Deep Brain Stimulation (DBS) for the Suppression of Tremor

Not Applicable

Completed

Conditions: Tremor
Action Tremor
Tremor, Limb
Essential Tremor

Interventions: Device: ANS Totally Implantable Deep Brain Stimulation System

Registration Number: NCT02087046

Lead Sponsor: Abbott Medical Devices

Brief Summary: The purpose of the proposed study is to demonstrate the safety and efficacy of the ANS Totally Implantable Deep Brain Stimulation System in the VIM nucleus of the thalamus implanted for the treatment of tremor due to essential tremor.

This study will be included in the Pre-Market Approval Application to support the safety of this device in use.

Detailed Description: This study is designed as a prospective, multi-centered study for 365 days in duration from device implantation. A maximum of 12 sites will enroll 160 patients.

Each patient will be screened and then undergo a baseline evaluation followed by unilateral or bilateral implantation of the DBS system. During the implantation procedure, each patient will undergo a trial of stimulation in the operating room. The device may be internalized after a successful intra-operative trial or at a later surgery (no later than 4 weeks after initial lead placement). If the device is not activated immediately postsurgery, the patient may return to the clinic to determine optimum stimulation programming. Device programming will be optimized in as many visits as necessary following implantation. The day that the device is fully implanted will be classified as "Day 0" for each patient.

After "Day 0" the patient will return to clinic for evaluations at, Day 90 (±14 days), and Day 180 (±14 days) and Day 365 (approximately 12 months ± 30 days after Day 0). These evaluations consist of the CRST, the QUEST, the SF36, Patient and caregiver Global Ratings and the Patient Satisfaction Rating.

At Baseline and Day 180, the CRST evaluation session will be video recorded for analysis by an independent evaluator unaware of the functioning of the device. Additionally, at the Day 180 visit, the physician will have the option to provide the patient with amplitude control. A comparison of measures within the same person from pre-treatment to post-treatment will be performed. Also, pre-treatment and post-treatment group means and standard deviations will be determined.

Patients completed follow-up visits as part of the original protocol (C-04-02) for one year (or in some cases longer if patient was bilaterally implanted) and continued to complete additional visits as part of the Long-Term Follow-up protocol (C-06-03) for up to 5 years post implant.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 127

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Stimulation	ANS Totally Implantable Deep Brain Stimulation System	ANS Totally Implantable Deep Brain Stimulation System

Primary Outcome Measures

Name	Time	Method
Primary Safety Endpoint: Percentage of Participants With Device-related or Procedure Related Adverse Events	Within 180 days following the initial implant	Percentage of device-related or procedure related adverse events will be assessed within 6 months following the initial unilateral implant. All such adverse events will be counted for 180 days following surgery or until the day of the second implant, which ever comes first.
Primary Efficacy Endpoint: Difference in the Postural Tremor Score of the Target Limb Between Stimulation On and Stimulation Off, As Assessed by the Blind Reviewer	Day 180	The Fahn, Tolosa, Marin Tremor Rating Scale (referred to as the CRST), is a rating tool to assess the severity of postural, isometric, kinetic and task specific tremor in the dominant and non-dominant sides of the head, trunk and limbs of patients with ET. The CRST utilizes a 0 to 4 point scale where 0 indicates non-symptomatic (normal) and 4 indicates the most severe rating of the patient's tremor symptoms.

Secondary Outcome Measures

Name	Time	Method
Global Assessment by Patient	Day 365	Global outcome measures are a self-rated questionnaire in which patients assess their own global outcome at each visit
Clinical Rating Scale for Tremor (CRST) Evaluation- Target Limb Responder Analysis, As Assessed by the Site Physician	Day 365	The Fahn, Tolosa, Marin Tremor Rating Scale (referred to as the CRST), is a rating tool to assess the severity of postural, isometric, kinetic and task specific tremor in the dominant and non-dominant sides of the head, trunk and limbs of patients with ET. The CRST utilizes a 0 to 4 point scale where 0 indicates non-symptomatic (normal) and 4 indicates the most severe rating of the patient's tremor symptoms. During responder analysis, a 2-point reduction in kinetic tremor or postural tremor between stimulation Off and stimulation On show an improvement in activities of daily living was considered a response, was also performed using the site physician's ratings.
Clinical Rating Scale for Tremor (CRST) Evaluation- Mean Handwriting for Target Side Severity Score, As Assessed by the Blind Reviewer	Day 180	The Fahn, Tolosa, Marin Tremor Rating Scale (referred to as the CRST), is a rating tool to assess the severity of postural, isometric, kinetic and task specific tremor in the dominant and non-dominant sides of the head, trunk and limbs of patients with ET. The CRST utilizes a 0 to 4 point scale where 0 indicates non-symptomatic (normal) and 4 indicates the most severe rating of the patient's tremor symptoms. The blind reviewer will evaluate the patient's handwriting according to the CRST (scale 0-4).
Clinical Rating Scale for Tremor (CRST) Evaluation- Mean Target Limb Severity Score, As Assessed by the Site Physician	Day 365	The Fahn, Tolosa, Marin Tremor Rating Scale (referred to as the CRST), is a rating tool to assess the severity of postural, isometric, kinetic and task specific tremor in the dominant and non-dominant sides of the head, trunk and limbs of patients with ET. The CRST utilizes a 0 to 4 point scale where 0 indicates non-symptomatic (normal) and 4 indicates the most severe rating of the patient's tremor symptoms.
Number of Participants Who Would Choose to Receive the DBS System Again	Day 365	At each visit, patients will be asked if they would undergo the DBS procedure again
Change From Baseline in Beck Depression Inventory II (BDI - II) Score for Depression Symptoms	Day 365	The Beck Depression Inventory II is A clinical rating scale designed for detecting depression based on the Diagnostic and Statistical Manual of Mental Health Disorders-Fourth Edition (DSM-IV) criteria. This widely used instrument consists of 21 items to assess the intensity of depression in clinical and normal patients. Each item is a list of four statements arranged in increasing severity about a particular symptom of depression. The BDI II questionnaire contains 21 questions, each answer being scored on a scale value of 0 to 3. A score between 0-13 indicates minimal depression, 14-19 mild depression, 20-28 moderate depression and 29-63 severe depression. Total scores are obtained by computing the sum of each score. The scores range from 0 to 63, with higher score indicating greater severity of depressive symptoms.
Change From Baseline in Mini Mental State Exam (MMSE) For Examination of Mental Status	Day 365	The Mini-Mental State Examination (MMSE) is a 30-point questionnaire that is used extensively in clinical and research settings to measure cognitive impairment. It examines functions including registration (repeating named prompts), attention and calculation, recall, language, ability to follow simple commands and orientation. Any score of 24 or more (out of 30) indicates a normal cognition.
Clinical Rating Scale for Tremor (CRST) Evaluation- Pouring Ability From Target Side Severity Scores, As Assessed by the Blind Reviewer	Day 180	The Fahn, Tolosa, Marin Tremor Rating Scale (referred to as the CRST), is a rating tool to assess the severity of postural, isometric, kinetic and task specific tremor in the dominant and non-dominant sides of the head, trunk and limbs of patients with ET. The CRST utilizes a 0 to 4 point scale where 0 indicates non-symptomatic (normal) and 4 indicates the most severe rating of the patient's tremor symptoms. The blind reviewer will evaluate the patient's pouring ability according to the CRST
Clinical Rating Scale for Tremor (CRST) Evaluation-Bilateral Stimulation, As Assessed by the Site Physician	Following 180 days of stimulation	The Fahn, Tolosa, Marin Tremor Rating Scale (referred to as the CRST), is a rating tool to assess the severity of postural, isometric, kinetic and task specific tremor in the dominant and non-dominant sides of the head, trunk and limbs of patients with ET. The CRST utilizes a 0 to 4 point scale where 0 indicates non-symptomatic (normal) and 4 indicates the most severe rating of the patient's tremor symptoms. For those patients that had bilateral stimulation, the site physician will evaluate the patient's non-target side after 180 days of bilateral stimulation.
Number of Participants Who Would Recommend the DBS System	Day 365	At each visit, patients will be asked if they would recommend the DBS system to others
Clinical Rating Scale for Tremor (CRST) Evaluation- Mean Pouring From Target Side Severity Scores, As Assessed by the Site Physician	Day 180	The Fahn, Tolosa, Marin Tremor Rating Scale (referred to as the CRST), is a rating tool to assess the severity of postural, isometric, kinetic and task specific tremor in the dominant and non-dominant sides of the head, trunk and limbs of patients with ET. The CRST utilizes a 0 to 4 point scale where 0 indicates non-symptomatic (normal) and 4 indicates the most severe rating of the patient's tremor symptoms. The site physician will evaluate the patient's pouring ability according to the CRST
Clinical Rating Scale for Tremor (CRST) Evaluation-Mean Pouring From Target Side Severity Scores, As Assessed by the Site Physician	Day 365	The Fahn, Tolosa, Marin Tremor Rating Scale (referred to as the CRST), is a rating tool to assess the severity of postural, isometric, kinetic and task specific tremor in the dominant and non-dominant sides of the head, trunk and limbs of patients with ET. The CRST utilizes a 0 to 4 point scale where 0 indicates non-symptomatic (normal) and 4 indicates the most severe rating of the patient's tremor symptoms. The site physician will evaluate the patient's pouring ability according to the CRST
SF36 Components and Individual Domains	Day 365	The SF-36 questionnaire is a measure of health status with 36 items across 8 domains. The eight domains are separated into two summary scores of four domains, the physical component summary (PCS) and mental component summary (MCS). The SF-36 score is transformed into a scale of 0-100, with 100 indicating no disability. PCS and MCS are scaled in comparison to population norms to reflect a mean of 50 and standard deviation of 10 for the general population of the United States.
Clinical Rating Scale for Tremor (CRST) Evaluation- Mean Handwriting for Target Side Severity Score, As Assessed by the Site Physician	Day 365	The Fahn, Tolosa, Marin Tremor Rating Scale (referred to as the CRST), is a rating tool to assess the severity of postural, isometric, kinetic and task specific tremor in the dominant and non-dominant sides of the head, trunk and limbs of patients with ET. The CRST utilizes a 0 to 4 point scale where 0 indicates non-symptomatic (normal) and 4 indicates the most severe rating of the patient's tremor symptoms. The site physician will evaluate the patient's handwriting according to the CRST (scale 0-4).
Clinical Rating Scale for Tremor (CRST) Evaluation- Mean Total Motor Score, As Assessed by the Site Physician	Day 365	The Fahn, Tolosa, Marin Tremor Rating Scale (referred to as the CRST), is a rating tool to assess the severity of postural, isometric, kinetic and task specific tremor in the dominant and non-dominant sides of the head, trunk and limbs of patients with ET. The CRST utilizes a 0 to 4 point scale where 0 indicates non-symptomatic (normal) and 4 indicates the most severe rating of the patient's tremor symptoms. The motor score adds together all responses to the tremor assessment for questions 1-9 of the CRST (whether or not the specific side is being treated).
Quality of Life in Essential Tremor (QUEST): Overall Summary Index	Baseline	The QUEST questionnaire consists of 30 items, which are rated from 0 to 4, corresponding to the frequency (from never to always). Those 30 items assess how tremor impacts a function or how it can be associated with feelings or attitudes. The 30 items contribute to five sub scales (number of items contributing to each scale in parentheses): Physical/ADL (9), Psychosocial (9), Communication (3), Hobbies/Leisure (3), and Work/Finances (6). The score on each sub scale is expressed as a percentage of the total score possible, with a higher score indicating greater dissatisfaction with that domain of QOL. As the scores were expressed as percentages, if a question was unanswered it was excluded and percentages were calculated based on the remaining answers. A total or quest summary index (QSI) was computed by calculating the mean of the five scales. Maximal score of 100 indicates worse quality of life, while minimal score 0 corresponds to best quality of life.
Global Assessment Scores by Examiner	Day 365	Global outcome measures are a self-rated questionnaire that measures a global assessment of the patient quality of life and the examiner's interpretation of the patient's quality of life.
Mini Mental State Exam (MMSE) for Examination of Mental Status	Baseline	The Mini-Mental State Examination (MMSE) is a 30-point questionnaire that is used extensively in clinical and research settings to measure cognitive impairment. It examines functions including registration (repeating named prompts), attention and calculation, recall, language, ability to follow simple commands and orientation. Any score of 24 or more (out of 30) indicates a normal cognition.
Clinical Rating Scale for Tremor (CRST) Evaluation- Activity of Daily Living Score, As Assessed by the Site Physician	Day 365	The Fahn, Tolosa, Marin Tremor Rating Scale (referred to as the CRST), is a rating tool to assess the severity of postural, isometric, kinetic and task specific tremor in the dominant and non-dominant sides of the head, trunk and limbs of patients with ET. The CRST utilizes a 0 to 4 point scale where 0 indicates non-symptomatic (normal) and 4 indicates the most severe rating of the patient's tremor symptoms. The activity of daily living score adds together all responses to questions 15-21 of the CRST.
Clinical Rating Scale for Tremor (CRST) Evaluation-Non-Target Limb Severity Scores, As Assessed by the Site Physician	Following 180 days of stimulation	The Fahn, Tolosa, Marin Tremor Rating Scale (referred to as the CRST), is a rating tool to assess the severity of postural, isometric, kinetic and task specific tremor in the dominant and non-dominant sides of the head, trunk and limbs of patients with ET. The CRST utilizes a 0 to 4 point scale where 0 indicates non-symptomatic (normal) and 4 indicates the most severe rating of the patient's tremor symptoms. For those patients that had bilateral stimulation, the site physician will evaluate the patient's non-target side after 180 days with only the second side system On
Change From Baseline for Quality of Life in Essential Tremor (QUEST): Overall Summary Index	Day 365	The QUEST questionnaire consists of 30 items, which are rated from 0 to 4, corresponding to the frequency (from never to always). Those 30 items assess how tremor impacts a function or how it can be associated with feelings or attitudes. The 30 items contribute to five sub scales (number of items contributing to each scale in parentheses): Physical/ADL (9), Psychosocial (9), Communication (3), Hobbies/Leisure (3), and Work/Finances (6). The score on each sub scale is expressed as a percentage of the total score possible, with a higher score indicating greater dissatisfaction with that domain of QOL. As the scores were expressed as percentages, if a question was unanswered it was excluded and percentages were calculated based on the remaining answers. A total or quest summary index (QSI) was computed by calculating the mean of the five scales. Maximal score of 100 indicates worse quality of life, while minimal score 0 corresponds to best quality of life.
Global Assessment by Caregiver	Day 365	Global outcome measures are a self-rated questionnaire that measures a global assessment of the patient quality of life and the caregiver's interpretation of the patient's quality of life
Beck Depression Inventory II (BDI - II) Score for Depression Symptoms	Baseline	The Beck Depression Inventory II is A clinical rating scale designed for detecting depression based on the Diagnostic and Statistical Manual of Mental Health Disorders-Fourth Edition (DSM-IV) criteria. This widely used instrument consists of 21 items to assess the intensity of depression in clinical and normal patients. Each item is a list of four statements arranged in increasing severity about a particular symptom of depression. The BDI II questionnaire contains 21 questions, each answer being scored on a scale value of 0 to 3. A score between 0-13 indicates minimal depression, 14-19 mild depression, 20-28 moderate depression and 29-63 severe depression. Total scores are obtained by computing the sum of each score. The scores range from 0 to 63, with higher score indicating greater severity of depressive symptoms.
Subjective Assessment by Patient Since Activation of System	Day 365	Subjective assessment includes changes in their ET symptoms since the last visit indicated as marked improvement, moderate improvement, mild improvement, worsening, or no change.
Number of Participants With Satisfaction With the DBS System's Functioning and Ability to Control Symptoms	Day 365	At each visit, patients will be asked about their satisfaction with the DBS system's functioning and ability to control symptoms

Trial Locations

Locations (12): University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Loma Linda University School of Medicine
🇺🇸
Loma Linda, California, United States
Pacific Hills Neurosurgery Medical Group
🇺🇸
Pasadena, California, United States
Mayo Clinic
🇺🇸
Jacksonville, Florida, United States
University of Florida
🇺🇸
Gainesville, Florida, United States
Columbia University Medical Center
🇺🇸
New York, New York, United States
Oakwood Hospital
🇺🇸
Dearborn, Michigan, United States
Vanderbilt University
🇺🇸
Nashville, Tennessee, United States
Neurology Specialists of Dallas
🇺🇸
Dallas, Texas, United States
Baylor College of Medicine
🇺🇸
Houston, Texas, United States
University of San Francisco
🇺🇸
San Francisco, California, United States
University of Rochester
🇺🇸
Rochester, New York, United States