Accelerated Brain Stimulation for Parkinson's Disease

Overseen By Michael Vesia, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Michigan

Must be taking: Dopamine replacement

Must not be taking: GABAergic, NDMA-receptor antagonist

Disqualifiers: Neurologic disease, Depression, Stroke, others

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

Compensation: Varies

Number of Visits: 7

Duration: 2 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

Parkinson disease (PD) is a common disorder in which reduced speed of movement results from inadequate brain production of the chemical dopamine. The most effective treatment for Parkinson disease is the use of drugs that provide dopamine replacement therapy (DRT). However, as the disease progresses there are prominent DRT-resistant features of Parkinson disease that are a major source of disability. These include cognitive (attention, memory) impairments and gait disorders such as freezing and falls. Repetitive transcranial magnetic stimulation (rTMS), a form of non-invasive brain stimulation, holds promise for the study and treatment of motor and cognitive deficits in persons with Parkinson's. To date, there are no conclusive results regarding an optimal rTMS protocol for recovery of motor and cognitive deficits in Parkinson's disease. This study is designed to promote clinical rehabilitation neuroscience research, and aims to improve rehabilitation in persons with Parkinson's with freezing of gait. This work will evaluate the use of a new accelerated, high dose, non-invasive brain stimulation method for treatment of freezing of gait in PD and will test how applying targeted accelerated stimulation to the brain improves gait disturbance due to PD.

Will I have to stop taking my current medications?

The trial requires that you do not take certain medications that affect brain receptors, like GABAergic drugs or NDMA-receptor antagonists. If you're on these, you might need to stop them to participate.

What data supports the effectiveness of the treatment Function-based Accelerated Stimulation Therapy (FAST-therapy) for Parkinson's Disease?

Research shows that high-frequency deep brain stimulation, similar to FAST-therapy, improves movement speed in Parkinson's patients by targeting brain areas involved in motor control. This type of stimulation has been effective in reducing symptoms like tremors and improving overall motor function, suggesting potential benefits for FAST-therapy. ^{1 2 3 4 5}

Is accelerated brain stimulation therapy safe for humans?

Deep brain stimulation (DBS), a similar treatment, is generally considered safe with low risks of complications like infection, bleeding, or device issues, especially at experienced centers. However, specific safety data for accelerated brain stimulation therapy is not available in the provided research. ^{3 6 7 8 9}

How does FAST-therapy differ from other treatments for Parkinson's disease?

FAST-therapy is unique because it uses accelerated brain stimulation, potentially offering more precise and adaptable treatment compared to traditional deep brain stimulation, which often uses constant settings. This approach may allow for better management of symptoms with fewer side effects by adjusting stimulation based on real-time brain activity. ^{1 3 10 11 12}

Eligibility Criteria

This trial is for English-speaking Parkinson's disease patients aged 45-90, diagnosed based on Movement Disorder Society criteria and in the early stages (H&Y2-3). They must be able to consent. Excluded are those with other neurological diseases, depression (GDS score >11), brain lesions from imaging, implanted medical devices or metal in the head, conditions increasing seizure risk, or serious heart or liver diseases.

Inclusion Criteria

English speaker

My Parkinson's disease is in the early to mid-stage.

Able to provide written consent prior to admission

Exclusion Criteria

I have conditions that could increase my risk of seizures.

Cochlear hearing implants

Depression: Geriatric Depression Scale (GDS) score >11

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive open-label treatment with intermittent theta burst stimulation (iTBS) for six days within a fourteen-day span

2 weeks

6 visits (in-person)

Follow-up

Participants are monitored for changes in functional connectivity and motor function post-treatment

2 weeks

1 visit (in-person)

Treatment Details

Interventions

• Function-based Accelerated Stimulation Therapy (FAST-therapy)

Trial Overview The study tests repetitive transcranial magnetic stimulation (rTMS) as a treatment for freezing of gait in Parkinson's patients. It explores an accelerated high-dose method of non-invasive brain stimulation to improve walking disturbances without relying on drug replacement therapy.

Participant Groups

Group I: Open label treatment Experimental Treatment 1 Intervention

All subjects then will receive open-label treatment (Tx) for six days within an fourteen-day span (Visits 3-8). Briefly, a newer form of rTMS called intermittent theta burst stimulation (iTBS) will be used that mimics endogenous theta rhythms, which can improve induction of synaptic long-term potentiation and influence functional connectivity. A 10-min iTBS sessions will be applied to the basal ganglia-cerebellar-cortical network immediately after the subject has primed and activated the network by performing a precision force tracking task for up to 10 min. The subject will undergo 5 sessions of the force task and stimulation per day, with each session separated by 40 min.

Who Is Running the Clinical Trial?

University of Michigan

Lead Sponsor

Trials

1,891

Recruited

6,458,000+

Findings from Research

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 reversible and adjustable treatment for movement disorders like essential tremor and Parkinson's disease, with a low complication risk of ≤ 5% at experienced centers.

Future advancements in DBS technology include directional brain electrodes and 'closed loop' systems that can adapt stimulation based on real-time brain activity, potentially improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for movement disorders. Larson, PS.[2021]

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]

Deep brain stimulation (DBS) and spinal cord stimulation have been effectively used since the 1960s to treat intractable pain and movement disorders, with high-frequency stimulation (HFS) of the subthalamic nucleus (STN) showing significant benefits for Parkinson's symptoms while reducing the need for medication and its side effects.

Recent advancements in DBS technology, including the use of nanotechnologies and new hardware, are expanding treatment possibilities beyond movement disorders to include conditions like epilepsy, psychiatric disorders, and even obesity, paving the way for innovative neuroprosthetic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional neurosurgery for movement disorders: a historical perspective. Benabid, AL., Chabardes, S., Torres, N., et al.[2009]

References

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

High-frequency deep brain stimulation of the putamen improves bradykinesia in Parkinson's disease. [2021]

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

Insights gleaned by measuring patients' stated goals for DBS: More than tremor. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for Parkinson's disease. [2019]

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

Toward therapeutic electrophysiology: beta-band suppression as a biomarker in chronic local field potential recordings. [2022]

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

Deep brain stimulation of the subthalamic nucleus enhances emotional processing in Parkinson disease. [2019]

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

Treatment results: Parkinson's disease. [2019]

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

Deep brain stimulation for movement disorders. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Drug insight: Continuous dopaminergic stimulation in the treatment of Parkinson's disease. [2013]

9. 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]

10. England pubmed.ncbi.nlm.nih.gov

Subthalamic nucleus deep brain stimulation driven by primary motor cortex γ2 activity in parkinsonian monkeys. [2022]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Functional neurosurgery for movement disorders: a historical perspective. [2009]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Using "smart stimulators" to treat Parkinson's disease: re-engineering neurostimulation devices. [2021]