Deep Brain Stimulation for Alzheimer's Disease

Overseen By David T Blake, PhD

Age: 65+

Sex: Any

Trial Phase: Phase 1

Sponsor: Augusta University

Must be taking: Psychopharmacological medication

Disqualifiers: Schizophrenia, Bipolar, Stroke, others

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

Compensation: Varies

Number of Visits: 4

Duration: 2 years

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new procedure called intermittent Deep Brain Stimulation (DBS) to determine if it can help individuals with early-stage Alzheimer's disease maintain or improve their cognitive abilities over two years. Participants in the experimental group will receive daily DBS sessions, while the control group will continue with standard care without this treatment. This trial suits those diagnosed with early Alzheimer's who live at home, have a caregiver, and do not have other types of dementia or major mental health issues. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this innovative procedure.

Will I have to stop taking my current medications?

The trial requires that your current medications, like donepezil, be stable for at least 60 days before joining. This means you should not change your medication dose or start new medications during this time.

What prior data suggests that this procedure is safe for treating Alzheimer's disease?

Research shows that intermittent Deep Brain Stimulation (DBS) on the nucleus basalis of Meynert is generally safe. Studies have found no serious negative effects from this treatment. Patients in these studies experienced no major side effects and tolerated the procedure well. DBS has also improved thinking and memory. Although this trial is still in the early stages, safety results from other studies are encouraging for potential participants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for Alzheimer's, which often involve medications like cholinesterase inhibitors and memantine, intermittent deep brain stimulation targets the brain directly. This technique focuses on the nucleus basalis of Meynert, which is crucial for memory and cognitive function. Researchers are excited because this method could potentially slow cognitive decline more effectively by directly influencing brain activity, offering hope for improved outcomes where traditional medications fall short.

What evidence suggests that intermittent Deep Brain Stimulation might be an effective treatment for Alzheimer's?

This trial will evaluate the effects of intermittent deep brain stimulation (DBS) of the nucleus basalis of Meynert on Alzheimer's disease. Research has shown that DBS in this brain area can improve thinking and memory in Alzheimer's patients. Studies have found that it can enhance memory and self-care skills without worsening the disease. Animal studies support these findings, indicating that stimulating this part of the brain can enhance thinking abilities and increase blood flow. Specifically, one study discovered that occasional stimulation improved working memory, which is crucial for everyday activities. Overall, DBS in this brain region appears promising for helping Alzheimer's patients maintain or even improve cognitive abilities. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals aged 65-85 with early-stage Alzheimer's Disease, confirmed by specific criteria and a positive PET scan for beta amyloid. Participants must have mild cognitive impairment, an available caregiver, live at home, and be on stable Alzheimer's medication. Excluded are those with major psychiatric disorders, recent significant head trauma, other forms of dementia or brain lesions, terminal illness with less than 30 months expected survival, or any unstable medical condition.

Inclusion Criteria

I am 65 years old or older.

I am 85 years old or younger.

I have early-stage Alzheimer's and a positive PET scan for beta amyloid.

Exclusion Criteria

Current major psychiatric disorder such as schizophrenia, bipolar disorder or major depressive disorder based on psychiatric consult at screening visit, or past medical history prior suicidal attempts or suicidal crises

Clinical co-morbidity interfering with study (e.g. head trauma requiring medical treatment in the 2 years prior, brain tumor, subdural hematoma, or other clinically significant space-occupying lesion on brain CT or MRI), or other implant precluding high field MRI scans

Terminal illness associated with expected survival of <30 months

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intermittent deep brain stimulation of the nucleus basalis of Meynert for 50 minutes each day

2 years

Assessments at onset, after 4 weeks, and every 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Intermittent Deep Brain Stimulation of Nucleus Basalis of Meynert

Trial Overview

The study tests intermittent Deep Brain Stimulation (DBS) of the nucleus basalis of Meynert in Alzheimer's patients to see if it can maintain or improve cognition over two years. Twelve participants will be enrolled; half will receive DBS while the other half won't as a control group documenting standard care progression.

How Is the Trial Designed?

Group I: Intermittent deep brain stimulation of the nucleus basalis of Meynert Experimental Treatment 1 Intervention

Subjects will receive intermittent deep brain stimulation of the nucleus basalis of Meynert for 50 minutes each day. Assessments will be performed at onset, after four weeks of intervention, and each six months through two years.

Group II: Control group Active Control 1 Intervention

Subjects will have matching eligility criteria as those in the experimental arm, but will receive no intervention. Assessments will be performed at study onset, and each six months through two years after onset.

Who Is Running the Clinical Trial?

Augusta University

Lead Sponsor

Trials

219

Recruited

85,900+

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11863734/

Deep brain stimulation of the nucleus basalis of Meynert in ...

Results. NBM-DBS was safe, with no severe adverse events. It improved cognitive functions and self-care abilities without altering the disease's ...

2.

nature.com

nature.com/articles/s41598-021-91391-0

Electrical stimulation of the nucleus basalis of meynert

Animal studies have shown that electrical stimulation of the NBM enhanced cognition, increased the release of acetylcholine, enhanced cerebral blood flow.

3.

sciencedirect.com

sciencedirect.com/science/article/pii/S0960982217308795

Intermittent Stimulation of the Nucleus Basalis of Meynert ...

Our results reveal that intermittent NB stimulation can improve working memory, a finding that has implications for restoring cognitive function ...

4.

translationalneurodegeneration.biomedcentral.com

translationalneurodegeneration.biomedcentral.com/articles/10.1186/s40035-022-00327-9

Deep brain stimulation of the nucleus basalis of Meynert ...

The results indicated that NBM-DBS improves short-term cognitive performance in patients with advanced AD, which may be related to the modulation of multi- ...

5.

biorxiv.org

biorxiv.org/content/10.1101/2024.04.05.588271v1.full-text

Deep Brain Stimulation of Nucleus Basalis of Meynert ...

Results Both normal and stimulated rats demonstrated improved performance in NOR and auditory learning as compared to the unstimulated demented ...

6.

brainstimjrnl.com

brainstimjrnl.com/article/S1935-861X(24)00611-9/fulltext

Intermittent Deep Brain Stimulation of the Nucleus Basalis of ...

Our phase I clinical trial confirmed that NBM DBS is safe and achieves cognitive outcomes comparable to traditional treatments.

7.

sciencedirect.com

sciencedirect.com/science/article/pii/S1935861X20300899

Bilateral nucleus basalis of Meynert deep brain stimulation ...

This pilot trial shows that NBM DBS is safe and well tolerated in carefully selected DLB patients. Furthermore, active stimulation was shown to induce changes ...

8.

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.