Focused Ultrasound Pallidotomy for Dyskinetic Cerebral Palsy in Pediatric and Young Adult Subjects

Safety and Impact on Quality of Life of Focused Ultrasound Pallidotomy for Dyskinetic Cerebral Palsy in Pediatric and Young Adult Subjects

The primary objective of the proposed study is to evaluate the safety of ExAblate Transcranial MRgFUS as a tool for creating bilateral or unilateral lesions in the globus pallidus (GPi) in patients with treatment-refractory secondary dystonia due to dyskinetic cerebral palsy

Study Overview

• Status: Recruiting
• Conditions: Cerebral Palsy, Dyskinetic; Secondary Dystonia
• Intervention / Treatment: Device: Focused Ultrasound Pallidotomy

Detailed Description

The primary objective of the proposed study is to evaluate the safety of ExAblate Transcranial MRgFUS as a tool for creating bilateral or unilateral lesions in the globus pallidus (GPi) in patients with treatment-refractory secondary dystonia due to dyskinetic cerebral palsy.

The secondary is to assess the impact on Quality of Life of Focused Ultrasound Bilateral and unilateral Pallidotomy for Dyskinetic Cerebral Palsy in Pediatric and Young Adult Subjects. In addition, the impact of bilateral pallidotomy on motor development, pain perception, speech, memory, attention and cognition in these patients will also be assessed.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chima Oluigbo, MD; Phone Number: 2024763531; Email: coluigbo@childrensnational.org
• Study Contact Backup: Name: Saige Teti; Phone Number: 2024763755; Email: sateti@childrensnational.org

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Recruiting
      • Children's National Hospital
      • Contact: Chima Oluigbo, MD; Phone Number: 202-476-3531; Email: coluigbo@childrensnational.org
      • Contact: Saige Teti, BA; Phone Number: 2024763020; Email: sateti@childrensnational.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The treating physician has chosen GPi-DBS or pallidotomy for the treatment of the secondary dystonia caused by cerebral palsy in this patient
• Patient and/or legal representative, if the patient is underaged or not capable to give consent himself, have chosen pallidotomy as treatment
• The consent to participate in the trial of the underaged patient, if he is capable to understand the study requirements, is required
• Age at enrolment 8-22 years
• Diagnosis of secondary dystonia due to cerebral palsy caused by perinatal hypoxic injury
• Anti-dystonic pharmacotherapy insufficient
• Stable anti-dystonic medication over the last 30 days
• Globus pallidus internus (pars posterior) and thalamus (motor part) intact on MRI (not older than 2 years - if possible)
• No fixed severe skeletal deformations with loss of function, which need immediate orthopaedic surgical intervention
• Sufficient compliance of the patient or the legal representative if the patient is underaged or not capable to give consent himself to take part in the study
• Informed consent to take part in the study from patient and/or legal representative if the patient is underaged or not capable to give consent himself
• Patient and/or legal representative if the patient is underaged or not capable to give consent himself, understands the study requirements and the treatment procedures and provides written informed consent before any study-specific tests or procedures are performed

Exclusion Criteria:

• Patients with known primary (e.g. DYT1) or idiopathic dystonia
• Severe axial hypotonia with total loss of head control (e.g. absence of control at "upper thoracic level" in the SATCo score) (medication effect excluded)
• Fixed hemi-dystonia
• Severe spasticity in knee- and elbow-flexors and -extensors (Modified Ashworth Scale >3)
• Fixed severe skeletal contractions with loss of function which require immediate orthopaedic surgical intervention
• Patients with other severe concurrent neurological disease (e. g. brain tumor, neurodegenerative diseases, trauma etc.)
• Condition likely to require use of MRI in the future
• Any intracranial abnormality or medical condition that would contraindicate DBS surgery
• Any findings in neuropsychological screening assessments that would contraindicate DBS surgery
• Any current drug and / or alcohol abuse
• Any history of frequent grand-mal seizures without response to anticonvulsive treatment
• Any other active implanted device (e.g. Cochlear implant, pacemaker), whether turned on or off, would be allowed provided that they do not interfere with functioning of the device.
• The presence of DBS leads due the risks of these ferromagnetic devices in the MRI environment.
• A history of neurostimulation intolerance in any area of the body.
• Currently on any anticoagulant medications that cannot be discontinued during perioperative period.
• Any significant medical condition that is likely to interfere with study procedures or likely to confound evaluation of study endpoints, including any terminal illness with survival <24 months.
• Participation in another drug, device, or biologics trial concurrently or within the preceding 30 days; any other trial participation should be approved by the Principal Investigator.
• A female that is breastfeeding or of childbearing potential with a positive urine pregnancy test or - if a person is sexually active - not using sufficient contraception with a Pearl Index of less than 1% including all forms of hormonal contraception ("antibaby-pill", hormonal plaster, NuvaRing®, Implanon®, hormonal depot injections, contraceptive coil), the tubal ligature (female sterilization). Alternatively, the female of child bearing potential is sexually abstinent.
• Subjects who have contraindications to anesthesia, in the judgment of the attending anesthesiologist
• Subjects who are unwilling or unable to undergo general anesthesia
• Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the subject or the quality of the data.
• Minimum head circumference < 49cm
• Skull Density Ratio (SDR) <0.40.

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: Focused Ultrasound Pallidotomy; Pediatric and young adult patients between ages of 8 and 22 years with pharmaco-resistant secondary dystonia due to dyskinetic cerebral palsy who have Focused Ultrasound Pallidotomy	Device: Focused Ultrasound Pallidotomy; Use of ExAblate Transcranial MR guided Focused Ultrasound as a tool for creating bilateral or unilateral lesions in the globus pallidus (GPi) in patients with treatment-refractory secondary dystonia due to dyskinetic cerebral palsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of device-related and procedure-related adverse events (AE)	Safety will be determined by an evaluation of the incidence and severity of device-related and procedure-related adverse events (AE) from the first treatment day visit through the 24-month post-treatment time point. All AEs will be reported and categorized as related to the device versus the ablation procedure.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Burke-Fahn-Marsden-Dystonia Rating Scale movement and disability	Assessment of speech and swallowing. Score range: 0-30, 0 indicates complete independence, 30 indicates complete dependence.	2 years
Family Scale (FaBel)	Assessment of the burden for caregivers. Score range: 0-84, 0 indicates no burden, 84 indicates very severe burden.	2 years
Canadian Occupational Performance Measure (COPM)	Assessment of activities of daily living.	2 years
Gross Motor Function Measure (GMFM-66)	Assessment of physical disability. Score range: 0-3, 0 indicates no performance, 3 indicates complete performance.	2 years
Gross Motor Function Classification System (GMFCS)	Degree of physical impairment. Score range: 1-5, 1 indicates no limitations, 5 indicates severe limitations.	2 years
SF-36 for assessment of quality of life	Assessment of quality of life of subject. Score range: 0-100, 0 indicates bad health state, 100 indicates an excellent health state.	2 years
Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD)	Assessment of Quality of life of Caregivers and Subject. Score range: 0-100, 0 indicates a bad score, 100 indicates an excellent score.	2 years
Frenchay Dysarthria Assessment	Assessment of speech and swallowing. Score range:	2 years
Assessment of Cognition	Snijders-Oomen-Non-Verbal-Intelligence Test (SON-R)	2 years
Strengths and Difficulties Questionnaire	Assessment of mood and attention. Score range: 0-40, 0 indicates normal, 40 indicates abnormal.	2 years
Assessment of Attention	Attentional Network Test (ANT)	2 years
Assessment of cognition	Non-Verbal-Learning Test (NVLT)	2 years
Wong Baker Faces	Assessment of pain. Score range; 0-10, 0 indicates no pain, 10 indicates worst pain.	2 years
Tardieu Scale	Assessment of the severity of spasticity. Score range: 0-5, 0 indicates no resistance, 5 indicates no movement.	2 years
Dyskinesia Impairment Scale (DIS)	Assessment of the severity of chorea and dystonia. Score range: 0-576, 0 indicates no dystonia, 576 indicates very severe dystonia.	2 years
Barry Albright Dystonia Scale	Score range: 0-32, 0 indicates no dystonia, 32 indicates severe dystonia.	2 years

Collaborators and Investigators

• Sponsor: Children's National Research Institute
• Investigators: Principal Investigator: Chima Oluigbo, MD, Children's National Hospital, Washington, DC

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2024
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: May 2, 2023
• First Submitted That Met QC Criteria: September 12, 2023
• First Posted (Actual): September 13, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 10, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Pallidotomy; High intensity focused ultrasound (HIFU)
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Brain Damage, Chronic; Dyskinesias; Cerebral Palsy; Dystonia; Dystonic Disorders
• Other Study ID Numbers: G230044

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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