EMBRACE Tremor BiFUS

Official title

International, Multicenter, Investigator Blinded, Randomized And Controlled Essential Tremor Trial With Staged-Bilateral FUS

Overview

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.

Interventions

• Procedure Staged bilateral Exablate thalamotomy
  Staged bilateral Exablate thalamotomy in ET patients
• Other Local standard medical treatment after previous Exablate unilateral thalamotomy.
  Local standard medical treatment

Primary outcome measures

• Treated Upper Limb Clinical Rating Scale for Tremor (CRST) (A+B) (0-28) score for the treated side. [Time frame: 6 Months]

Secondary outcome measures (9)

• Treated Upper Limb Clinical Rating Scale for Tremor (CRST) (A+B) (0-28) score as assessed by the blinded reviewers of the video-recordings. [Time frame: 6 Months, 12 Months]
• Clinical Rating Scale for Tremor (CRST) part A (0-76) [Time frame: 6 Months, 12 Months]
• Bilateral Upper Limb Clinical Rating Scale for Tremor (CRST) (A+B) (0-56) [Time frame: 6 Months, 12 Months]
• Total Clinical Rating Scale for Tremor (CRST) (A+B) (0-116) [Time frame: 6 Months, 12 Months]
• Clinical Rating Scale for Tremor (CRST) part C (0-32) [Time frame: 6 Months, 12 Months]
• Axial Clinical Rating Scale for Tremor (CRST) (0-20) [Time frame: 6 Months, 12 Months]
• Quality of life questionnaire [Time frame: 6 Months, 12 Months]
• Change of tremor medication [Time frame: 6 Months, 12 Months]
• Safety: Incidence and frequency of adverse events related to the treatment. [Time frame: 6 Months, 12 Months]

Eligibility criteria

Inclusion criteria

• Men and women with an age of 18 years or older (according to local labeling).
• Willing to participate in the study (i.e., signed ICF). (Willing to be randomized).
• Patient is able to undergo a high-resolution Computerized Tomography (CT) scan.
• 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.
• The thalamus, sub-thalamus and the pallidum must be apparent on MR imaging.
• Patient is able to communicate sensations to the physician during the procedure; Procedure does not require general anesthesia.
• Patient must be able to use the Stop Sonication button freely.
• Patient willing to have their head shaved prior to the actual treatment.
• Patient has no history for claustrophobia which is not responding to medications.
• ET patients who are eligible for second side staged bilateral Exablate thalamotomy treatment (according to local labeling). Time since first intervention is at least 9 months.
• Available tremor assessment prior to the unilateral Exablate thalamotomy.
• 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

• Subject experienced any non-transient neurological event or worsening following the previous Exablate procedure.
• Patients with MRI related contraindications (e.g. presence of metallic implants incompatibility with MRI, severe claustrophobia, reaction to contrast medium).
• 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.
• Patients with concurrent active infections disease and/or severe allergies with fever.
• Patients that have been diagnosed with brain tumors or a vascular anomaly.
• Patients with a history of seizures, brain hemorrhages, stroke within the past year, or any coagulopathy.
• 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.
• Patient that has been given any contrast agent (e.g., CT, MRI), within 24 hours before treatment
• Severe unstable hypertension that cannot be controlled by medications (diastolic Blood Pressure > 100 on medication).
• Patients with unstable cardiac status.
• Patients exhibiting any behavior(s) consistent with ethanol or substance abuse.
• Cerebrovascular disease (multiple CVA or CVA within 6 months).
• Patients with risk factors for intraoperative or postoperative bleeding.
• Imaging shows abnormal finding in CT or/and MRI (e.g., brain tumor, brain vascular malformation, shunt, etc.).
• Patient has physical subscale score ≥ 16.5 on the Dysphagia Handicap Index or has been diagnosed with dysphagia.
• Patient with cognitive impairment.
• Patient with clinically significant abnormal speech function as determined by a speech pathologist.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Spain · 4 centers

• Germans Trias i Pujol Hospital — Badalona
• HM CINAC- Hospital Universitario HM Puerta del Sur — Móstoles
• Clinica Universidad de Navarra — Pamplona
• Ascires Hospital_ECG Salud — Valencia

Japan · 3 centers

• Central Japan International Medical Center — Minokamo
• Kashiwaba Neurology Hospital — Sapporo
• Medical Research Institute KITANO HOSPITAL, PIIF Tazuke-Kofukai — Kita-ku

Taiwan · 2 centers

• Chang Bing Show Chwan Memorial Hospital — Changhua
• National Taiwan University Hospital — Taipei

Finland · 1 center

• Turku University Hospital — Turku

Germany · 1 center

• Universitätsklinikum Schleswig-Holstein, Campus Kiel (UKSH) — Kiel

Italy · 1 center

• Fondazione IRCCS Istituto Neurologico Carlo Besta — Milan

United Kingdom · 1 center

• The Walton Center — Liverpool

Identifiers

NCT: NCT06974916 · ET006

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗