Clinical trial NCT06974916: EMBRACE Tremor BiFUS
Official title: European, Multicenter, Investigator Blinded, Randomized And Controlled Essential Tremor Trial With Staged-Bilateral FUS
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Essential Tremor
Lead sponsor: InSightec
Sponsor class: INDUSTRY
First posted: 2025-05-16
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a post-market (Phase IV) randomized, controlled, blinded, multicenter study with the aim to determine the added value of staged bilateral Exablate thalamotomy compared to a group of patients on previous unilateral treatment combined with local standard medical treatment.

Detailed description: In patients who have undergone previous unilateral Exablate thalamotomy for Essential Tremor, the aim of this trial is to determine the effect of staged bilateral Exablate thalamotomy compared to a group of patients on previous unilateral treatment. The effect will be measured on tremor reduction, functional impairment, disease-specific quality of life, adverse events and patient-perception of the overall treatment result in patients eligible for a staged bilateral Exablate procedure.

Patients assigned to the treatment arm will receive staged bilateral Exablate thalamotomy. Patients assigned to control group will remain under local standard medical treatment.

The primary efficacy study objective is to demonstrate that Exablate staged-bilateral thalamotomy treatment reduces tremor, as measured by Treated Upper Limb CRST (A+B) (0-28) score, to a higher extent than those remaining on previous unilateral Exablate thalamotomy at 6 months.

The primary safety study objective is to assess the adverse events (AEs) of Exablate staged-bilateral thalamotomy treatment in comparison to those remaining on unilateral treatment (control group) plus medical treatment, including AE type, incidence, severity and duration at 6 months.

Eligibility criteria: Inclusion Criteria:

1. Men and women with an age of 18 years or older.
2. Willing to participate in the study (i.e., signed ICF). (Willing to be randomized).
3. Patient is able to undergo a high-resolution Computerized Tomography (CT) scan.
4. Patient is able to fit into MRI unit and comply with all contraindications for the specific magnetic resonance (MR) system including and limited to contrast medium should there be needed.
5. The thalamus, sub-thalamus and the pallidum must be apparent on MR imaging.
6. Patient is able to communicate sensations to the physician during the procedure; Procedure does not require general anesthesia.
7. Patient must be able to use the Stop Sonication button freely.
8. Patient willing to have their head shaved prior to the actual treatment.
9. Patient has no history for claustrophobia which is not responding to medications.
10. ET patients who are eligible for second side staged bilateral Exablate thalamotomy treatment. Time since first intervention is at least 9 months.
11. Available tremor assessment prior to the unilateral Exablate thalamotomy.
12. Patients randomized to the study, irrespective of group allocation should be willing and able to remain in the study for at least 6 months and able to complete the required assessments.

Exclusion Criteria:

1. Subject experienced any non-transient neurological event or worsening following the previous Exablate procedure.
2. Patients with MRI related contraindications (e.g. presence of metallic implants incompatibility with MRI, severe claustrophobia, reaction to contrast medium).
3. Patients in whom it is not possible to avoid energy absorbing structures or sensitive tissues (e.g., skull implants, surgical clips, shunts, electrodes, dura patch, skull patch, electrodes, etc.) from the path of the ultrasound beam.
4. Patients with concurrent active infections disease and/or severe allergies with fever.
5. Patients that have been diagnosed with brain tumors or a vascular anomaly.
6. Patients with a history of seizures, brain hemorrhages, stroke within the past year, or any coagulopathy.
7. Patients under anticoagulants and/or anti-platelets drugs known to increase bleeding risk within the duration defined by the half-life of the specific drugs.
8. Patient that has been given any contrast agent (e.g., CT, MRI), within 24 hours before treatment
9. Severe unstable hypertension that cannot be controlled by medications (diastolic Blood Pressure \> 100 on medication).
10. Patients with unstable cardiac status.
11. Patients exhibiting any behavior(s) consistent with ethanol or substance abuse.
12. Cerebrovascular disease (multiple CVA or CVA within 6 months).
13. Patients with risk factors for intraoperative or postoperative bleeding.
14. Imaging shows abnormal finding in CT or/and MRI (e.g., brain tumor, brain vascular malformation, shunt, etc.).
15. Patient has physical subscale score ≥ 16.5 on the Dysphagia Handicap Index or has been diagnosed with dysphagia.
16. Patient with cognitive impairment.
17. Patient with clinically significant abnormal speech function as determined by a speech pathologist.

Primary outcomes:
measure: Treated Upper Limb Clinical Rating Scale for Tremor (CRST) (A+B) (0-28) score for the treated side.
timeFrame: 6 Months
Secondary outcomes:
measure: Treated Upper Limb Clinical Rating Scale for Tremor (CRST) (A+B) (0-28) score as assessed by the blinded reviewers of the video-recordings.
timeFrame: 6 Months, 12 Months
measure: Clinical Rating Scale for Tremor (CRST) part A (0-76)
timeFrame: 6 Months, 12 Months
measure: Bilateral Upper Limb Clinical Rating Scale for Tremor (CRST) (A+B) (0-56)
timeFrame: 6 Months, 12 Months
measure: Total Clinical Rating Scale for Tremor (CRST) (A+B) (0-116)
timeFrame: 6 Months, 12 Months
measure: Clinical Rating Scale for Tremor (CRST) part C (0-32)
timeFrame: 6 Months, 12 Months
measure: Axial Clinical Rating Scale for Tremor (CRST) (0-20)
timeFrame: 6 Months, 12 Months
measure: Quality of life questionnaire
timeFrame: 6 Months, 12 Months
measure: Change of tremor medication
timeFrame: 6 Months, 12 Months
measure: Safety: Incidence and frequency of adverse events related to the treatment.
timeFrame: 6 Months, 12 Months
Other outcomes:
measure: Objective assessment of specific adverse events
timeFrame: 6 Months, 12 Months
measure: Patient Global Impression of Change (PGIC)
timeFrame: 6 Months, 12 Months
measure: Clinician Global Impression of Change (CGIC)
timeFrame: 6 Months, 12 Months
measure: Caregiver Global Impression of Change (CaGIC)
timeFrame: 6 Months, 12 Months
measure: Responder analysis
timeFrame: 6 Months
Locations:
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein, Campus Kiel (UKSH)
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Neurologico Carlo Besta
city: Móstoles
country: Spain
facility: HM CINAC- Hospital Universitario HM Puerta del Sur
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
Study officials:
affiliation: Universitätsklinikum Schleswig-Holstein, Campus Kiel (UKSH)
name: Günther Deuschl
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitätsklinikum Schleswig-Holstein, Campus Kiel (UKSH)
name: Steffen Paschen
role: PRINCIPAL_INVESTIGATOR
References: