Brain Stimulation for Parkinson's Disease Dementia

(SHARPEN Trial)

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new brain stimulation device to determine its safety and practicality for individuals with mild to moderate Parkinson's disease dementia (PDD). The device is non-invasive, stimulating brain activity externally. It aims to assist those diagnosed with Parkinson's disease dementia who can maintain their current Parkinson's treatments without introducing new ones. Participants must have a caregiver or someone who spends significant time with them to also participate in the study. As an unphased trial, this study provides an opportunity to contribute to groundbreaking research that could enhance future treatment options.

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 prior data suggests that this non-invasive neuromodulation device is safe for adults with Parkinson's disease dementia?

Research has shown that non-invasive brainstem stimulation has been tested in people with Parkinson's disease. In one study using a similar device, participants reported no major safety issues, and the treatment was generally well-tolerated.

The device for this stimulation does not require surgery or break the skin, making it less risky than treatments that do. Participants in previous studies used the device at home independently, indicating it is easy to use and safe for regular use.

These findings suggest the treatment is safe for humans, but individual reactions may vary. Always consult a doctor before joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for Parkinson's Disease Dementia, such as medications like cholinesterase inhibitors or memantine, aim to manage symptoms by modifying neurotransmitter activity. But non-invasive brainstem stimulation works differently, targeting the brain's vestibular system through time-varying caloric vestibular stimulation. This approach is unique because it uses a non-invasive method to potentially modulate brain activity and improve cognitive function without the side effects associated with traditional medications. Researchers are excited about this because it opens up a new avenue for treatment that could be both effective and less burdensome for patients.

What evidence suggests that this non-invasive neuromodulation device is effective for Parkinson's disease dementia?

In this trial, participants will receive a non-invasive technique called time-varying caloric vestibular stimulation (tvCVS). Studies have shown that tvCVS has been successfully used in people with Parkinson's disease. This method gently stimulates the balance centers in the inner ear, potentially improving movement and other symptoms. Research suggests that this stimulation might reset brain activity to a healthier state, benefiting those with Parkinson's disease dementia. Early trials indicated that this treatment is safe and can be used effectively twice a day. Overall, the evidence is promising but still developing. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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) 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9682273/

Time-varying caloric vestibular stimulation for the treatment ... Using a non-invasive, solid-state delivery device, tvCVS has been successfully used in a human clinical trial with Parkinson's disease (PD) ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11432959/

Vestibular Neurostimulation for Parkinson's Disease: A Novel ... Therapeutic non-invasive vestibular stimulation is a relatively modern concept that may potentially improve a broad range of motor and nonmotor symptoms of PD.

3. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/18/NCT04799418/Prot_000.pdf

STEM-PD, V6.0 -- CONFIDENTIAL Clinician version – not ... This paired set of studies seeks to establish the safety and efficacy of twice daily time-varying caloric vestibular stimulation (tvCVS) ...

4. frontiersin.org frontiersin.org/journals/systems-neuroscience/articles/10.3389/fnsys.2020.00012/full

Sensory Neuromodulation Yet the aim of non-invasive brain stimulation (NIBS) devices is to change the state of brain oscillators, ideally returning them closer to a pre-disease state, ...

5. researchgate.net researchgate.net/publication/382506059_Vestibular_Neurostimulation_for_Parkinson's_Disease_A_Novel_Device_Aided_Noninvasive_Therapeutic_Option

(PDF) Vestibular Neurostimulation for Parkinson's Disease Therapeutic non-invasive vestibular stimulation is a relatively modern concept that may potentially improve a broad range of motor and nonmotor ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05987540

NCT05987540 | SHARPEN - Parkinson's Disease Dementia Study participants will self-administer ~19-minute treatments twice daily in the home setting over 12 weeks using a non-invasive brainstem modulation device.