Recruiting

Deep Brain Stimulation

Sponsor:

University Health Network, Toronto

Code:

NCT06936124

Conditions

Alzheimer Disease

Eligibility Criteria

Sex: All

Age: 60+

Healthy Volunteers: Accepted

Interventions

Deep Brain Stimulation of the Pedunculopontine Nucleus

Study Details

Brief summary:

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.

Conditions

Alzheimer Disease

Study ID

NCT06936124

Start date

May, 2025

Status verified date

Apr, 2025

Completion date

Nov, 2028

Anticipated

Primary completion date

Nov, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 60+

Healthy Volunteers: Accepted

Inclusion Criteria:

  • Adults over 60 years old.
  • Diagnosis of Alzheimer's Disease: Satisfied the diagnostic criteria of the National Institute of Aging - Alzheimer's Association criteria for probable AD.
  • Clinical dementia rating scale global score of ≤ 1.
  • Not taking an acetylcholinesterase inhibitor and/or memantine, or taking a stable dose for at least six months.
  • Fluent in English.
  • Caregiver available to participate in the study.

Exclusion Criteria:

  • Pre-existing structural brain abnormalities (e.g., significant white matter disease, tumor, infarction, or intracranial hematoma).
  • Other neurologic or psychiatric diagnoses, or medical comorbidities that would preclude patients from undergoing surgery.
  • Non-fluent in English (it will be very difficult to conduct standard cognitive tests in English on non-fluent English speakers. In addition, language barrier is significant hurdle in providing standard care with communication and cognition being a main outcome measure).

Study Design

Enrollment

6 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Deep Brain Stimulation of the Pedunculopontine Nucleus

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.

Interventions

Deep Brain Stimulation of the Pedunculopontine Nucleus

The DBS implantation procedure targeting the PPN involves a neurosurgical operation performed under general anesthesia. During the procedure, thin electrodes are implanted in the PPN with the aid of advanced pre-operative imaging (MRI and CT scan) to confirm precise targeting. This device generates and transmits electrical impulses to the PPN, which can be adjusted to optimize therapeutic outcomes.

Primary outcome measure

  • Intervention Feasibility - Recruitment Rates [ Time Frame: Study Initiation to End of Study Enrolment Period (36 month period) ]
  • Intervention Feasibility - Adherence to Study Protocol [ Time Frame: Study Initiation to Final Participant Study Completion (3 years) ]
  • Intervention Feasibility - Attrition Rates [ Time Frame: Study Initiation to Final Participant Study Completion by (3 years) ]
  • Intervention Feasibility - Participant Evaluation of Intervention [ Time Frame: Participants will complete the exit interview at the final follow-up visit (month 12). ]
  • Intervention Safety - Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Assessed at DBS implantation (Month 0) and at regular follow-up visits 1-month, 3-months, 6-months, 9-months, and 12-months post-DBS surgery. ]
  • Intervention Safety - AE Severity [ Time Frame: Assessed at DBS implantation (Month 0) and at regular follow-up visits 1-month, 3-months, 6-months, 9-months, and 12-months post-DBS surgery. ]
  • Intervention Safety - AE Relationship to Study Intervention [ Time Frame: Assessed at DBS implantation (Month 0) and at regular follow-up visits 1-month, 3-months, 6-months, 9-months, and 12-months post-DBS surgery. ]
  • Intervention Safety - AE Outcome [ Time Frame: Assessed at final follow-up visit 12-months post-DBS surgery, or at the last time of observation. ]

Central Contacts and Locations

Central contacts

Delaney Sharp

416-918-4059delaney.sharp2@uhn.ca

Steven Carcone

steven.carcone@uhn.ca

Locations

Toronto Western Hospital

Recruiting

Toronto, Ontario, Canada, M5T 2S8

Contacts

Delaney E Sharp

416-918-4059delaney.sharp2@uhn.ca

Steven Carcone

steven.carcone@uhn.ca

Principal Investigator:

Taufik A. Valiante, MD PhD FRCS

More Information

Sponsor

University Health Network, Toronto

Last update posted

May 1, 2025

Last verified

Apr, 2025

Keywords

  • Alzheimer Disease
  • Deep Brain Stimulation
  • Pedunculopontine Nucleus
  • DBS-PPN
  • DBS

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University Health Network, Toronto on 2025-05-01.