Clinical trial NCT00954421: Use of Two Deep Brain Stimulation (DBS) Electrodes to Treat Post-Traumatic Tremor
Official title: Use of Two DBS Electrodes to Treat Post-Traumatic Tremor
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Multiple Sclerosis
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
name: Medtronic
First posted: 2009-08-07
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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.

Primary outcomes:
measure: Fain-Tolosa-Marin Tremor Rating Scale (TRS) Change Score for Both VIM and VO ON (Baseline Minus 6 Months Post-implant)
timeFrame: Change from Baseline to Six Months
Secondary outcomes:
measure: 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)
timeFrame: Baseline to Six Months
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
Study officials:
affiliation: University of Florida
name: Kelly Foote, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Oliveria SF, Rodriguez RL, Bowers D, Kantor D, Hilliard JD, Monari EH, Scott BM, Okun MS, Foote KD. Safety and efficacy of dual-lead thalamic deep brain stimulation for patients with treatment-refractory multiple sclerosis tremor: a single-centre, randomised, single-blind, pilot trial. Lancet Neurol. 2017 Sep;16(9):691-700. doi: 10.1016/S1474-4422(17)30166-7. Epub 2017 Jun 20.