Clinical trial NCT02649166: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Essential Tremor
Keywords: Essential tremor
Kinetic tremor
Intention tremor
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: Medtronic
name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2016-01-07
Enrollment: 20
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Clinical Rating Scale for Tremor (CRST) for continuous deep brain stimulation
timeFrame: 6 months post-surgery
measure: Clinical Rating Scale for Tremor (CRST) for closed-loop deep brain stimulation
timeFrame: Baseline until 24 months post-surgery
measure: Clinical Rating Scale for Tremor (CRST) for continuous deep brain stimulation
timeFrame: 24 months post-surgery
Secondary outcomes:
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
Study officials:
affiliation: University of Florida
name: Aysegul Gunduz, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: