Pilot study of safety and efficacy of unilateral MRI-guided focused ultrasound thalamotomy in tremor-dominant Parkinson’s disease

Not Applicable

• Conditions: Parkinson's disease; Nervous System Diseases

• Registration Number: ISRCTN17281700
• Lead Sponsor: niversity of Dundee

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2023-05-10
• Last Update Posted: 25 March 2024
• Study Completion: 2025-11-03

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

1. Men and women age 30 years or older.
2. Subjects who are able and willing to give consent and are able to attend all study visits.
3. An established diagnosis of Parkinson’s Disease as confirmed from clinical history based upon UK Brain Bank criteria.
4. Tremor refractory to adequate trials of at least two medications, including levodopa equivalent dosage of 800 mg (total daily dose). 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.
5. Tremor dominant PD defined by the UPDRS tremor scores (items 16,20,21) to the mean UPDRS postural instability/gait disorder scores (items 13-15,29,30) was = 1.5
6. Vim nucleus of the thalamus can be targeted by the MRgFUS device. The thalamic region must be apparent on MRI such that targeting can be performed by measurement from a line connecting the anterior and posterior commissures of the brain.
7. Able to communicate sensations during the treatment.
8. Postural or resting tremor severity score of grade 3 or 4 in the most affected hand/arm as measured by the CRST (part A) rating scale while stable on medication (items 1-9).
9. Significant disability due to Parkinson’s tremor despite medical treatment (CRST score of 2 or above in any one of the items 16-23 from the Disability subsection of the CRST: [speaking, feeding other than liquids, bringing liquids to mouth, hygiene, dressing, writing, working, and social activities])

Exclusion Criteria

1. Subjects with unstable cardiac status including:
1.1. Unstable angina pectoris on medication
1.2. Subjects with documented myocardial infarction within six months of protocol entry
1.3. Significant congestive heart failure
1.4. Subjects with unstable ventricular arrhythmias
1.5. Subjects with atrial arrhythmias that are not rate-controlled
2. Severe hypertension (diastolic BP > 100 on medication)
3. Significant speech impairment that would prevent communication during the procedure.
4. Unsteadiness when walking or turning and or instability on tandem walking during the formal examination.
5. Subjects with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations, etc.
6. Known intolerance or allergies to the MRI contrast agent (e.g. Gadolinium).
7. Patient with severely impaired renal function with estimated glomerular filtration rate <30 mL/min/1.73m2 (or per local standards should that be more restrictive) and/or who is on dialysis.
8. History of abnormal bleeding and/or coagulopathy
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 haemorrhage (e.g. Avastin) within one month of focused ultrasound procedure
10. History of immunocompromise including those who are HIV positive.
11. History of intracranial haemorrhage
12. Cerebrovascular disease (multiple CVA or CVA within 6 months)
13. Subjects with uncontrolled symptoms and signs of increased intracranial pressure (e.g., headache, nausea, vomiting, lethargy, papilledema).
14. Individuals who are not able or willing to tolerate the required prolonged stationary supine position during treatment (can be up to 4 hrs of total table time.)
15. Significant claustrophobia that cannot be managed with mild medication.
16. Subjects are unable to communicate with the investigator and staff.
17. Presence of any other neurodegenerative disease such as Parkinson-plus syndromes suspected on neurological examination. These include multisystem atrophy, progressive supranuclear palsy, dementia with Lewy bodies, and Alzheimer’s disease.
18. Presence of significant cognitive impairment as determined with a score = 85 on the ACE-R.
19. Diagnosis of Dementia including Parkinson’s Disease Dementia (PDD).
20. Subjects with life-threatening systemic diseases that include and are not limited to the following will be excluded from the study participation: HIV, Liver Failure, blood dyscrasias, etc.
21. Subjects with a history of seizures within the past year.
22. Subjects with a history of psychosis will be excluded. Subjects with a history of self-harm/personality disorder, bipolar disorder, or moderately severe depressive illness will be excluded. For the purpose of this study, we consider moderately severe depressive illness to include any subject who:
22.1. has an IDS-SR score > 26
22.2. is currently under the care of a psychiatrist
23. Subjects with risk factors for intraoperative or postoperative bleeding: platelet count less than 100,000 per cubic millimetre, INR coagulation studies exceeding local institution laboratory standards, or a documented coagulopathy
24. Subjects with brain tumours
25. Any illness that in the investigator's opinion precludes participation in this study.
26. Pregnancy or lactation.
27. Legal incapacity or limited legal capacity.
28. Subjects who have had deep brain stimulation o

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Tremor measured using the Clinical Rating Scale for Tremor (CRST) during MRgFUS treatment

Secondary Outcome Measures

Name	Time	Method
The following Secondary outcome measures are assessed on Day 1 and 6 months post-treatment:<br>1. Tremor measured using the Clinical Rating Scale for Tremor (CRST) <br>2. Symptoms associated with Parkinson’s disease measured using the Unified Parkinson's Disease Rating Scale (UPDRS)<br>3. Quality of life measured using the Parkinson's Disease Questionnaire (PDQ-39)<br>4. Adverse events will be recorded based on reported incidents in the participant’s medical notes at Visit 3 (24 hours after procedure) and Visit 4 (6 months after procedure)<br>5. Medication collection, and changes to medication, will be recorded in the patients medical notes at Visits 3 and 4.