MRgFUS Thalamotomy for Therapy-Resistant Tremor-related Disease With Low SDR Value

A Feasibility Study of MRgFUS in the Treatment of Therapy-Resistant Tremor-Related Patients With Low SDR Value

A study to evaluate the effectiveness and safety of ExAblate transcranial MRgFUS Thalamotomy treatment of medication refractory tremor-related diseases subjects with low skull density ratio (SDR) value.

Essential tremor (ET) and Parkinson disease (PD) are the most prevalent tremor disorders. ET, considered as a pure tremor disease, is characterized by upper limb intention or postural tremor, while PD is characterized by a variety of motor and non-motor symptoms, among them rest tremor. A number of studies have demonstrated that Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is a minimally invasive and effective procedure suitable for medication-refractory tremor in patients with ET and patients with PD. However, the skull is the main barrier to MRgFUS thalamotomy therapy and patients are screened by calculating SDR value before treatment. The US FDA recommended SDR value >0.45±0.05 as the inclusion criterion for screening patients with tremor treated by MRgFUS system. However, about 20%-50% of patients with SDR value are lower than this standard, which makes this part of patients excluded and unable to accept this treatment with many advantages such as non-invasive, no need for general anesthesia, and no need for hardware implantation. Therefore, this study intended to evaluate the safety and effectiveness of MRgFUS thalamotomy in the treatment of tremor-related patients with low SDR value, so as to provide clinical basis for more patients with tremor to benefit from this treatment.

Study Overview

• Status: Recruiting
• Conditions: Movement Disorders
• Intervention / Treatment: Device: MRgFUS treatment

Detailed Description

Patients:

Patients with medication-refractory ET and PD were included. Baseline materials, clinical rating scale for tremor (CRST) , treatment parameters(energy, power, duration time, temperature, target location) , associated adverse effects were recorded.

Imaging protocols:

T2; T2 Flair; DWI; ESWAN; MRS; 3D ASL 2.0s; 3D-T1; DTI; rs-functional MRI Imaging evaluation:

1. Lesion appearance and volume are measured by T2, T2 Flair, DWI, ESWAN, 3D-T1;
2. ESWAN and MRS manifests the changes of iron deposition and metabolism #respectively;
3. ASL shows regional cerebral blood flow associated with the procedure;
4. DTI demonstrates the destruction of white matter integrity.
5. Rs-functional MRI reflects alterations of resting-state brain activity.

Treatment:

MRgFUS thalamotomy

Follow-up:

Baseline (MRI+clinical evaluation); 1-day, 1-month, 3-months, 6-months,1-year, 2-years (MRI+clinical evaluation).

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yongqin Xiong, MD; Phone Number: +86 18518518771; Email: xiongyongqin118@163.com
• Study Contact Backup: Name: Xin Lou, MD,PhD; Phone Number: +86 18518518771

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Chinese PLA General Hospital
    • Contact: Xin Lou, MD/PhD
    • Contact: Yongqin Xiong, MD; Phone Number: +86 18518518771; Email: xiongyongqin118@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Men and women age 22 years or older;
2. Subjects are able and willing to agree to participate in the study and can accept all research visits;
3. A diagnosis of ET and PD as confirmed from clinical history and examination by a neurologist or neurosurgeon specialized in movement disorder and intolerance to side effects of medication or poor response to medication, severe and disabling tremor;
4. Able to adapt to MRI system;
5. To tolerate operation with or without some form of sedative (e.g., awake sedation);
6. Able to communicate with the doctor during the operation;
7. Able to use the "Stop ultrasonic processing" button;
8. Skull density ratio (SDR) ≥ 0.28.

Exclusion Criteria:

1. Subjects with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations, known intolerance or allergies to the MRI contrast agent (e.g.Gadolinium or Magnevist) including advanced kidney disease, etc;
2. Pregnant woman;
3. Subjects with severely impaired renal function;
4. Subjects with unstable cardiac status or severe hypertension (diastolic BP > 100 on medication);
5. Subjects show behaviors consistent with alcohol or drug abuse;
6. History of abnormal bleeding and/or coagulopathy/ or intracranial hemorrhage;
7. Patients who received anticoagulant therapy or medications known to increase the risk of bleeding within the month prior to receiving focused ultrasound treatment;
8. Cerebrovascular disease (multiple CVA or CVA within 3 months);
9. Subjects with brain tumors.
10. Individuals who are not able or willing to tolerate the required prolonged stationary position during treatment (can be up to 2 hrs of total time).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MRgFUS treatment	Device: MRgFUS treatment; ExAblate Transcranial MRgFUS Thalamotomy Treatment of Medication Refractory Tremor-Related Subjects; Other Names: Thalamotomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1.1 Safety To evaluate the incidence and severity of adverse events (AE/AEs) associated with ExAblate Transcranial MRgFUS treatment of subjects during 2-year follow-up.	All AE reported by the investigator are classified as: definitely relevant, very likely relevant, probably relevant, probably not relevant or definitely not relevant to the product under study, where definitely relevant, very likely relevant, possibly relevant are classified as relevant, probably not relevant and definitely not relevant are classified as irrelevant.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2.1. Safety To evaluate the incidence and severity of adverse events (AE/AEs) after ExAblate Transcranial MRgFUS treatment of subjects at 24 hours, 1 month, 3 months, 6 months, 12 months, and 2 years follow-up.	To evaluate the incidence of unexpected adverse device events (UADE) within 2 years after the treatment of the study product.	2 years
2.2. Effectiveness	The effectiveness will be evaluated by the hand tremor subscore (on a scale ranging from 0 to 32 when the dominant hand is treated and 0 to 28 points when the nondominant hand is treated, with higher scores indicating more severe tremor), which was derived from the Clinical Rating Scale for Tremor (CRST) . Both the treatment side and the non-treatment side of the subject will be evaluated. Clinical evaluation will be conducted at the following time points: at screening, at baseline, and 1, 3, 6, 12 months, and 2 years after treatment.	2 years

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2023
• Primary Completion (Anticipated): December 1, 2024
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: November 10, 2022
• First Submitted That Met QC Criteria: November 17, 2022
• First Posted (Actual): November 22, 2022

Study Record Updates

• Last Update Posted (Actual): April 4, 2023
• Last Update Submitted That Met QC Criteria: April 3, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Parkinson disease; Essential tremor; MRgFUS
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Movement Disorders; Tremor
• Other Study ID Numbers: MRgFUS-Tremor Disorders

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No