Brain Stimulation for Parkinson's Disease Dementia

(SHARPEN Trial)

Recruiting at 1 trial location

Overseen By Kara Richardson

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Scion NeuroStim

Must not be taking: Antipsychotics

Disqualifiers: Severe dementia, Recent stroke, others

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

Compensation: Varies

Number of Visits: 5

Duration: 12 weeks

9 Participants Needed

Trial Summary

Do I need to stop taking my current medications for this trial?

The trial requires that you stay on your current Parkinson's disease medications and not introduce new ones during the study.

What data supports the idea that Brain Stimulation for Parkinson's Disease Dementia is an effective treatment?

The available research shows that deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) has been explored as a treatment for Parkinson's Disease Dementia. Some studies suggest that low-frequency stimulation of this area can have positive effects on cognitive function in individual patients. However, larger studies are needed to confirm these findings. Additionally, unintentional high-frequency stimulation in a small group of patients did not lead to a faster decline in cognitive function, indicating that the treatment might be safe. Overall, while there are promising signs, more research is needed to fully understand the effectiveness of this treatment compared to other options. ^{1 2 3 4 5}

What safety data exists for non-invasive brain stimulation for Parkinson's Disease Dementia?

The provided research primarily discusses safety data related to Deep Brain Stimulation (DBS), which is an invasive procedure. Common complications of DBS include infections, lead migrations, and device malfunctions, with overall complication rates exceeding 25% and permanent neurologic sequelae in 4-6% of cases. However, this data does not directly address non-invasive brain stimulation methods, which may have different safety profiles. Further research specific to non-invasive techniques is needed to provide relevant safety data. ^{6 7 8 9 10}

Is non-invasive brainstem stimulation a promising treatment for Parkinson's disease dementia?

The research articles mainly discuss deep brain stimulation, which is a different method than non-invasive brainstem stimulation. Therefore, based on the provided information, we cannot determine if non-invasive brainstem stimulation is promising for Parkinson's disease dementia. ^{2 4 5 6 11}

What is the purpose of this trial?

The purpose of this single arm study is to evaluate the feasibility and safety of treatments with a non-invasive neuromodulation device in adults diagnosed with mild/moderate Parkinson's disease dementia (PDD). A non-invasive device is a device that stays outside of the body and is not implanted and does not penetrate the skin. Neuromodulation means that the device stimulates activity in the brain.

Eligibility Criteria

This trial is for adults with mild/moderate Parkinson's Disease Dementia (PDD) who've had a positive response to levodopa treatment for at least one year. They must be on stable PD medication regimens and have a partner available more than three hours daily, five days a week, to assist in the study.

Inclusion Criteria

You must have an adherent study partner (someone who sees you for more than three hours a day, 5x weekly) that is willing to give consent and take part in the trial.

I have been diagnosed with probable Parkinson's disease dementia.

I can maintain my current Parkinson's disease treatment without changes during the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants self-administer treatments twice daily using a non-invasive neuromodulation device over a period of 12 weeks

12 weeks

4 visits (in-person), multiple phone calls

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Non-invasive brainstem stimulation

Trial Overview The SHARPEN study tests the safety and feasibility of using non-invasive brainstem stimulation as a treatment. This device stimulates brain activity from outside the body without needing surgical implantation or skin penetration.

Participant Groups

Group I: Investigational Treatment Experimental Treatment 1 Intervention

Time-varying caloric vestibular stimulation

Who Is Running the Clinical Trial?

Scion NeuroStim

Lead Sponsor

Trials

14

Recruited

550+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Findings from Research

Deep brain stimulation (DBS) has been explored as a treatment for dementia, with three studies focusing on its effects, including one on fornix DBS for Alzheimer's disease and two on nucleus basalis of Meynert for Alzheimer's and Parkinson's disease dementia.

Current evidence for the effectiveness of DBS in treating dementia is still preliminary and limited, indicating a need for further research to understand its potential clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for the treatment of Alzheimer disease and dementias. Laxton, AW., Lozano, AM.[2022]

Deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) was safely performed in a small group of 6 patients with Parkinson disease dementia, with no serious adverse events reported during the trial.

While no significant improvements were found in primary cognitive outcomes, NBM DBS did show a notable reduction in neuropsychiatric symptoms, suggesting potential benefits that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bilateral Deep Brain Stimulation of the Nucleus Basalis of Meynert for Parkinson Disease Dementia: A Randomized Clinical Trial. Gratwicke, J., Zrinzo, L., Kahan, J., et al.[2022]

Deep brain stimulation (DBS) targeting the nucleus basalis of Meynert shows promise in enhancing cognitive function and potentially slowing the progression of Alzheimer's disease, based on recent human and animal studies.

The effectiveness of DBS may depend on stimulation parameters, with lower frequencies or intermittent patterns likely being more beneficial for cognitive enhancement compared to the high-frequency stimulation used for movement disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cholinergic Deep Brain Stimulation for Memory and Cognitive Disorders. Subramaniam, S., Blake, DT., Constantinidis, C.[2023]

In a clinical trial involving 6 patients with Lewy body dementia, NBM-DBS did not show significant cognitive benefits compared to sham stimulation, indicating it may not be effective for improving memory recall in this population.

While the surgical procedure for NBM-DBS was well tolerated, there were notable declines in certain cognitive assessments after electrode implantation, suggesting potential safety concerns associated with the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nucleus Basalis of Meynert Stimulation for Lewy Body Dementia: A Phase I Randomized Clinical Trial. Maltête, D., Wallon, D., Bourilhon, J., et al.[2022]

In a study of 33 Parkinson's disease patients with high-frequency deep brain stimulation (DBS) in the internal Globus pallidus (GPi), unintentional stimulation of the nucleus basalis of Meynert (NBM) did not lead to a significant decline in cognitive function over one year.

These findings suggest that high-frequency NBM-DBS may not have the detrimental effects on cognition that were initially hypothesized, indicating a need for further research to explore the therapeutic potential of NBM-DBS in treating cognitive symptoms associated with Parkinson's disease dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serendipitous Stimulation of Nucleus Basalis of Meynert-The Effect of Unintentional, Long-Term High-Frequency Stimulation on Cognition in Parkinson's Disease. Bogdan, ID., Oterdoom, DLM., van Laar, T., et al.[2022]

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 is an effective treatment for movement disorders, involving an implanted electrode and pulse generator, but its mechanisms of action are not fully understood and were developed without extensive preclinical safety studies.

Complication rates for deep brain stimulation can exceed 25%, with 4-6% of patients experiencing permanent neurological issues, highlighting the need for better understanding of adverse events and safer stimulation methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety considerations for deep brain stimulation: review and analysis. Grill, WM.[2007]

Deep brain stimulation (DBS) is an effective treatment for various disorders, including movement and epilepsy disorders, but it is vulnerable to external electromagnetic interference (EMI) that can cause device malfunction or tissue injury.

The study highlights the need for more comprehensive guidelines on EMI sources, as real-world instances of interference from devices like MRI scans and airport body scanners have been documented, indicating potential risks for patients with DBS devices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation and electromagnetic interference. Rahimpour, S., Kiyani, M., Hodges, SE., et al.[2022]

Deep Brain Stimulation (DBS) for Parkinson's disease can lead to rare complications, such as an intracranial abscess, as demonstrated in a case involving a 59-year-old male who developed significant inflammation and required multiple surgeries after the procedure.

Despite the complications, the patient's Parkinson's symptoms improved after the abscess was surgically drained, suggesting that the abscess may have inadvertently provided some therapeutic benefit similar to a subthalomotomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracerebral abscess: a rare complication of Deep Brain Stimulation. Brandão, E., Rosas, MJ., Abreu, P., et al.[2013]

Deep brain stimulation (DBS) is effective for managing parkinsonian symptoms, but in rare cases, it can lead to severe mood disruptions, as demonstrated by a 58-year-old woman who developed rapid-onset depression during a routine battery replacement procedure after 5 years of DBS treatment.

Electroconvulsive therapy (ECT) proved to be an effective treatment for the patient's severe depression, highlighting its potential as a therapeutic option for patients experiencing intractable mood disorders related to DBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Administration of electroconvulsive therapy for depression associated with deep brain stimulation in a patient with post-traumatic Parkinson's Disease: a case study. Cunningham, MG., Yadollahikhales, G., Vitaliano, G., et al.[2018]

In a study of six patients with Parkinson's disease dementia (PDD) who underwent deep brain stimulation of the nucleus basalis of Meynert (NBM-DBS), five patients were followed for three years, showing varying rates of cognitive decline, with two patients experiencing a slower progression.

The study found that better baseline attention and less daytime sleepiness were linked to improved cognitive outcomes after three years, suggesting that individual differences may influence the effectiveness of NBM-DBS in PDD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation of the Nucleus Basalis of Meynert for Parkinson's Disease Dementia: A 36 Months Follow Up Study. Cappon, D., Gratwicke, J., Zrinzo, L., et al.[2022]

References

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

Deep brain stimulation for the treatment of Alzheimer disease and dementias. [2022]

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

Bilateral Deep Brain Stimulation of the Nucleus Basalis of Meynert for Parkinson Disease Dementia: A Randomized Clinical Trial. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Cholinergic Deep Brain Stimulation for Memory and Cognitive Disorders. [2023]

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

Nucleus Basalis of Meynert Stimulation for Lewy Body Dementia: A Phase I Randomized Clinical Trial. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Serendipitous Stimulation of Nucleus Basalis of Meynert-The Effect of Unintentional, Long-Term High-Frequency Stimulation on Cognition in Parkinson's Disease. [2022]

6. 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]

7. England pubmed.ncbi.nlm.nih.gov

Safety considerations for deep brain stimulation: review and analysis. [2007]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Deep brain stimulation and electromagnetic interference. [2022]

9. Spain pubmed.ncbi.nlm.nih.gov

Intracerebral abscess: a rare complication of Deep Brain Stimulation. [2013]

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

Administration of electroconvulsive therapy for depression associated with deep brain stimulation in a patient with post-traumatic Parkinson's Disease: a case study. [2018]

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

Deep Brain Stimulation of the Nucleus Basalis of Meynert for Parkinson's Disease Dementia: A 36 Months Follow Up Study. [2022]