Cerebellar Deep Brain Stimulation for Movement Disorders in Cerebral Palsy in Children and Young Adults

NCT06122675 | Recruiting DMC FDA Device

• 2 other identifiers: 22-37182UH3NS128297-01A1
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test the safety of placing Deep Brain Stimulators (DBS) in a part of the brain called the cerebellum and using electrical stimulation of that part of the brain to treat movement symptoms related to cerebral palsy. Ten children and young adults with dyskinetic cerebral palsy will be implanted with a Medtronic Percept Primary Cell Neurostimulator. We will pilot videotaped automated movement recognition techniques and formal gait analysis, as well as collect and characterize each subject's physiological and neuroimaging markers that may predict hyperkinetic pathological states and their response to therapeutic DBS.

Conditions

Dyskinetic Cerebral Palsy; Dystonic Cerebral Palsy

Outcome Measures

Primary Outcomes (2)

• Average total (global index) Movement Disorder-Childhood Rating Scale 4-18 Revised (MD-CRS 4-18-R) scores

  This is the primary motor outcome measure. It is the Movement Disorder-Childhood Rating Scale 4-18 Revised (MD-CRS 4-18 R). The MD-CRS 4-18 R is a validated tool aimed to evaluate movement disorders in developmental age. It is particularly useful for rating the severity of movement disorders in dyskinetic cerebral palsy. It scored based on two parts. Part I: General Assessment has a minimum total score of 0 (no impairment) and a maximum total score of 60 (maximal impairment). Part II: MD Assessment has a minimum total score of 0 (movement disorder is absent) and a maximum total score of 28 (maximal movement disorder presence).

  Evaluated weekly during randomized blinded phase (total of 3 months in each condition, sham stimulation and effective stimulation).

• Average total standardized Caregiver Priorities & Child Health Index of Life with Disabilities (CPCHILD) scores

  This is the primary Quality of Life (QOL) outcome measure. It is the Caregiver Priorities \& Child Health Index of Life with Disabilities (CPCHILD) scale. The CPCHILD is a reliable and valid measure of caregivers' perspectives on health status, functional limitations, and well-being of patients with severe CP, including those individuals who are non-verbal and non-ambulatory. Because many children suffering with CP are severely affected in many areas of their lives including activities of daily living, communication, mobility and overall health, there is an imperative to evaluate new interventions, especially invasive and resource-intensive ones such as DBS, using outcomes that are more meaningful to patients and their caregivers. Scores for each domain and for the total survey are standardized and range from 0 (worst) to 100 (best).

  Evaluated weekly during randomized blinded phase (total of 3 months in each condition, sham stimulation and effective stimulation).

Study Arms (2)

Effective stimulation

ACTIVE COMPARATOR

All participants will receive deep brain stimulation (DBS) in the cerebellum. For the first 20 weeks, every participant undergoes an open label phase to titrate stimulation and determine optimal stimulation settings. Following that phase, each participant starts three cycles of randomized, paired 8-week exposure periods, each pair including effective stimulation followed by sham stimulation, or vice versa. Effective stimulation will be the optimal stimulation settings determined during the open label phase.

Device: DBS

Sham stimulation

SHAM COMPARATOR

Sham stimulation will be settings at low amplitude (0.1mA) known to be ineffective.

Device: DBS

Interventions

DBS DEVICE

Implanted in the cerebellum.

Also known as: Medtronic Percept

Effective stimulation; Sham stimulation

Eligibility Criteria

• Age: 7 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis of DCP (dystonic and/or choreoathetotic cerebral palsy) with or without comorbid spasticity, with a clear history of hypoxic ischemic brain injury preceding motor symptoms made by a pediatric neurologist, with supporting MRI findings.
• Age 7-25 at the time of surgery.
• Gross Motor Function Classification System (GMFCS) Levels II-V.
• History of appropriate therapy with oral medications with inadequate relief as determined by a movement disorders or pediatric neurologist. Prior history of selective dorsal rhizotomy is allowed.
• Patient and family have requested surgical intervention with DBS for their movement disorder.
• No gross cerebellar abnormalities observed and reported on structural MRI.
• Written informed consent and written/verbal assent for those younger than 18 years of age.
• Ability to comply with study follow-up visits for brain recordings, neuroimaging and testing of sham and effective stimulation and clinical assessments.

You may not qualify if:

• Coagulopathy, uncontrolled epilepsy, severe cardiopulmonary or gastrointestinal conditions, or other medical conditions considered to place the patient at elevated risk for surgical complications.
• Pregnancy: all women of child-bearing potential will be required to have a negative urine pregnancy test prior to undergoing their surgical procedure.
• Severe fixed contractions and skeletal deformities that would preclude determination of improvement.
• Traumatic brain injury (i.e., non-accidental trauma) or history of infectious or autoimmune encephalitis.
• Requirement of diathermy, electroconvulsive therapy or transcranial magnetic stimulation.

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Institutes of Health (NIH): collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94158, United States

RECRUITING

Related Publications (2)

• San Luciano M, Oehrn CR, Wang SS, Tolmie JS, Wiltshire A, Graff RE, Zhu J, Starr PA. Protocol for combined N-of-1 trials to assess cerebellar neurostimulation for movement disorders in children and young adults with dyskinetic cerebral palsy. BMC Neurol. 2024 Apr 29;24(1):145. doi: 10.1186/s12883-024-03633-z.

  PMID: 38684956 DERIVED

• San Luciano M, Oehrn CR, Wang SS, Tolmie JS, Wiltshire A, Graff RE, Zhu J, Starr PA. Protocol for combined N-of-1 trials to assess cerebellar neurostimulation for movement disorders in children and young adults with dyskinetic cerebral palsy. Res Sq [Preprint]. 2024 Apr 1:rs.3.rs-4077387. doi: 10.21203/rs.3.rs-4077387/v1.

  PMID: 38645256 DERIVED

MeSH Terms

Conditions

Cerebral Palsy

Condition Hierarchy (Ancestors)

Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Marta San Luciano Palenzuela, MD, MS

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marta San Luciano Palenzuela, MD, MS

CONTACT

4153532311; Marta.SanLucianoPalenzuela@ucsf.edu

Sarah Wang, PhD, CCRP

CONTACT

4153537885; Sarah.Wang@ucsf.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Neurology

Model Details: The differences in primary outcome scores are calculated while on intervention (effective stimulation) versus placebo (sham stimulation), using an N-of-1 trial design. Each N-of-1 trial consists of a baseline assessment prior to DBS surgery (4 weeks), DBS surgery and open label phase to determine optimal stimulation settings (20 weeks), followed by a randomized three-cycle sequence of paired 8-week exposure periods, with each pair including intervention then placebo or vice versa (24 weeks). The DBS intervention exposure will be at the personalized optimal stimulation settings determined during the open-label phase.

Study Record Dates

• First Submitted: November 2, 2023
• First Posted: November 8, 2023
• Study Start: March 26, 2024
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): March 31, 2029
• Last Updated: March 27, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)