Movement Task Facilitation for Parkinson's Disease

Overseen By Mai Miura, BA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, Los Angeles

Must not be taking: Anticoagulants, Antiplatelets

Disqualifiers: Cognitive disease, Psychiatric disease, 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: 1

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Several strategies or contexts help patients with Parkinson's disease to move more quickly or normally, however the brain mechanisms underlying these phenomena are poorly understood. The proposed studies use intraoperative recordings during DBS surgery for Parkinson's disease to understand the brain mechanisms supporting improved movements elicited by external cues. The central hypothesis is that distinct networks are involved in movement improvement depending on characteristics of the facilitating stimulus. Participants will perform movement tasks during awake surgery performed exclusively for clinical indications. The identified biomarkers may provide targets for future neuromodulation therapies to improve symptoms that are refractory to current treatments, such as freezing of gait.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that anticoagulant or antiplatelet therapy should not be used within 1 week before surgery.

Is deep brain stimulation (DBS) generally safe for humans?

Deep brain stimulation (DBS) is generally considered safe for humans, but it can have complications like infections, lead migrations, and device malfunctions. These issues sometimes require additional surgery to fix. Despite these risks, many experts believe the benefits of DBS outweigh the risks for treating movement disorders like Parkinson's disease. ^{1 2 3 4 5}

How does the treatment Movement task (DBS) for Parkinson's disease differ from other treatments?

The Movement task treatment, also known as deep brain stimulation (DBS), is unique because it involves surgically implanting electrodes in specific brain areas to modulate abnormal neuronal activity patterns, which can improve motor symptoms like rigidity and bradykinesia. Unlike medications that primarily target dopamine levels, DBS directly alters brain circuits involved in movement control, offering an alternative for patients with advanced Parkinson's disease who do not respond well to drugs. ^{6 7 8 9 10}

What data supports the effectiveness of the treatment Movement task, DBS for Parkinson's Disease?

Research shows that deep brain stimulation (DBS) improves motor symptoms in Parkinson's disease by changing brain activity patterns, leading to better movement control. It is particularly effective when targeting specific brain areas like the subthalamic nucleus and globus pallidus internus, which help reduce symptoms like tremors and rigidity. ^{10 11 12 13 14}

Are You a Good Fit for This Trial?

This trial is for people with advanced Parkinson's disease who are already scheduled for deep brain stimulation surgery. They should be able to cooperate during an awake procedure and have symptoms that improve with L-dopa or have a medication-refractory disabling tremor. Participants must not have cognitive impairments, psychiatric diseases, or medical conditions that rule out surgery.

Inclusion Criteria

I have Parkinson's with symptoms like tremor, stiffness, or slow movement.

I am having deep brain stimulation for Parkinson's with specific symptoms and MRI findings.

Exclusion Criteria

Significant cognitive or psychiatric disease based on clinical neuropsychological testing

I cannot undergo surgery due to medical reasons, including recent use of blood thinners.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Intraoperative Recording

Participants perform movement tasks during awake DBS surgery with intraoperative recordings of brain signals

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Movement task

Trial Overview The study aims to understand how certain stimuli facilitate movement in Parkinson's patients by recording brain activity during DBS surgery. Patients will perform movement tasks while awake, which could help identify new targets for treating symptoms unresponsive to current therapies.

How Is the Trial Designed?

Group I: Parkinson disease patients Experimental Treatment 1 Intervention

Parkinson disease patients undergoing DBS Surgery of the Globus Pallidus Internus (GPi) for clinical indications

Movement task is already approved in United States for the following indications:

Approved in United States as DBS for:

• Parkinson's disease (tremor, advanced symptoms, earlier stages with motor symptoms not adequately controlled with medication)
• Essential tremor
• Multiple sclerosis

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Published Research Related to This Trial

In a study involving seven Parkinson's disease patients, continuous deep brain stimulation (DBS) resulted in significantly shorter movement times during wrist tasks compared to a 0.1-second cycling pattern, indicating that stimulation patterns can affect motor performance.

The findings suggest that the effectiveness of DBS may depend on the specific stimulation pattern used, highlighting the importance of optimizing stimulation protocols for better therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of subthalamic nucleus stimulation patterns on motor performance in Parkinson's disease. Montgomery, EB.[2005]

Deep brain stimulation (DBS) at a therapeutic frequency of 135 Hz significantly alters neuronal activity in the primary motor cortex (M1) of a monkey with Parkinson's disease, leading to improved motor symptoms by changing firing patterns and rates in the pallido-thalamocortical circuit.

Sub-therapeutic DBS (30 Hz) did not enhance motor responses or change discharge rates in M1, indicating that effective symptom relief is linked to specific stimulation parameters that modulate neuronal activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pallidal stimulation that improves parkinsonian motor symptoms also modulates neuronal firing patterns in primary motor cortex in the MPTP-treated monkey. Johnson, MD., Vitek, JL., McIntyre, CC.[2021]

In a study of 40 Parkinson's disease patients undergoing subthalamic deep brain stimulation (STN-DBS), 45% reported significant improvement in sleep quality at 6 months, although this improvement was not statistically significant at 12 months.

The most common benefits included better overall sleep quality and maintenance, but some patients experienced new-onset daytime sleepiness, indicating that while STN-DBS can improve sleep, the effects can vary widely among individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in Parkinson's disease sleep symptoms and daytime somnolence after bilateral subthalamic deep brain stimulation in Parkinson's disease. Kharkar, S., Ellenbogen, JR., Samuel, M., et al.[2020]

Deep brain stimulation (DBS) is effective for treating motor symptoms of Parkinson's disease, particularly when targeting the subthalamic nucleus and globus pallidus internus, which consistently improve motor features.

While some non-motor symptoms also show improvement with DBS, further research is needed to understand these effects better and to explore other deep brain targets like the pedunculopontine nucleus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of motor and non-motor features of Parkinson's disease with deep brain stimulation. Fasano, A., Daniele, A., Albanese, A.[2022]

Deep brain stimulation (DBS) is an established treatment for motor symptoms in advanced Parkinson's disease, but its effects on sleep-wake disturbances (SWD) are not well understood and remain controversial.

The review discusses how DBS may improve SWD not only through direct effects on brain circuits but also indirectly by alleviating nocturnal motor complications and reducing the need for dopaminergic medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Deep Brain Stimulation on Sleep-Wake Disturbances in Patients with Parkinson's Disease: A Narrative Review. Jung, YJ., Kim, HJ., Paek, SH., et al.[2022]

Deep brain stimulation (DBS) is an effective surgical treatment for movement disorders like Parkinson's disease and dystonia, targeting areas such as the subthalamic nucleus (STN) and globus pallidus internus (GPi).

DBS not only improves motor functions but can also affect cognitive and emotional aspects of patients, highlighting the need for careful target selection and consideration of potential adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Critical reappraisal of DBS targeting for movement disorders. Guzzi, G., Della Torre, A., Chirchiglia, D., et al.[2017]

Deep brain stimulation (DBS) can improve motor function and quality of life in patients with Parkinson's disease when used alongside traditional medication, particularly for those whose symptoms are not well-controlled by medication alone.

However, while DBS offers significant benefits, it also comes with a higher risk of adverse events compared to pharmacotherapy, highlighting the need to carefully consider the risks and benefits before opting for this surgical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of deep brain stimulation as an adjunct to pharmacotherapy for the treatment of Parkinson disease. Sharma, A., Szeto, K., Desilets, AR.[2012]

Deep brain stimulation (DBS) for Parkinson's disease, particularly targeting the subthalamic nucleus (STN), provides significant motor improvement and allows for reduced medication doses, making it a preferred option for younger patients with motor complications.

While STN DBS has advantages like better motor control and lower current consumption, it requires more intensive postoperative management and carries risks such as infection and hematoma, though the overall benefit-to-risk ratio is considered favorable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment results: Parkinson's disease. Pollak, P., Fraix, V., Krack, P., et al.[2019]

Deep brain stimulation (DBS) is a safe and effective surgical treatment for advanced Parkinson's disease, with a low incidence of serious complications, as shown in a study of 130 patients over several years.

In this study, 62% of patients experienced no complications, and the most common issues were minor, such as aborted procedures (5.14%) and seizures (4.7%), indicating that DBS has a favorable safety profile compared to other surgical options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications in subthalamic nucleus stimulation surgery for treatment of Parkinson's disease. Review of 272 procedures. Seijo, FJ., Alvarez-Vega, MA., Gutierrez, JC., et al.[2019]

A review of 221 unique adverse events related to deep brain stimulation (DBS) devices for Parkinson's disease revealed that the most common complications were infections (16.2%) and lead migrations (8.6%).

Over 40% of the reported adverse events required patients to return to the operating room for device explantation or revision, highlighting the need for further research to improve the safety and reliability of DBS systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterizing Complications of Deep Brain Stimulation Devices for the Treatment of Parkinsonian Symptoms Without Tremor: A Federal MAUDE Database Analysis. Bennett, J., MacGuire, J., Novakovic, E., et al.[2023]

In a study involving 6 patients with Parkinson's disease, therapeutic deep brain stimulation (DBS) of the subthalamic nucleus normalized brain activation patterns during movement, particularly increasing activity in areas like the supplementary motor area and cerebellum.

Effective DBS not only improved movement execution but also reduced compensatory overactivity in various brain regions, suggesting a more efficient motor control system in patients with Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Normalizing motor-related brain activity: subthalamic nucleus stimulation in Parkinson disease. Grafton, ST., Turner, RS., Desmurget, M., et al.[2021]

In a study involving 12 Parkinson's disease patients and 18 healthy subjects, fMRI revealed that patients exhibited reduced activation in key brain areas (striatum and substantia nigra) during movement initiation, indicating impaired motor control.

During movement inhibition, patients showed decreased activation in the subthalamic nucleus and increased thalamo-cortical activation, suggesting a shift in how their brains process movement control compared to healthy individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebral activations related to ballistic, stepwise interrupted and gradually modulated movements in Parkinson patients. Toxopeus, CM., Maurits, NM., Valsan, G., et al.[2021]

In a study involving 6 patients with Parkinson's disease (PD) and 6 control subjects, PET scans revealed that while normal subjects showed robust activation in several brain areas during free-choice movement tasks, PD patients exhibited impaired activation in key regions like the putamen and anterior cingulate.

The findings suggest that the impaired activation of medial frontal areas in PD patients may contribute to their difficulties in initiating movements, highlighting the impact of nigral degeneration on cortical function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impaired mesial frontal and putamen activation in Parkinson's disease: a positron emission tomography study. Playford, ED., Jenkins, IH., Passingham, RE., et al.[2016]

The study involved 20 patients with Parkinson's disease and 20 healthy controls, using deep brain stimulation to explore how different pathways in the brain affect motor control and cognitive adaptation during movement tasks.

Findings indicate that while deep brain stimulation can modulate motor functions, it does not fully restore cognitive flexibility or kinematic control, suggesting that targeted stimulation strategies could enhance treatment efficacy and reduce side effects in Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional segregation of basal ganglia pathways in Parkinson's disease. Neumann, WJ., Schroll, H., de Almeida Marcelino, AL., et al.[2019]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Effect of subthalamic nucleus stimulation patterns on motor performance in Parkinson's disease. [2005]

2. United States pubmed.ncbi.nlm.nih.gov

Pallidal stimulation that improves parkinsonian motor symptoms also modulates neuronal firing patterns in primary motor cortex in the MPTP-treated monkey. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Changes in Parkinson's disease sleep symptoms and daytime somnolence after bilateral subthalamic deep brain stimulation in Parkinson's disease. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Treatment of motor and non-motor features of Parkinson's disease with deep brain stimulation. [2022]

5. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Effects of Deep Brain Stimulation on Sleep-Wake Disturbances in Patients with Parkinson's Disease: A Narrative Review. [2022]

6. Italy pubmed.ncbi.nlm.nih.gov

Critical reappraisal of DBS targeting for movement disorders. [2017]

7. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of deep brain stimulation as an adjunct to pharmacotherapy for the treatment of Parkinson disease. [2012]

8. United States pubmed.ncbi.nlm.nih.gov

Treatment results: Parkinson's disease. [2019]

9. Austria pubmed.ncbi.nlm.nih.gov

Complications in subthalamic nucleus stimulation surgery for treatment of Parkinson's disease. Review of 272 procedures. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Characterizing Complications of Deep Brain Stimulation Devices for the Treatment of Parkinsonian Symptoms Without Tremor: A Federal MAUDE Database Analysis. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Normalizing motor-related brain activity: subthalamic nucleus stimulation in Parkinson disease. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Cerebral activations related to ballistic, stepwise interrupted and gradually modulated movements in Parkinson patients. [2021]

13. United States pubmed.ncbi.nlm.nih.gov

Impaired mesial frontal and putamen activation in Parkinson's disease: a positron emission tomography study. [2016]

14. England pubmed.ncbi.nlm.nih.gov

Functional segregation of basal ganglia pathways in Parkinson's disease. [2019]