Deep Brain Stimulation for Alzheimer's Disease

(DBS-PPN-AD Trial)

Overseen By Steven Carcone

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Disqualifiers: Brain abnormalities, Neurologic, Psychiatric, others

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

Compensation: Varies

Number of Visits: 6

Duration: 12 months

6 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not be taking an acetylcholinesterase inhibitor or memantine unless you have been on a stable dose for at least six months.

What data supports the effectiveness of the treatment Deep Brain Stimulation of the Pedunculopontine Nucleus for Alzheimer's Disease?

Deep Brain Stimulation of the Pedunculopontine Nucleus has shown promise in improving gait and reducing falls in patients with Parkinson's disease, suggesting it may help with movement-related symptoms. However, its effectiveness specifically for Alzheimer's Disease is not directly supported by the available research. ^{1 2 3 4 5}

Is deep brain stimulation of the pedunculopontine nucleus safe for humans?

Deep brain stimulation of the pedunculopontine nucleus has been explored in Parkinson's disease, and while it is a novel approach, the research suggests that unilateral stimulation might reduce surgical risks compared to bilateral stimulation. ^{2 3 6 7 8}

How is Deep Brain Stimulation of the Pedunculopontine Nucleus different from other treatments for Alzheimer's Disease?

Deep Brain Stimulation (DBS) of the Pedunculopontine Nucleus is unique because it targets a specific area of the brain to potentially improve symptoms like gait and balance, which is different from typical Alzheimer's treatments that focus on medication to manage memory and cognitive symptoms. This approach is novel as it uses electrical stimulation rather than drugs. ^{2 3 6 9 10}

What is the purpose of this trial?

Alzheimer's disease (AD) is a brain disorder that gradually impacts cognitive functions such as memory, thinking, and daily functioning. Gamma oscillations are a type of brain activity thought to play a role in memory and cognition (thinking abilities). In AD, these oscillations are impaired - meaning they are smaller and slower than the brain waves observed in healthy individuals. Research suggests that enhancing these brain waves may help slow the progression of AD. This research is investigating a technique called deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) as an experimental intervention. An electrode will be implanted in the PPN and deliver mild stimulation over the course of a 12-month period. As a novel intervention, the priority of the study is to determine if DBS-PPN is a safe and feasible intervention for mild-AD. Additionally, the study investigators are evaluating whether DBS-PPN can increase natural gamma oscillations in ways that improve memory and cognition. The insights from this study will guide the design of an accessible larger trial to more definitively assess how effective DBS-PPN could be as a treatment for AD. Participants will: * Undergo a 12-month experimental intervention involving DBS of the PPN. The procedure for implanting the DBS device takes approximately 2-3 hours under general anesthesia, followed by an overnight stay in the hospital for safety monitoring. * Be required to attend regular appointments every 3 months from DBS implantation for the duration of the study. The follow-up visits will include safety and feasibility monitoring, brain scans (EEG and MEG), and cognitive assessments/questionnaires. * Participants' caregiver will also complete questionnaires about their cognition, functioning, and overall health at the follow-up visits.

Research Team

Taufik A. Valiante, MD PhD FRCS

Principal Investigator

University Health Network, Toronto

Eligibility Criteria

This trial is for individuals with mild Alzheimer's Disease. Participants will have a device implanted in their brain to stimulate the pedunculopontine nucleus and must attend regular follow-up appointments over 12 months. Caregivers are also involved in providing information.

Inclusion Criteria

Clinical dementia rating scale global score of ≤ 1

Fluent in English

Caregiver available to participate in the study

Exclusion Criteria

I do not have significant brain abnormalities like tumors or strokes.

I don't have any mental or other health issues that would stop me from having surgery.

I am not fluent in English, which makes taking cognitive tests in English difficult for me.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

DBS Implantation

Participants undergo a procedure to implant the DBS device in the PPN, followed by an overnight hospital stay for safety monitoring

1 week

1 visit (in-person)

Treatment

Participants receive deep brain stimulation of the PPN over a 12-month period, with regular follow-up visits every 3 months

12 months

4 visits (in-person) at 3-month intervals

Follow-up

Participants are monitored for safety and effectiveness after treatment, including cognitive assessments and caregiver questionnaires

3 months

1 visit (in-person)

Treatment Details

Interventions

• Deep Brain Stimulation of the Pedunculopontine Nucleus

Trial Overview The study tests deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) to see if it can improve memory and thinking by enhancing gamma oscillations in the brain, which are usually impaired in Alzheimer's patients.

Participant Groups

Group I: Deep Brain Stimulation of the Pedunculopontine Nucleus Experimental Treatment 1 Intervention

The experimental intervention employs deep brain stimulation (DBS), a neuromodulation therapy involving the precise application of electrical impulses to targeted brain regions (the PPN) to modulate neural activity. The study intervention will span 12 months, with key milestones including DBS-PPN implantation, DBS activation and initial programming, and follow-up assessments at 3-month intervals. These follow-up visits will assess safety, feasibility, electrographic measures, and cognitive outcomes. All patient participants will receive the experimental intervention. This is the only arm in this study.

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Alzheimer Society of Canada

Collaborator

Trials

10

Recruited

2,900+

Brain Canada

Collaborator

Trials

22

Recruited

6,100+

References

1. England pubmed.ncbi.nlm.nih.gov

Bilateral deep brain stimulation of the pedunculopontine and subthalamic nuclei in severe Parkinson's disease. [2019]

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

The clinical effects of deep brain stimulation of the pedunculopontine tegmental nucleus in movement disorders may not be related to the anatomical target, leads location, and setup of electrical stimulation. [2013]

3. England pubmed.ncbi.nlm.nih.gov

Clinical outcomes from bilateral versus unilateral stimulation of the pedunculopontine nucleus with and without concomitant caudal zona incerta region stimulation in Parkinson's disease. [2012]

4. England pubmed.ncbi.nlm.nih.gov

Unilateral pedunculopontine stimulation improves falls in Parkinson's disease. [2022]

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

Clinicopathological study in progressive supranuclear palsy with pedunculopontine stimulation. [2012]

6. Austria pubmed.ncbi.nlm.nih.gov

Pedunculopontine stimulation from primate to patient. [2021]

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

The peripeduncular nucleus: a novel target for deep brain stimulation? [2007]

8. England pubmed.ncbi.nlm.nih.gov

The peripeduncular nucleus: a novel target for deep brain stimulation? [2007]

9. England pubmed.ncbi.nlm.nih.gov

Deep brain stimulation of the pedunculopontine nucleus for treatment of gait and balance disorder in progressive supranuclear palsy: Effects of frequency modulations and clinical outcome. [2019]

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

Computer-assisted automatic localization of the human pedunculopontine nucleus in T1-weighted MR images: a preliminary study. [2009]