Responsive Deep Brain Stimulator for Essential Tremor

NCT02649166 | Active Not Recruiting DMC FDA Device

• 2 other identifiers: IRB201501021 -N-A5UH3NS095553-04
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Essential Tremor

Keywords

Essential tremor; Kinetic tremor; Intention tremor

Outcome Measures

Primary Outcomes (3)

• Clinical Rating Scale for Tremor (CRST) for continuous deep brain stimulation

  \- Reduction in Clinical Rating Scale for Tremor after 6 months as an effect of continuous Vim deep brain stimulation The Fahn-Tolosa-Marin Tremor Rating Scale is a clinical rating scale assessing severity of tremor by body part from 0 (none) to 4 (severe). The scale is divided into three parts, where Part A assesses tremor severity at rest, during posture, and kinetic maneuvers for nine body parts; Part B assesses ability to perform specific motor tasks/functions (writing, drawing, and pouring with dominant and nondominant hands); and Part C assesses patient-reported functional disability resulting from the tremor. Score ranges from 0 to 80 for Part A, from 0 to 36 for Part B, and from 0 to 28 for Part C. The total score obtained by adding the three parts is 144. A higher score indicates a higher severity of the tremor. Finally, the scale includes one separate item dealing with global assessment of tremor-related disability, rated by both patient and examiner on a 5-point scale.

  6 months post-surgery

• Clinical Rating Scale for Tremor (CRST) for closed-loop deep brain stimulation

  \- Closed-loop deep brain stimulation as an effective alternative to continuous deep brain stimulation Clinical scores during continuous stimulation will be compared to scores on the during closed-loop stimulation.

  Baseline until 24 months post-surgery

• Clinical Rating Scale for Tremor (CRST) for continuous deep brain stimulation

  \- Reduction in Clinical Rating Scale for Tremor after 24 months as an effect of continuous Vim deep brain stimulation

  24 months post-surgery

Study Arms (1)

Deep brain stimulation

EXPERIMENTAL

All participants will undergo unilateral deep brain stimulation (DBS) implantation for essential tremor. Medtronic Summit RC+S devices will be used because these are capable of recording brain signals, as well as delivering DBS. Participants will receive continuous (open-loop) and closed-loop deep brain stimulation interventions, which will be compared for efficacy.

Device: Deep brain stimulation; Device: Closed-loop deep brain stimulation

Interventions

Deep brain stimulation DEVICE

The deep brain stimulation system includes an implantable neurostimulator, thalamic leads to be implanted in the ventral intermediate nucleus (Vim), and subdural cortical strips. The deep brain stimulation system will be set to provide continuous stimulation for the 6 months following surgery. Subjects will be seen monthly for evaluation as a part of normal clinical care for deep brain stimulation. At 6 months, the investigators will determine whether or not the subject is a candidate for closed-loop deep brain stimulation. Qualifying subjects will have the option to have their settings changed in order to participate in the RBS stimulation intervention. These subjects will been seen every 6 months for evaluation as part of normal clinical care for deep brain stimulation.

Also known as: Medtronic Summit RC+S

Deep brain stimulation

Closed-loop deep brain stimulation DEVICE

The deep brain stimulation system includes an implantable neurostimulator, Vim thalamic leads, and subdural strips. Six months post-surgery, the deep brain stimulation system will be set to provide responsive stimulation for the duration of the study. Subjects will be seen every 6 months for evaluation as a part of normal clinical care for deep brain stimulation. Data gathered from the subject during the first 6 months will be used to determine if this intervention is applicable for each individual subject. Subjects who do not qualify will continue to receive the other study intervention.

Also known as: Medtronic Nexus-E

Deep brain stimulation

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• You provide informed consent.
• You are over 21 years of age.
• 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.
• 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).
• 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).
• 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.
• 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.
• You are available for appropriate follow-up times for the length of the study.

You may not qualify if:

• Any previous neurosurgical intervention including deep brain stimulation or ablative brain lesions.
• Medication related movement disorders.
• Any suspicion of Parkinsonian tremor, including presence of Parkinsonian features such as bradykinesia, rigidity, or postural instability.
• Any behaviors consistent with ethanol or substance abuse as defined by the criteria outlined in DSM-V.
• 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.
• Abnormal brain MRI including hydrocephalus, stroke, structural lesions, demyelinating lesions, or infectious lesions. Also excluded will be subjects with severe atrophy.
• Any uncontrolled symptoms or signs of increased intracranial pressure (e.g., headache, nausea, vomiting, lethargy, papilledema).
• A history of seizures within the past year.
• A dementia rating scale score (DRS) \<130 signifying significant cognitive dysfunction and a potential for inability to cooperate with tasks involved in the study.
• Any attempt or intent of suicide in the last six months.
• Presence or history of psychosis.
• 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:
• Scores ≥ 20 on the Patient Health Questionnaire - 9 (PHQ-9).
• Currently under the care of a psychiatrist
• Currently participating in cognitive-behavioral therapy

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• University of Florida: lead
• Medtronic: collaborator

Study Sites (1)

University of Florida

Gainesville, Florida, 32611, United States

Location

MeSH Terms

Conditions

Essential Tremor; Tremor

Interventions

Deep Brain Stimulation

Condition Hierarchy (Ancestors)

Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Dyskinesias; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Surgical Procedures, Operative

Study Officials

• Aysegul Gunduz, Ph.D

  University of Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2016
• First Posted: January 7, 2016
• Study Start: February 1, 2017
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: January 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

US (1)