Deep Brain Stimulation for Alzheimer's Disease

Overseen By Chrissy Suell

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Vanderbilt University Medical Center

Must be taking: Cognitive enhancers

Disqualifiers: Psychiatric illness, CNS condition, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Deep Brain Stimulation (DBS) can improve memory and thinking skills in individuals with early-stage Alzheimer's disease. DBS involves placing tiny electrodes in the brain to send electrical pulses, potentially managing symptoms and slowing disease progression. The trial uses the Boston Scientific VERCISE GENUS™ system for this purpose. Researchers seek participants recently diagnosed with Alzheimer's who can still live at home. The study aims to test the safety and effectiveness of DBS, potentially leading to a new treatment for Alzheimer's cognitive issues. As an unphased trial, it offers a unique opportunity to contribute to groundbreaking research that could transform Alzheimer's treatment.

Will I have to stop taking my current medications?

The trial requires that your current medications, including cognitive enhancers and other medications like psychotropics, be stable. This means you should not change your medication doses for at least 60 days before joining the study.

What prior data suggests that this Deep Brain Stimulation technique is safe for Alzheimer's patients?

Research shows that the Vercise Genus Deep Brain Stimulation (DBS) system is generally well-tolerated by patients. In one study, 96% of patients reported feeling better after using DBS. However, some risks exist. For example, the system can be dangerous if exposed to certain conditions, such as diathermy, a type of heat treatment. The FDA has approved the Vercise Genus system for other uses, indicating it has been found safe for humans in those cases. Prospective trial participants should remember that a medical team will closely monitor their health and safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Deep Brain Stimulation (DBS) for Alzheimer's Disease because it offers a unique approach compared to standard treatments like medications that target symptoms. Unlike traditional therapies that primarily aim to manage memory and cognitive decline, DBS involves implanting a device that delivers electrical stimulation directly to specific brain regions. This method aims to modulate brain circuits and potentially slow down or alter the progression of the disease. The VERCISE GENUS™ system used in this treatment allows for precise control of stimulation, which could lead to more personalized and effective management of Alzheimer's symptoms.

What evidence suggests that Deep Brain Stimulation is effective for Alzheimer's disease?

Research has shown that deep brain stimulation (DBS) targeting the Nucleus Basalis of Meynert may enhance thinking and memory in people with Alzheimer's disease. In this trial, participants will receive DBS using the Boston Scientific VERCISE GENUS system. Earlier studies with this system reported that 96% of patients and 94% of doctors observed improvements after DBS. This technique targets a brain area that produces acetylcholine, a chemical crucial for memory and learning. Animal studies have also demonstrated positive results, suggesting this approach might alter the disease itself, not just its symptoms. Overall, these findings support the potential effectiveness of DBS for Alzheimer's. ^{1 2 4 6 7}

Who Is on the Research Team?

Dave Blake, PhD

Principal Investigator

Augusta University

Dario Englot, MS, PhD, MD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for early-stage Alzheimer's patients with mild cognitive impairment or dementia, scoring 23 or higher on the MMSE. Participants need a caregiver, must be living at home, and have stable medication use. They can't join if they have severe psychiatric illnesses, other brain conditions like Parkinson's disease, substance abuse issues, are unable to undergo PET/MRI scans or tolerate anesthesia.

Inclusion Criteria

I have been diagnosed with early-stage Alzheimer's or memory loss.

I've been on a stable dose of medication for memory problems, equivalent to or less than 10 mg/day of donepezil, for at least 60 days.

Clinical Dementia Rating (CDR) global score of 0.5-1.0 with a memory box score of at least 0.5

Exclusion Criteria

Current major psychiatric disorder such as schizophrenia, bipolar disorder or major depressive disorder based on psychiatric consult at screening visit

I cannot undergo certain medical procedures due to health issues or implants.

I cannot undergo surgery with general anesthesia.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Deep Brain Stimulation electrodes are implanted and intermittent stimulation is delivered daily for the first 12 months

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, with cognitive function assessed and biomarkers evaluated

12-24 months

What Are the Treatments Tested in This Trial?

Interventions

• Boston Scientific, VERCISE GENUS™ system

Trial Overview The study tests Deep Brain Stimulation (DBS) using the VERCISE GENUS™ system targeting the Nucleus Basalis of Meynert in Alzheimer's patients. It aims to improve cognition and potentially modify the disease by delivering intermittent stimulation daily and measuring cognitive function changes along with Alzheimer’s biomarkers.

How Is the Trial Designed?

Group I: Deep Brain Stimulation Experimental Treatment 2 Interventions

Patients who are implanted and receive intermittent stimulation daily for the first 12 months

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Boston Scientific Corporation

Industry Sponsor

Trials

758

Recruited

867,000+

Michael F. Mahoney

Boston Scientific Corporation

Chief Executive Officer since 2016

MBA from Wake Forest University, BBA in Finance from the University of Iowa

Kenneth Stein

Boston Scientific Corporation

Chief Medical Officer since 2020

MD from Harvard Medical School, MMSc in Clinical Investigation from Harvard-MIT Division of Health Sciences and Technology

Published Research Related to This Trial

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]

A study using the Deep Brain Stimulation Brain Tissue Network's database found no adverse clinical or pathological effects from performing 1.5 T MRI scans on patients with implanted DBS devices, suggesting that MRI is relatively safe for these patients.

Further examination of post-mortem brains with DBS leads exposed to prolonged 3T MRI also showed no evidence of heat-related damage, supporting the safety of higher field strength MRI in DBS patients under current guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of human brain tissue post-magnetic resonance imaging: information from the National Deep Brain Stimulation Brain Tissue Network (DBS-BTN). Ullman, M., Vedam-Mai, V., Krock, N., et al.[2011]

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]

In a phase I study involving 5 patients with mild Alzheimer's disease, deep brain stimulation (DBS) targeting the fornix significantly increased cerebral glucose metabolism in key brain networks after one year, suggesting enhanced neural activity.

The increased metabolism was correlated with improved clinical outcomes in cognition, memory, and quality of life, indicating that DBS may offer a more extensive and effective treatment option compared to traditional pharmacotherapy for Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased cerebral metabolism after 1 year of deep brain stimulation in Alzheimer disease. Smith, GS., Laxton, AW., Tang-Wai, DF., et al.[2021]

Citations

1. bostonscientific.com bostonscientific.com/en-US/medical-specialties/neurological-surgery/deep-brain-stimulation-system/clinical-data.html

Vercise Genus DBS System clinical data 96% of patients and 94% clinicians reported improvement following deep brain stimulation (DBS). See the full Real-World Outcomes in the USA study. Percent ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05882344?term=Boston%20Scientific%20Vercise&viewType=Table&rank=8

Cholinergic Deep Brain Stimulation for Alzheimer's Disease This project will investigate the potential of Deep Brain Stimulation to improve cognitive abilities and counteract the effects of Alzheimer's disease.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8959612/

Past, Present, and Future of Deep Brain Stimulation As the technology for DBS continues to progress, treatment efficacy will continue to improve and disease indications will expand. Hardware advances such as ...

4. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf15/P150031C.pdf

Vercise™ Deep Brain Stimulation with the Boston Scientific DBS System may damage the system, diminish the effectiveness of therapy, and/or put the patient at unknown risk. A backup device ...

5. bostonscientific.com bostonscientific.com/content/dam/bostonscientific/neuro/eu/visualization/boston-scientific-broucher-visualization.pdf

Deep Brain Stimulation (DBS) Clinical Compendium The success of DBS outcomes may depend on the precise density and location of a stimulation field targeting a specific area of the brain.

6. bostonscientific.com bostonscientific.com/en-US/products/deep-brain-stimulation-systems/vercise-genus-dbs-system-indications-safety-and-warning.html

Vercise Genus DBS System Indications, Safety and Warning The energy generated by diathermy can be transferred to the Boston Scientific DBS System, causing tissue damage in the brain resulting in severe injury or death ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2214751925000477

Innovative developments in deep brain stimulation devices Technological innovations in DBS improve stimulation precision and expand clinical indications. Closed-loop DBS enables real-time adaptive stimulation.