Clinical trial NCT02087046: Deep Brain Stimulation (DBS) for the Suppression of Tremor
Official title: A Clinical Evaluation of the Advanced Neuromodulation System (ANS) Totally Implantable Deep Brain Stimulation System for the Suppression of Tremor in the Upper Extremities of Patients With Essential Tremor.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Tremor
Action Tremor
Essential Tremor
Tremor, Limb
Lead sponsor: Abbott Medical Devices
Sponsor class: INDUSTRY
First posted: 2014-03-14
Enrollment: 127
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion criteria:

1. Patient or authorized representative has signed an informed consent.
2. Patient is over 18 years of age.
3. Patient is diagnosed with essential tremor for at least 3 years.
4. Patient has a 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. Patient has a postural or kinetic tremor severity score of at least 3 out of 4 in the extremity intended for treatment on the Fahn-Tolosa-Marin Clinical Rating Scale for Tremor.
6. Patient will maintain a constant dose of anti-tremor medication indicated as best medical management for one (1) month prior to enrollment in study.
7. Patient is available for appropriate follow-up times for the length of the study.

Exclusion criteria:

1. Patient is not surgical candidate;
2. Patient has other clinically or medically significant disease;
3. Patient has any neurological injury or disease other than essential tremor;
4. Patient has any condition requiring repeated MRI scans;
5. Patient has any condition requiring diathermy;
6. Patients on anticoagulant medications;
7. Patient has untreated clinically significant depression;
8. Patient has had an electrical or electromagnetic implant (cochlear prosthesis, pacemaker etc);
9. Patient has had a prior thalamotomy or surgical ablation procedure in either side of the brain;
10. Patient has dementia interfering with their ability to co-operate or comply with study requirements or comprehend the informed consent (mini-mental exam score \<24);
11. Patient abuses drugs or alcohol;
12. Patient has had botulinum toxin injections in the six (6) months prior to enrollment;
13. Patient has a history of cranial surgery;
14. Patient has a history of seizures;
15. Patient has any metallic implants that may interfere with the functioning of the device (e.g. aneurysm clips);
16. Patient has a history of stimulation intolerance in any area of the body;
17. Patient is a female of child bearing potential with a positive urine pregnancy test or not using adequate contraception.

Primary outcomes:
measure: 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
timeFrame: Day 180
measure: Primary Safety Endpoint: Percentage of Participants With Device-related or Procedure Related Adverse Events
timeFrame: Within 180 days following the initial implant
Secondary outcomes:
measure: Clinical Rating Scale for Tremor (CRST) Evaluation- Mean Target Limb Severity Score, As Assessed by the Site Physician
timeFrame: Baseline
measure: Clinical Rating Scale for Tremor (CRST) Evaluation- Mean Target Limb Severity Score, As Assessed by the Site Physician
timeFrame: Day 90
measure: Clinical Rating Scale for Tremor (CRST) Evaluation- Mean Target Limb Severity Score, As Assessed by the Site Physician
timeFrame: Day 180
measure: Clinical Rating Scale for Tremor (CRST) Evaluation- Mean Target Limb Severity Score, As Assessed by the Site Physician
timeFrame: Day 365
measure: Clinical Rating Scale for Tremor (CRST) Evaluation- Target Limb Responder Analysis, As Assessed by the Site Physician
timeFrame: Day 90
measure: Clinical Rating Scale for Tremor (CRST) Evaluation- Target Limb Responder Analysis, As Assessed by the Site Physician
timeFrame: Day 180
measure: Clinical Rating Scale for Tremor (CRST) Evaluation- Target Limb Responder Analysis, As Assessed by the Site Physician
timeFrame: Day 365
measure: Clinical Rating Scale for Tremor (CRST) Evaluation- Mean Handwriting for Target Side Severity Score, As Assessed by the Site Physician
timeFrame: Baseline
measure: Clinical Rating Scale for Tremor (CRST) Evaluation- Mean Handwriting for Target Side Severity Score, As Assessed by the Site Physician
timeFrame: Day 90
measure: Clinical Rating Scale for Tremor (CRST) Evaluation- Mean Handwriting for Target Side Severity Score, As Assessed by the Site Physician
timeFrame: Day 180
measure: Clinical Rating Scale for Tremor (CRST) Evaluation- Mean Handwriting for Target Side Severity Score, As Assessed by the Site Physician
timeFrame: Day 365
measure: Clinical Rating Scale for Tremor (CRST) Evaluation- Mean Handwriting for Target Side Severity Score, As Assessed by the Blind Reviewer
timeFrame: Day 180
measure: Clinical Rating Scale for Tremor (CRST) Evaluation- Mean Pouring From Target Side Severity Scores, As Assessed by the Site Physician
timeFrame: Baseline
measure: Clinical Rating Scale for Tremor (CRST) Evaluation-Mean Pouring From Target Side Severity Scores, As Assessed by the Site Physician
timeFrame: Day 90
measure: Clinical Rating Scale for Tremor (CRST) Evaluation- Mean Pouring From Target Side Severity Scores, As Assessed by the Site Physician
timeFrame: Day 180
measure: Clinical Rating Scale for Tremor (CRST) Evaluation-Mean Pouring From Target Side Severity Scores, As Assessed by the Site Physician
timeFrame: Day 365
measure: Clinical Rating Scale for Tremor (CRST) Evaluation- Pouring Ability From Target Side Severity Scores, As Assessed by the Blind Reviewer
timeFrame: Day 180
measure: Clinical Rating Scale for Tremor (CRST) Evaluation- Mean Total Motor Score, As Assessed by the Site Physician
timeFrame: Baseline
measure: Clinical Rating Scale for Tremor (CRST) Evaluation- Mean Total Motor Score, As Assessed by the Site Physician
timeFrame: Day 90
measure: Clinical Rating Scale for Tremor (CRST) Evaluation- Mean Total Motor Score, As Assessed by the Site Physician
timeFrame: Day 180
measure: Clinical Rating Scale for Tremor (CRST) Evaluation- Mean Total Motor Score, As Assessed by the Site Physician
timeFrame: Day 365
measure: Clinical Rating Scale for Tremor (CRST) Evaluation- Activity of Daily Living Score, As Assessed by the Site Physician
timeFrame: Baseline
measure: Clinical Rating Scale for Tremor (CRST) Evaluation- Activity of Daily Living Score, As Assessed by the Site Physician
timeFrame: Day 90
measure: Clinical Rating Scale for Tremor (CRST) Evaluation- Activity of Daily Living Score, As Assessed by the Site Physician
timeFrame: Day 180
measure: Clinical Rating Scale for Tremor (CRST) Evaluation- Activity of Daily Living Score, As Assessed by the Site Physician
timeFrame: Day 365
measure: Clinical Rating Scale for Tremor (CRST) Evaluation-Bilateral Stimulation, As Assessed by the Site Physician
timeFrame: Baseline
measure: Clinical Rating Scale for Tremor (CRST) Evaluation-Bilateral Stimulation, As Assessed by the Site Physician
timeFrame: Following 180 days of stimulation
measure: Clinical Rating Scale for Tremor (CRST) Evaluation-Non-Target Limb Severity Scores, As Assessed by the Site Physician
timeFrame: Baseline
measure: Clinical Rating Scale for Tremor (CRST) Evaluation-Non-Target Limb Severity Scores, As Assessed by the Site Physician
timeFrame: Following 180 days of stimulation
measure: Quality of Life in Essential Tremor (QUEST): Overall Summary Index
timeFrame: Baseline
measure: Change From Baseline for Quality of Life in Essential Tremor (QUEST): Overall Summary Index
timeFrame: Day 90
measure: Change From Baseline for Quality of Life in Essential Tremor (QUEST): Overall Summary Index
timeFrame: Day 180
measure: Change From Baseline for Quality of Life in Essential Tremor (QUEST): Overall Summary Index
timeFrame: Day 365
measure: SF36 Components and Individual Domains
timeFrame: Baseline
measure: SF36 Components and Individual Domains
timeFrame: Day 90
measure: SF36 Components and Individual Domains
timeFrame: Day 180
measure: SF36 Components and Individual Domains
timeFrame: Day 365
measure: Global Assessment Scores by Examiner
timeFrame: Baseline
measure: Global Assessment Scores by Examiner
timeFrame: Day 90
measure: Global Assessment Scores by Examiner
timeFrame: Day 180
measure: Global Assessment Scores by Examiner
timeFrame: Day 365
measure: Global Assessment by Caregiver
timeFrame: Baseline
measure: Global Assessment by Caregiver
timeFrame: Day 90
measure: Global Assessment by Caregiver
timeFrame: Day 180
measure: Global Assessment by Caregiver
timeFrame: Day 365
measure: Global Assessment by Patient
timeFrame: Baseline
measure: Global Assessment by Patient
timeFrame: Day 90
measure: Global Assessment by Patient
timeFrame: Day 180
measure: Global Assessment by Patient
timeFrame: Day 365
measure: Subjective Assessment by Patient Since Activation of System
timeFrame: Day 90
measure: Subjective Assessment by Patient Since Activation of System
timeFrame: Day 180
measure: Subjective Assessment by Patient Since Activation of System
timeFrame: Day 365
measure: Number of Participants With Satisfaction With the DBS System's Functioning and Ability to Control Symptoms
timeFrame: Day 90
measure: Number of Participants With Satisfaction With the DBS System's Functioning and Ability to Control Symptoms
timeFrame: Day 180
measure: Number of Participants With Satisfaction With the DBS System's Functioning and Ability to Control Symptoms
timeFrame: Day 365
measure: Number of Participants Who Would Choose to Receive the DBS System Again
timeFrame: Day 90
measure: Number of Participants Who Would Choose to Receive the DBS System Again
timeFrame: Day 180
measure: Number of Participants Who Would Choose to Receive the DBS System Again
timeFrame: Day 365
measure: Number of Participants Who Would Recommend the DBS System
timeFrame: Day 90
measure: Number of Participants Who Would Recommend the DBS System
timeFrame: Day 180
measure: Number of Participants Who Would Recommend the DBS System
timeFrame: Day 365
measure: Beck Depression Inventory II (BDI - II) Score for Depression Symptoms
timeFrame: Baseline
measure: Change From Baseline in Beck Depression Inventory II (BDI - II) Score for Depression Symptoms
timeFrame: Day 365
measure: Mini Mental State Exam (MMSE) for Examination of Mental Status
timeFrame: Baseline
measure: Change From Baseline in Mini Mental State Exam (MMSE) For Examination of Mental Status
timeFrame: Day 365
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Loma Linda
country: United States
facility: Loma Linda University School of Medicine
state: California
city: Pasadena
country: United States
facility: Pacific Hills Neurosurgery Medical Group
state: California
city: San Francisco
country: United States
facility: University of San Francisco
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Dearborn
country: United States
facility: Oakwood Hospital
state: Michigan
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Dallas
country: United States
facility: Neurology Specialists of Dallas
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
affiliation: Abbott
name: Edward Karst
role: STUDY_DIRECTOR
References: