Deep Brain Stimulation for Cerebral Palsy

Overseen By Sarah Wang, PhD, CCRP

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Francisco

Disqualifiers: Uncontrolled epilepsy, Severe cardiopulmonary, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment method called Deep Brain Stimulation (DBS) to manage movement issues in children and young adults with cerebral palsy. DBS involves placing a device in the brain to send electrical signals to the cerebellum, aiming to improve movement symptoms. Participants must have a specific type of cerebral palsy with a history of brain injury and have found little relief from medication. The trial will test different stimulation settings to identify the most effective one for each participant. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research and potentially benefit from a novel treatment approach.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should have a history of trying oral medications without adequate relief, so it's possible you may need to continue them.

What prior data suggests that this device is safe for treating movement symptoms related to cerebral palsy?

Research has shown that cerebellar deep brain stimulation (DBS) is generally safe for individuals with cerebral palsy. In studies involving patients with dystonic and spastic cerebral palsy, participants tolerated the treatment well. These studies included children and young adults, similar to those who might join the current trial. One study found that DBS significantly improved muscle stiffness in both arms and legs, suggesting it could help with movement issues.

No major safety concerns emerged in these studies, indicating the treatment is relatively safe, though individual reactions may vary. Prospective trial participants should discuss any concerns with a healthcare professional. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about cerebellar deep brain stimulation (DBS) for cerebral palsy because it offers a novel approach by directly targeting the brain's motor control regions. Unlike traditional therapies, such as physical therapy and muscle relaxants that primarily manage symptoms, DBS aims to enhance motor function by electrically stimulating the cerebellum. This innovative method could potentially improve movement and coordination more effectively and sustainably. Additionally, the ability to fine-tune stimulation settings for each individual means that treatment can be highly personalized, increasing the chances of meaningful improvements in quality of life for those with cerebral palsy.

What evidence suggests that Cerebellar Deep Brain Stimulation is effective for treating movement symptoms in cerebral palsy?

Research has shown that deep brain stimulation (DBS) can improve movement in individuals with movement disorders. In earlier studies, patients with cerebral palsy demonstrated better hand movements, coordination, walking, head control, and speech after receiving DBS. This trial will administer cerebellar DBS to all participants, targeting the cerebellum, which typically remains undamaged in cerebral palsy, making it a promising focus area. DBS has successfully treated other movement disorders by using electrical signals to control movement. This success suggests that DBS could also help manage movement symptoms in individuals with cerebral palsy. ^{1 2 4 5 6}

Who Is on the Research Team?

Marta San Luciano Palenzuela

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 7-25 with dyskinetic cerebral palsy (DCP), who have tried oral medications without enough relief. They should be able to attend follow-up visits, have a history of brain injury before their motor symptoms started, and not have major cerebellar abnormalities on an MRI.

Inclusion Criteria

No gross cerebellar abnormalities observed and reported on structural MRI

My family and I have chosen surgery with DBS for my movement disorder.

My mobility is moderately to severely limited.

Exclusion Criteria

Pregnancy: all women of child-bearing potential will be required to have a negative urine pregnancy test prior to undergoing their surgical procedure

I have severe joint stiffness or bone deformities that would not show improvement.

I need treatments like diathermy, electroconvulsive therapy, or magnetic stimulation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Open-label Phase

Participants undergo an open label phase to titrate stimulation and determine optimal stimulation settings

20 weeks

Randomized Blinded Phase

Participants start three cycles of randomized, paired 8-week exposure periods, each pair including effective stimulation followed by sham stimulation, or vice versa

24 weeks

Weekly evaluations

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cerebellar Deep Brain Stimulation

Trial Overview The study tests the safety of Deep Brain Stimulation (DBS) in the cerebellum using Medtronic Percept Neurostimulators to treat movement disorders caused by cerebral palsy. It includes videotaped movement analysis, gait analysis, and monitoring physiological and neuroimaging markers.

How Is the Trial Designed?

Group I: Effective stimulation Active Control 1 Intervention

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.

Group II: Sham stimulation Placebo Group 1 Intervention

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

Cerebellar Deep Brain Stimulation is already approved in United States for the following indications:

Approved in United States as Cerebellar Deep Brain Stimulation for:

• Dyskinetic cerebral palsy
• Movement disorders in cerebral palsy

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

Dyskinetic cerebral palsy (DCP) presents significant treatment challenges due to its complex motor symptoms, including chorea, athetosis, and dystonia, which are often not effectively managed with pharmacological options.

Deep brain stimulation (DBS) targeting the basal ganglia or cerebellum shows promise as a therapeutic approach for selected patients with DCP, based on a review of the largest available studies on this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for dystonia due to cerebral palsy: A review. Elia, AE., Bagella, CF., Ferré, F., et al.[2018]

Bilateral deep brain stimulation (DBS) targeting the dentate nucleus in three patients with dyskinetic cerebral palsy (DCP) was found to be safe and resulted in subjective and objective improvements in motor function, as measured by the Burke-Fahn-Marsden Dystonia Rating Scale.

The study suggests that the cerebellum may be a promising target for DBS in DCP patients, as it is often spared from hypoxic ischemic damage, but further research with larger sample sizes and long-term follow-up is needed to confirm these preliminary findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebellar deep brain stimulation for the treatment of movement disorders in cerebral palsy. Cajigas, I., Morrison, MA., Luciano, MS., et al.[2023]

Deep brain stimulation of the dentate nucleus (DN DBS) is a safe and well-tolerated procedure for patients with cerebellar symptoms, showing no serious adverse events in a pilot trial with five participants.

While DN DBS did not achieve statistical significance in improving overall ataxia scores, it did lead to significant improvements in tremor severity and patients' global impression of change, indicating potential benefits in specific symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Outcomes of Dentate Nucleus Deep Brain Stimulation for Cerebellar Ataxia. Cury, RG., França, C., Duarte, KP., et al.[2022]

Bilateral cerebellar stimulation was successfully implanted in 2 children with cerebral palsy, leading to a significant reduction in spasticity and improvement in fine motor control over an 8-month follow-up period.

These preliminary results support the potential of cerebellar stimulation as a clinical treatment for sensory-motor disorders in children with cerebral palsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The influence of permanent cerebellar stimulation on senso-motor disorders in cerebral palsy (author's transl)]. Winkelmüller, W., Seidel, BU., Dietz, H.[2006]

In a study of 68 cerebral palsy patients who underwent deep cerebellar stimulation, characteristic responses included immediate motor jerks followed by relaxation and feelings of pleasure, indicating potential therapeutic effects of targeted electrical stimulation.

The effectiveness of stimulation depended on the current level; too high a current could worsen symptoms, while too low had no effect, highlighting the importance of individualized adjustments for optimal outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Motor and psychological responses to deep cerebellar stimulation in cerebral palsy (correlation with organization of cerebellum into zones). Galanda, M., Zoltán, O.[2019]

Deep cerebellar stimulation significantly reduced muscle tone and improved psychomotor status in 11 out of 13 patients with cerebral palsy over a 2-year follow-up, with notable improvements in walking and speech for some individuals.

The procedure is considered safe and effective, being non-ablative and reversible, although there were some complications, including infections in 23.1% of cases, which led to the removal of stimulators in two patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical evaluation of deep cerebellar stimulation for spasticity in patients with cerebral palsy. Harat, M., Radziszewski, K., Rudaś, M., et al.[2016]

Deep brain stimulation (DBS) significantly improved dyskinesia in pediatric patients with dyskinetic cerebral palsy (DCP) over a follow-up period of 36 months, as measured by the Dyskinesia Impairment Scale.

Despite the improvement in dyskinesia, other motor and non-motor outcomes did not show significant changes, and there were 12 serious adverse events possibly related to the treatment, highlighting the need for further research with larger patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Follow-Up of Pediatric Patients with Dyskinetic Cerebral Palsy and Deep Brain Stimulation. Koy, A., Kühn, AA., Schiller, P., et al.[2023]

Chronic cerebellar stimulation in 50 patients with cerebral palsy led to significant improvements in symptoms such as spasticity, athetosis, speech, and overall functional status, with continued improvement noted over time.

The procedure was generally safe, with no neurological complications reported, although there was one death in the series, suggesting that while effective, careful consideration is needed when using this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic cerebellar stimulation in cerebral palsy. Cooper, IS., Riklan, M., Amin, I., et al.[2019]

The study analyzed the placement of stimulating electrodes in the deep regions of the cerebellum, revealing a correlation between electrode position and the resulting motor responses, which ranged from bilateral to ipsilateral effects.

Combining deep cerebellar stimulation with a destructive method in the supratentorial region may provide an effective treatment strategy for reducing spasticity and enhancing motor function in certain cases of cerebral palsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Behavioural responses to cerebellar stimulation in cerebral palsy. Galanda, M., Mistina, L., Zoltan, O.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10691838/

Cerebellar Deep Brain Stimulation in Cerebral Palsy Patients experienced subjective improvement in motor function including ease of hand movements and coordination, gait, head control, speech, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06122675

Cerebellar Deep Brain Stimulation for Movement Disorders ... 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 ...

3. thejns.org thejns.org/view/journals/j-neurosurg/139/3/article-p605.xml

Cerebellar deep brain stimulation for the treatment of ... The cerebellum has been posited as an attractive target for treatment of DCP because it is frequently spared from hypoxic ischemic damage.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0969996122002911

Cerebellar deep brain stimulation for movement disorders Deep brain stimulation (DBS) targeting at cerebellum can be an effective tool to treat these movement disorders.

5. bmcneurol.biomedcentral.com bmcneurol.biomedcentral.com/articles/10.1186/s12883-024-03633-z

Protocol for combined N-of-1 trials to assess cerebellar ... DBS in traditional targets (globus pallidus and motor thalamus) can improve motor, disability and pain ratings in DCP, but motor and quality of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10726727/

Cerebellar deep brain stimulation for the treatment of ... In 10 patients with dystonic and spastic CP, anterior cerebellar high-frequency DBS significantly improved upper- and lower-limb spasticity and ...