing, drawing, and pouring with dominant and nondominant hands); and Part C assesses patient-reported functional disability resulting from the tremor. Score ranges from 0 to 80 for Part A, from 0 to 36 for Part B, and from 0 to 28 for Part C. The total score obtained by adding the three parts is 144. A higher score indicates a higher severity of the tremor. Finally, the scale includes one separate item dealing with global assessment of tremor-related disability, rated by both patient and examiner on a 5-point scale.
Clinical Rating Scale for Tremor (CRST) for closed-loop deep brain stimulation
- Closed-loop deep brain stimulation as an effective alternative to continuous deep brain stimulation Clinical scores during continuous stimulation will be compared to scores on the during closed-loop stimulation.
Clinical Rating Scale for Tremor (CRST) for continuous deep brain stimulation
- Reduction in Clinical Rating Scale for Tremor after 24 months as an effect of continuous Vim deep brain stimulation

Secondary Outcome Measures

Full Information

First Posted
January 6, 2016
Last Updated
September 21, 2022
Sponsor
University of Florida
Collaborators
Medtronic, National Institute of Neurological Disorders and Stroke (NINDS)
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1. Study Identification

Unique Protocol Identification Number
NCT02649166
Brief Title
Responsive Deep Brain Stimulator for Essential Tremor
Official Title
Closing the Loop on Tremor: A Responsive Deep Brain Stimulator for the Treatment of Essential Tremor
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 1, 2017 (Actual)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
June 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Florida
Collaborators
Medtronic, National Institute of Neurological Disorders and Stroke (NINDS)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Essential tremor is an incurable, degenerative brain disorder that results in increasingly debilitating tremor, and afflicts an estimated 7 million people in the US. In one study, 25% of essential tremor patients were forced to change jobs or take early retirement because of tremor. Essential tremor is directly linked to progressive functional impairment, social embarrassment, and even depression. The tremor associated with essential tremor is typically slow, involves the hands (and sometimes the head and voice), worsens with intentional movements, and is insidiously progressive over many years. Deep brain stimulation has emerged as a highly effective treatment for intractable, debilitating essential tremor. However, since the intention tremor of essential tremor is typically intermittent, and commonly absent at rest, the currently available continuous deep brain stimulation may be delivering unnecessary current to the brain that increases undesirable side effects such as slurred speech and walking difficulty, and hastens the depletion of device batteries, necessitating more frequent surgical procedures to replace spent pulse generators. The overall objective of this early feasibility study is to provide preliminary data on the safety and efficacy of "closed-loop" deep brain stimulation for intention tremor using novel deep brain stimulation devices capable of continuously sensing brain activity and delivering therapeutic stimulation only when necessary to suppress tremor.
Detailed Description
The purpose of this study is to investigate brain signals related to intention tremor in essential tremor in order to deliver deep brain stimulation only when the patient is showing symptoms. By delivering stimulation only when needed, the investigators hypothesize that the treatment will be more effective, will cause fewer adverse side effects and will increase battery time of the device (reducing the number of battery replacement surgeries). Participation in this study will require extensive pre-surgical screening to determine eligibility for deep brain stimulation surgery, a deep brain stimulation surgical procedure, and regular follow-ups. Subjects will be seen monthly post surgery for 6 months. After 6 months, data will be assessed and closed-loop deep brain stimulation may be offered as a stimulation setting. If so, the stimulator settings will be changed from chronic to responsive. If not, the subject will continue to receive chronic deep brain stimulation stimulation. Subsequent visits will be scheduled every 6 months until a total of 24 months of study participation (also at month 9). At the end of the initial 24-month study period, subjects will have the choice of 1) continuing active stimulation at the current setting, 2) continuing stimulation but searching for a new setting, 3) discontinuing stimulation (turning the device off), 4) having the device removed. If the subject continues to receive active stimulation, they will be followed by the investigators and seen at yearly intervals.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Essential Tremor
Keywords
Essential tremor, Kinetic tremor, Intention tremor

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Deep brain stimulation
Arm Type
Experimental
Arm Description
All participants will undergo unilateral deep brain stimulation (DBS) implantation for essential tremor. Medtronic Summit RC+S devices will be used because these are capable of recording brain signals, as well as delivering DBS. Participants will receive continuous (open-loop) and closed-loop deep brain stimulation interventions, which will be compared for efficacy.
Intervention Type
Device
Intervention Name(s)
Deep brain stimulation
Other Intervention Name(s)
Medtronic Summit RC+S
Intervention Description
The deep brain stimulation system includes an implantable neurostimulator, thalamic leads to be implanted in the ventral intermediate nucleus (Vim), and subdural cortical strips. The deep brain stimulation system will be set to provide continuous stimulation for the 6 months following surgery. Subjects will be seen monthly for evaluation as a part of normal clinical care for deep brain stimulation. At 6 months, the investigators will determine whether or not the subject is a candidate for closed-loop deep brain stimulation. Qualifying subjects will have the option to have their settings changed in order to participate in the RBS stimulation intervention. These subjects will been seen every 6 months for evaluation as part of normal clinical care for deep brain stimulation.
Intervention Type
Device
Intervention Name(s)
Closed-loop deep brain stimulation
Other Intervention Name(s)
Medtronic Nexus-E
Intervention Description
The deep brain stimulation system includes an implantable neurostimulator, Vim thalamic leads, and subdural strips. Six months post-surgery, the deep brain stimulation system will be set to provide responsive stimulation for the duration of the study. Subjects will be seen every 6 months for evaluation as a part of normal clinical care for deep brain stimulation. Data gathered from the subject during the first 6 months will be used to determine if this intervention is applicable for each individual subject. Subjects who do not qualify will continue to receive the other study intervention.
Primary Outcome Measure Information:
Title
Clinical Rating Scale for Tremor (CRST) for continuous deep brain stimulation
Description
- Reduction in Clinical Rating Scale for Tremor after 6 months as an effect of continuous Vim deep brain stimulation The Fahn-Tolosa-Marin Tremor Rating Scale is a clinical rating scale assessing severity of tremor by body part from 0 (none) to 4 (severe). The scale is divided into three parts, where Part A assesses tremor severity at rest, during posture, and kinetic maneuvers for nine body parts; Part B assesses ability to perform specific motor tasks/functions (writing, drawing, and pouring with dominant and nondominant hands); and Part C assesses patient-reported functional disability resulting from the tremor. Score ranges from 0 to 80 for Part A, from 0 to 36 for Part B, and from 0 to 28 for Part C. The total score obtained by adding the three parts is 144. A higher score indicates a higher severity of the tremor. Finally, the scale includes one separate item dealing with global assessment of tremor-related disability, rated by both patient and examiner on a 5-point scale.
Time Frame
6 months post-surgery
Title
Clinical Rating Scale for Tremor (CRST) for closed-loop deep brain stimulation
Description
- Closed-loop deep brain stimulation as an effective alternative to continuous deep brain stimulation Clinical scores during continuous stimulation will be compared to scores on the during closed-loop stimulation.
Time Frame
Baseline until 24 months post-surgery
Title
Clinical Rating Scale for Tremor (CRST) for continuous deep brain stimulation
Description
- Reduction in Clinical Rating Scale for Tremor after 24 months as an effect of continuous Vim deep brain stimulation
Time Frame
24 months post-surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: You provide informed consent. You are over 21 years of age. You are diagnosed with a postural-intention (essential) tremor for at least 3 years and meet strict diagnostic criteria and have been seen and examined by a movement disorders fellowship trained neurologist. You have had a significant disabling medical-refractory upper extremity tremor with no evidence of supraspinal central nervous system disease or injury (tremor not adequately controlled by medications for at least three (3) months before implant). You have had 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 (CRST). You have had a CRST score of 2 or above in any one of the items 16-23 from the Disability subsection of the CRST: speaking, feeding other than liquids, bringing liquids to mouth, hygiene, dressing, writing, working and social activities. Your tremor is refractory adequate trials of at least two medications, one of which should be either propranolol or primidone. 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. You are available for appropriate follow-up times for the length of the study. Exclusion Criteria: Any previous neurosurgical intervention including deep brain stimulation or ablative brain lesions. Medication related movement disorders. Any suspicion of Parkinsonian tremor, including presence of Parkinsonian features such as bradykinesia, rigidity, or postural instability. Any behaviors consistent with ethanol or substance abuse as defined by the criteria outlined in 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 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 in the last six months. Presence or history of psychosis. Significant or active mood disorders including depression. For the purpose of this study, we consider a significant mood disorder to include any subject who has: Scores ≥ 20 on the Patient Health Questionnaire - 9 (PHQ-9). Currently under the care of a psychiatrist Currently participating in cognitive-behavioral therapy Been hospitalized for the treatment of a psychiatric illness within 12 months Ever received transcranial magnetic stimulation Ever received electroconvulsive therapy n. In addition, patients who are pregnant or plan to become pregnant will be excluded from this study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Aysegul Gunduz, Ph.D
Phone
3522736877
Email
agunduz@ufl.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Julie Segura
Phone
352-273-5566
Email
julie.segura@neurology.ufl.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Aysegul Gunduz, Ph.D
Organizational Affiliation
University of Florida
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32611
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aysegul Gunduz, PhD
Phone
352-273-6877
Email
agunduz@bme.ufl.edu

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Once 24 month follow-up is completed for all subjects, the investigators will consider data sharing requests for de-identified data.

Learn more about this trial

Responsive Deep Brain Stimulator for Essential Tremor

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