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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether deep brain stimulation (DBS), which uses mild electrical impulses, can improve memory and thinking abilities in individuals with mild Alzheimer's disease. Researchers focus on the pedunculopontine nucleus (PPN) to determine if boosting certain brain waves can slow the disease's progression. The primary goal is to assess the safety and practicality of this approach. Individuals with mild Alzheimer's, who do not have other brain issues and have a caregiver for support, may be suitable candidates for this study. As an unphased trial, it offers participants the chance to contribute to groundbreaking research that could lead to new treatments for Alzheimer's disease.

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 prior data suggests that this technique is safe for Alzheimer's patients?

Research has shown that deep brain stimulation (DBS) is generally well-tolerated and has been used for other brain disorders. In previous studies, patients reported mild side effects like temporary headaches or dizziness, which usually do not last long. DBS involves placing a small device in the brain to send electrical signals to specific areas, such as the pedunculopontine nucleus (PPN) in this study. As this method is still being tested for Alzheimer's, researchers are carefully monitoring for any possible side effects. Since this is an early study, the main focus is on safety and the feasibility of the treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for Alzheimer's disease focus on medications that aim to manage symptoms or slow disease progression, like cholinesterase inhibitors and memantine. But deep brain stimulation (DBS) is different—it targets the brain's electrical activity directly. DBS involves implanting electrodes in the brain, in this case, the Pedunculopontine Nucleus (PPN), to send precise electrical impulses. Researchers are excited because this approach could modulate neural activity in a way that might improve cognitive function, offering a new avenue for treatment beyond traditional drug therapies.

What evidence suggests that deep brain stimulation of the pedunculopontine nucleus is effective for Alzheimer's disease?

Research suggests that deep brain stimulation (DBS) targeting the pedunculopontine nucleus (PPN) might aid in treating Alzheimer's disease. This brain area connects to gamma waves, crucial for memory and thinking. In Alzheimer's patients, these waves are weaker and slower. Stimulating the PPN aims to strengthen these gamma waves, potentially enhancing memory and cognitive skills. Previous studies have shown that DBS can positively affect brain activity, indicating it could be a promising approach for Alzheimer's. However, this treatment is new, and further research is needed to confirm its effectiveness. Participants in this trial will receive the experimental DBS intervention targeting the PPN to evaluate its safety, feasibility, and effects on cognitive outcomes. ^{1 2 4 6 7}

Who Is on the Research Team?

Taufik A. Valiante, MD PhD FRCS

Principal Investigator

University Health Network, Toronto

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06936124

Study Details | NCT06936124 | Deep Brain Stimulation of ... This study investigates a novel approach using deep brain stimulation (DBS) to target the pedunculopontine nucleus (PPN), a region involved in generating and ...

2. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/594915

Deep Brain Stimulation of the Pedunculopontine Nucleus ... Research suggests that enhancing these brain waves may help slow the progression of AD.

3. trialx.com trialx.com/clinical-trials/listings/297129/deep-brain-stimulation-of-the-pedunculopontine-nucleus-for-alzheimers-disease/

Deep Brain Stimulation of the Pedunculopontine Nucleus ... By stimulating the PPN, the study intervention aims to enhance gamma activity, potentially improving memory and cognition in AD patients.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6397644/

Deep brain stimulation: current challenges and future directions This Review considers how DBS has facilitated advances in our understanding of how circuit malfunction can lead to brain disorders and outlines the key unmet ...

5. frontiersin.org frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2018.00360/full

Deep Brain Stimulation: A Potential Treatment for ... NBM-DBS improved cognitive function in a pilot Phase I study in patients with AD, while in an expanded PDD trial, NBM-DBS failed to improve cognitive function ( ...

6. braincanada.ca braincanada.ca/funded_grants/dbs-ppn-ad-a-pilot-clinical-trial-investigating-deep-brain-stimulation-of-the-pedunculopontine-nucleus-for-thetreatment-of-alzheimers-disease/

DBS-PPN-AD: A Pilot Clinical Trial Investigating Deep ... We are proposing a pilot clinical trial where 5 AD patients will undergo DBS-PPN implantation and followed up for a1-year period.

7. ctv.veeva.com ctv.veeva.com/study/deep-brain-stimulation-of-the-pedunculopontine-nucleus-for-alzheimers-disease

Deep Brain Stimulation of the Pedunculopontine Nucleus for ... By stimulating the PPN, the study intervention aims to enhance gamma activity, potentially improving memory and cognition in AD patients.