Clinical trial: A Second Magnetic Resonance Guided Focused Ultrasound Thalamotomy for Essential Tremor (NCT04720469)

Eligibility criteria:
Inclusion Criteria:

          1. Individuals aged 22 years or older;

          2. Subjects who are able and willing to give consent and able to attend all study visits
             and MRgFUS procedure, understanding the associated risks, benefits, and alternative
             treatments;

          3. Diagnosis of ET as confirmed from clinical history and examination by a neurologist or
             neurosurgeon and unilateral MRgFUS thalamotomy at least 48 weeks prior;

          4. On a stable dose of medication for tremor for at least 4 weeks;

          5. Medication-refractory criterion: 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;

          6. Moderate-severe tremor severity criteria in the untreated hand: Despite medical
             treatment, untreated hand score of ≥2 points in the postural or intention component of
             the item 5 or 6 in the Part A of CRST, AND untreated hand score of ≥2 points in any
             one of the items 12-15 of the Part B of CRST;

          7. Disability criterion: ≥2 points in any one of the Part C items 17-23 as measured by
             the CRST;

          8. Able to communicate sensations during the MRgFUS treatment and to press the device
             STOP button.

        Exclusion Criteria:

          1. Patients with standard contraindications for MR imaging such as non-MRI compatible
             implanted metallic devices including cardiac pacemakers, size limitations, etc;

          2. Women who are pregnant;

          3. Gait subscore ≥2 points in the SARA scale;

          4. Speech subscore ≥2 points in the SARA scale;

          5. Patients with advanced kidney disease (with estimated glomerular filtration rate <30
             mL/min/1.73m2) or on dialysis;

          6. Patients with unstable cardiac status or severe hypertension including:

               1. Documented myocardial infarction within six months of enrollment

               2. Unstable angina on medication

               3. Unstable or worsening congestive heart failure

               4. Left ventricular ejection fraction below the lower limit of normal

               5. History of a hemodynamically unstable cardiac arrhythmia

               6. Cardiac pacemaker

               7. Severe hypertension (diastolic BP > 100 on medication);

          7. Patients exhibiting any behaviour(s) or clinical assessment consistent with ethanol or
             substance abuse;

          8. Patients with history of abnormal bleeding, hemorrhage, and/or coagulopathy defined as
             abnormal coagulation profile (platelet < 100,00/μl), PT (>14 sec) or PTT (>36 sec),
             and INR > 1.3;

          9. 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;

         10. Ischemic or hemorrhagic stroke within 6 months;

         11. Patients with brain tumors;

         12. Individuals who are not able or unwilling to tolerate the required prolonged
             stationary position during treatment (approximately 2-3 hours);

         13. Patients who are currently participating in another clinical investigation with an
             active treatment arm;

         14. Patients who have had deep brain stimulation (DBS) or a prior stereotactic ablation of
             the basal ganglia with GKRS or radiofrequency;

         15. Patients who have been administered botulinum toxins into the arm for 5 months prior
             to baseline.

         16. Evidence of clinically important movement disorder, such as chorea, dystonia, or
             parkinsonism. 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 Parkinson's disease may be
             included.

         17. Symptoms and signs of increased intracranial pressure (e.g. headache, nausea,
             vomiting, lethargy, and papilledema);

         18. Untreated, uncontrolled sleep apnea;

         19. Presence of any other neurodegenerative disease like multisystem atrophy, progressive
             supranuclear palsy, dementia with Lewy bodies, and Alzheimer's disease;

         20. Mild cognitive impairment with impairment in the domain of language as determined by
             screening neuropsychological battery and judged by study neuropsychologist;

         21. A known diagnosis of dementia of any cause;

         22. Uncontrolled major psychiatric disorder or suicidal ideation. Patients with
             psychiatric disorders identified on initial screening can be treated for these
             conditions before MRgFUS treatment and enrolled if deemed psychiatrically stable for
             at least three months before study entry. Any presence of psychosis will be excluded;

         23. Any illness that in the investigator's opinion preclude participation in this study;

         24. Patients with a history of seizures within the past year.

         25. Inability to generate a thermal thalamic lesion during the first MRgFUS procedure;

         26. Poor tolerance to the first MRgFUS procedure;

         27. Severe adverse event or moderate-severe adverse event related to the MRgFUS procedure
             or thalamotomy, such as clinically significant and permanent speech, language,
             sensory, motor or gait dysfunction.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 22 Years old.


Patient description (medical language): A 60-year-old man comes to the clinic complaining of hand tremor that started few months ago.  It is most bothering when he wants to drink from a glass or pour from a bottle. He does not smoke, but drinks occasionally. He recently started consuming more alcohol as his tremor subsides somewhat when he drinks small amounts of alcohol.  Family history is significant for similar problems in his mother.  Vital signs are normal and the patient has no other medical conditions.  Neurologic examination shows bilateral tremor in the upper extremities. The diagnosis of essential tremor is confirmed.

Patient description (patient's own words): I'm only a 60 years old man but I already suffer from shaky hands. It started a few months ago, and it really bothers me when I want to pour myself a glass or even while drinking. I don't smoke, but I drink alcohol from time to time. To be honest, I've been drinking a little more lately since it helps me with the shaking. My mom had the same issue when she was my age. The doctor took my vitals, and they were normal. I don't have any other medical issues. I underwent neurological exams and it showed that I’m shaky from both sides. The doctor diagnosed me with essential tremor.

Does the patient match the trial criteria? 1