Clinical trial NCT05624385: MRgFUS Thalamotomy for Therapy-Resistant Tremor-related Disease With Low SDR Value
Official title: A Feasibility Study of MRgFUS in the Treatment of Therapy-Resistant Tremor-Related Patients With Low SDR Value
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Movement Disorders
Keywords: Essential tremor
Parkinson disease
MRgFUS
Lead sponsor: Chinese PLA General Hospital
Sponsor class: OTHER
First posted: 2022-11-22
Enrollment: 20
Sex: ALL
Minimum age (years): 22
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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).

Eligibility criteria: 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).

Primary outcomes:
measure: 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.
timeFrame: 2 years
Secondary outcomes:
measure: 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.
timeFrame: 2 years
measure: 2.2. Effectiveness
timeFrame: 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chinese PLA General Hospital
Study officials:
References: