Use of Two Deep Brain Stimulation (DBS) Electrodes to Treat Post-Traumatic Tremor

This study has been completed.
Sponsor:
Collaborators:
Medtronic
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT00954421
First received: July 27, 2009
Last updated: July 21, 2014
Last verified: July 2014
  Purpose

The purpose of this research study is to:

  1. Determine whether deep brain stimulation (DBS) with two leads (very thin coiled wires) placed unilaterally (on one side of the brain) is beneficial to patients with multiple sclerosis (MS) tremor.
  2. Compare the two different locations of the DBS lead placement in effectiveness for treatment of muscle tremors that do not respond to treatment with medication caused by multiple sclerosis.
  3. Evaluate any side effects that may result from the two DBS leads.

Condition Intervention
Multiple Sclerosis
Device: Deep Brain Stimulation

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Use of Two DBS Electrodes to Treat Post-Traumatic Tremor

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • Fain-Tolosa-Marin Tremor Rating Scale (TRS) Change Score for Both VIM and VO ON (Baseline Minus 6 Months Post-implant) [ Time Frame: Change from Baseline to Six Months ] [ Designated as safety issue: No ]

    Tremor was evaluated using the Fain-Tolosa-Marin Tremor Rating Scale (TRS). Score was obtained by summing all 21 items, each of which assessed tremor on a scale of 0-4. Because some of the 21 items contained more than one subsection, total maximum score was 144, and minimum score was 0. Higher scores represent worse tremor.

    Both VIM and VO stimulators will be turned ON and TRS score at 6 months will be compared to pre-implant (baseline).



Secondary Outcome Measures:
  • Fain-Tolosa-Marin Tremor Rating Scale (TRS) Change Score for Either VIM or VO On, and for Both VIM and VO Off (Baseline Minus 6 Months Post-implant) [ Time Frame: Baseline to Six Months ] [ Designated as safety issue: No ]

    Tremor was evaluated using the Fain-Tolosa-Marin Tremor Rating Scale (TRS). Score was obtained by summing all 21 items, each of which assessed tremor on a scale of 0-4. Because some of the 21 items contained more than one subsection, total maximum score was 144, and minimum score was 0. Higher scores represent worse tremor.

    Both VIM and VO stimulators will be turned ON and TRS score at 6 months will be compared to pre-implant (baseline).

    Either VO or VIM stimulator will be turned on (as opposed to both stimulators, as in outcome measure 1), and change in Tremor Rating Scale scores will be compared. The effects of each individual stimulator will also be compared to both being turned on.



Enrollment: 16
Study Start Date: November 2006
Study Completion Date: December 2013
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Deep Brain Stimulation
Multiple Sclerosis Tremor treated with VIM and VO Deep Brain Stimulation
Device: Deep Brain Stimulation
Use of two ipsilateral thalamic Deep Brain Stimulation electrodes (one at the ventralis intermedius nucleus/ventralis oralis posterior nucleus border or VIM and one at the ventralis oralis anterior nucleus/ventralis oralis posterior nucleus border or VO) for treatment of disabling and medication refractory tremor secondary to head trauma or multiple sclerosis.

Detailed Description:

Surgical treatment of disabling multiple sclerosis (MS) tremor that does not respond to medication has proven difficult. To date, there have been no prospective blinded studies to evaluate efficacy of surgical treatments for these tremors. Based on prior data, this study will examine the use of 2 DBS electrodes on the same side of the brain in the thalamus region (one at an area referred to as the "ventralis intermedius nucleus/ventralis oralis posterior nucleus border," or "VIM," and one at a region called the "ventralis oralis anterior nucleus/ventralis oralis posterior nucleus border," or "VO") for treatment of MS tremor. This study will test the effectiveness of VIM combined with, and independent of, VO DBS, and characterize safety, benefits and side effects of this procedure for treatment of MS-related tremors.

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The patient must have an unequivocal diagnosis of Multiple Sclerosis (MS) resulting in disabling tremor as indicated by a score of at least 3 on the Tremor Rating Scale (TRS) baseline global assessments by the examiner and the patient.
  • The patient must have a history of an unsatisfactory response to medical management. Any patient will need to have tried and failed at least one drug from at least three of the four following medication classes: anticholinergics, muscle relaxants, benzodiazepines, and beta blockers. Alternatively, a patient may also qualify if tremor-suppressing medications are contraindicated due to a coexisting medical condition or drug allergy.
  • The MS patient must have disabling and medically refractory unilateral or bilateral upper extremity tremor. Patients with associated ipsilateral lower extremity tremor are not excluded.
  • The tremor must meet the following specific diagnostic criteria:

    • The tremor must be predominantly postural or action (versus resting) and have a rhythmic and/or ballistic characteristic.
    • The tremor may not have features that indicate a significant cerebellar etiology (i.e., non-prominent ataxia, dysdiadokokinesia, dysmetria).
    • The tremor must have been present and either stable or progressing for greater than one year.
    • The tremor must be disabling. Disabling is defined as significant impairment of the normal functions of daily life as indicated by a score of at least 5 on the Clinical Global Impression (CGI)-Severity scale.

Exclusion Criteria:

  • Significant medical disease that would excessively increase risk of peri-operative complications (significant cardiac or pulmonary disease, uncontrolled hypertension, inadequately treated major depression).
  • More than mild non-tremor cerebellar dysfunction (ataxia, dysmetria, dysdiadokokinesia).
  • Evidence of secondary/atypical movement disorder as suggested by presence of the following:

    • history of stroke(s)
    • exposure to toxins or neuroleptics
    • history of encephalitis
    • neurological signs of upper motor neuron disease, supranuclear gaze palsy, or significant orthostatic hypotension
  • MRI with significant evidence of severe brain atrophy or other prohibitive abnormalities (absence of thalamic target for Deep Brain Stimulation (DBS), lacunar infarcts, or iron deposits in the putamen).
  • Cognitive dysfunction as evidenced by a score of less than 120 on the Mattis Dementia Rating Scale (MDRS) Such patients will be excluded because significant dementia places the patient at high risk for surgery-induced deterioration of cognitive function, and such patients might have limited ability to accurately assess the impact of DBS.
  • Major psychiatric disorder on the Structured Clinical Interview (SCID-IV) for the Diagnostic and Statistical Manual Version 4 (DSM-IV). 45 Patients with Major Depression within 3 months of entry into the study will be excluded. High rates of psychiatric co-morbidity can complicate any neurosurgical study. While the cleanest study would exclude patients with psycho-pathology, we do not believe this is realistic or practical, given the majority of patients with advanced movement disorders will suffer from some degree of anxiety or depression. We will screen patients for psychiatric disorders, treat disorders prior to DBS and admit patients who are psychiatrically stable for at least 3 months prior to entry (without active psychiatric diagnosis by SCID criteria).
  • Patients with any implanted device that precludes magnetic resonance imaging (MRI) will be excluded from this study. Examples of such devices include cochlear implants, spinal cord stimulators, many cardiac pacemakers, and some older aneurysm clips
  • Patients who have a known need for future MRIs or diathermy treatments will be excluded from this study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00954421

Locations
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
Sponsors and Collaborators
University of Florida
Medtronic
Investigators
Principal Investigator: Kelly Foote, MD University of Florida
  More Information

No publications provided

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT00954421     History of Changes
Other Study ID Numbers: 461-2006, K23NS052557
Study First Received: July 27, 2009
Results First Received: April 15, 2014
Last Updated: July 21, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Multiple Sclerosis
Autoimmune Diseases
Autoimmune Diseases of the Nervous System
Demyelinating Autoimmune Diseases, CNS
Demyelinating Diseases
Immune System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on October 30, 2014