High-Intensity Focused Ultrasound (HIFU) for Essential Tremor
Official Title: A Continued Access Study to Evaluate the Effectiveness and Safety of ExAblate Transcranial MRgFUS Thalamotomy Treatment of Medication Refractory Essential Tremor Subjects
Purpose of the Study: The purpose of this study is to assess the safety and effectiveness of MR-guided focused ultrasound (MRgFUS) thalamotomy in patients with Essential Tremor whose medicines are not working well. The ExAblate transcranial system is the name of the device that will be used to create and send ultrasound waves through the scalp and skull precisely to a small target in the thalamus, which is a structure in the center of the brain. Essential Tremor is the most common type of tremor that affects people and it tends to run in families and cause tremors when you attempt to use your hands.
Description: Usually, people with ET are treated with medicines to control the tremors. If the medicines are not effective however, surgery can be used to treat tremors. Participants are eligible to participate in this study if they have Essential Tremor that is not well-controlled with medications, and it is severe enough to consider surgery to treat the tremors. We will measure how well the procedure works using questionnaires, neurological assessments, and tremor assessments at each study visit.
- Men and women age 22 years or older.
- Subjects who are able and willing to give consent and able to attend all study visits.
- A diagnosis of ET as confirmed from clinical history and examination by a neurologist or neurosurgeon specialized in movement disorder.
- Tremor refractory to adequate trials of at least two medications, one of which should be a first line therapy of 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.
- Following the 1-month medication stability period, subject must be on stable medication for tremor.
- The 1-Month stability period visit will be 1-month post consent date
- Vim nucleus of thalamus can be target by the ExAblate device. The thalamic region must be apparent on MRI such that targeting can be performed by measurement from a line connecting the anterior and posterior commissures of the brain.
- Able to communicate sensations during the ExAblate TcMRgFUS treatment.
- Postural or intention tremor severity score of greater than or equal to 2 in the dominant hand/arm as measured by the CRST rating scale while stable on medication.
- May have bilateral appendicular tremor.
- Significant disability due to essential tremor despite medical treatment (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]).
- Inclusion and exclusion criteria have been agreed upon by two members of the medical team.
- Subjects on stable antidepressant medications for at least 3 months may be enrolled into this study (i.e., no change in medication drug or dosage for 3 months).
- Subjects with unstable cardiac status including:
- Unstable angina pectoris on medication.
- Subjects with documented myocardial infarction within six months of protocol entry.
- Significant congestive heart failure defined with ejection fraction < 40.
- Subjects with unstable ventricular arrhythmias.
- Subjects with atrial arrhythmias that are not rate-controlled.
- Subjects exhibiting any behavior(s) consistent with ethanol or substance abuse as defined by the criteria outlined in the DSM-IV as manifested by one (or more) of the following occurring within a 12 month period:
- Recurrent substance use resulting in a failure to fulfill major role obligations at work, school, or home (such as repeated absences or poor work performance related to substance use; substance-related absences, suspensions, or expulsions from school; or neglect of children or household).
- Recurrent substance use in situations in which it is physically hazardous (such as driving an automobile or operating a machine when impaired by substance use).
- Recurrent substance-related legal problems (such as arrests for substance related disorderly conduct).
- Continued substance use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the substance (for example, arguments with spouse about consequences of intoxication and physical fights).
- Severe hypertension (diastolic BP > 100 on medication).
- Subjects with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations, etc.
- Known intolerance or allergies to the MRI contrast agent (e.g. Gadolinium or Magnevist) including advanced kidney disease.
- Patient with severely impaired renal function with estimated glomerular filtration rate <30 mL/min/1.73m2 (or per local standards should that be more restrictive) and/or who is on dialysis.
- History of abnormal bleeding and/or coagulopathy.
- Receiving anticoagulant (e.g. warfarin) or antiplatelet (e.g. aspirin) therapy within one week of focused ultrasound procedure or drugs known to increase risk or hemorrhage (e.g. Avastin) within one month of focused ultrasound procedure.
- Active or suspected acute or chronic uncontrolled infection.
- History of immunocompromise including those who are HIV positive.
- History of intracranial hemorrhage.
- Cerebrovascular disease (multiple CVA or CVA within 6 months).
- Subjects with uncontrolled symptoms and signs of increased intracranial pressure (e.g., headache, nausea, vomiting, lethargy, papilledema).
- Individuals who are not able or willing to tolerate the required prolonged stationary supine position during treatment (can be up to 4 hrs of total table time).
- Are participating or have participated in another clinical trial in the last 30 days.
- Significant claustrophobia that cannot be managed with mild medication.
- Subjects unable to communicate with the investigator and staff.
- Presence of any other neurodegenerative disease such as Parkinson-plus syndromes suspected on neurological examination. These include: multisystem atrophy, progressive supranuclear palsy, dementia with Lewy bodies, and Alzheimer’s disease.
- Anyone suspected to have the diagnosis of idiopathic Parkinson’s disease.
- Anyone with the presence of parkinsonian features including bradykinesia, rigidity, or postural instability will be excluded. Subjects who exhibit only mild resting tremor but no other symptoms or signs of PD may be included.
- Presence of significant cognitive impairment as determined with a score ≤ 24 on the Mini Mental Status Examination (MMSE).
- Subjects with life-threatening systemic disease that include and not limited to the following will be excluded from the study participation: HIV, Liver Failure, blood dyscrasias, etc.
- Subjects with a history of seizures within the past year.
- Subjects with presence or history of psychosis will be excluded. Subjects with significant or active mood disorders including depression will be excluded. For purpose of this study, we consider a significant mood disorder to include any subject who:
- Scores ≥ 20 on the PHQ-9 questionnaire.
- Is currently under the care of a psychiatrist.
- Is currently participating in cognitive-behavioral therapy.
- Has been hospitalized for the treatment of a psychiatric illness within 12 months.
- Has ever received transcranial magnetic stimulation.
- Has ever received electroconvulsive therapy.
- Subjects with risk factors for intraoperative or postoperative bleeding: platelet count less than 100,000 per cubic millimeter, INR coagulation studies exceeding local institution laboratory standards, or a documented coagulopathy.
- Subjects with brain tumors.
- Any illness that in the investigator's opinion preclude participation in this study.
- Pregnancy or lactation.
- Legal incapacity or limited legal capacity.
- Subjects who have had deep brain stimulation or a prior stereotactic ablation of the basal ganglia.
- Subjects who have been administered botulinum toxins into the arm, neck, or face for 5 months prior to Baseline.
- Subjects who have an Overall Skull Density Ratio of 0.45 (±0.05) or less as calculated from the screening CT.
Study Status: Enrolling
Principal Investigator: Dr. Ali Rezai
Contact: Amelia Hargrove
Funding/Study Sponsor: InSightec