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

2 Participants Needed

Trial Summary

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.

Is deep brain stimulation generally safe for humans?

Deep brain stimulation (DBS) has been used for conditions like Parkinson's disease, with some reported complications such as infections and device issues. These complications sometimes require additional surgery, but the treatment is generally considered safe for many patients. ^{1 2 3 4 5}

How is the VERCISE GENUS™ system treatment different from other Alzheimer's treatments?

The VERCISE GENUS™ system uses deep brain stimulation (DBS), which involves delivering electrical impulses to specific brain areas to potentially slow cognitive decline in Alzheimer's patients. This approach is unique because it targets brain circuitry rather than the traditional focus on amyloid and tau proteins, which are common in other Alzheimer's treatments. ^{3 4 6 7 8}

What is the purpose of this trial?

This project will investigate the potential of Deep Brain Stimulation to improve cognitive abilities and counteract the effects of Alzheimer's disease. Deep Brain Stimulation electrodes targeting the Nucleus Basalis of Meynert (NB) will be implanted bilaterally in a cohort of patients. NB is the sole source of acetylcholine to the neocortex. Such stimulation may not only treat the cognitive symptoms but may have disease-modifying effects. Drawing from animal experiments in non-human primates that showed success of this approach, intermittent stimulation will be delivered at 60 pulses per second for 20 seconds of each minute for one hour per day. The study team will recruit patients, shortly after first being diagnosed with Alzheimer's disease. The study design will test the safety and efficacy of stimulation, potential benefits in cognitive function assessed with a battery of neurocognitive tests, cholinergic neurotransmission evaluated with Positron Emission Tomography, and ability to reverse Alzheimer's biomarkers, including beta amyloid and tau in the cerebrospinal fluid. Successful completion of this project will lead to a potential new intervention for the cognitive impairments of Alzheimer's disease.

Research Team

Dave Blake, PhD

Principal Investigator

Augusta University

Dario Englot, MS, PhD, MD

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

References

1. 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]

2. United States 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). [2011]

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

Increased cerebral metabolism after 1 year of deep brain stimulation in Alzheimer disease. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Brain Stimulation in Alzheimer's Disease. [2018]

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

Deep Brain Stimulation Targets, Technology, and Trials: Two Decades of Progress. [2019]

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

Deep Brain Stimulation for Alzheimer's Disease: Tackling Circuit Dysfunction. [2022]

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

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

8. Germany pubmed.ncbi.nlm.nih.gov

Effects of short- and long-term neurostimulation (tDCS) on Alzheimer's disease patients: two randomized studies. [2022]