DBS for Cognitive Deficits After Traumatic Brain Injury

NCT06818864 | Recruiting Phase 1

• 1 other identifier: 5762
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with memory and cognitive deficits following TBI that do not respond to conventional treatments experience a decrease in quality of life. Despite advances in neuroimaging, genetics, pharmacology and psychosocial interventions in the last half century, little progress has been made in altering the natural history of the condition or its outcome. This study would explore whether a surgical therapy is safe and potentially effective in patients who develop refractory memory and cognitive deficits following TBI. Preclinical studies suggest that DBS may improve memory deficits in TBI models. Moreover, DBS delivered to the fornix has shown promising clinical results in patients with Alzheimer's disease. The main mechanism for the improvements induced by DBS in memory tests is the development of multiple forms of plasticity.

Conditions

TBI Traumatic Brain Injury

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by SAFTEE

  The primary objective is to establish the safety of deep brain stimulation in a patient population with TBI and cognitive deficits using the Systematic Assessment for Treatment Emergent Events (SAFTEE)

  Every 2 weeks until the 8 weeks mark, every 4 weeks until 6 month mark and every two months until the 2 year mark

Study Arms (1)

Deep Brain Stimulation

EXPERIMENTAL

Patients will arrive on the morning of surgery to the medical imaging department of the Sunnybrook Hospital. They will have a stereotactic frame attached directly to their skull, after infiltration with local anesthesia. The frame allows precise coordinates to be acquired so that deep brain structures can be targeted with implanted electrodes. The patient will then undergo a CT scan with the frame in place, followed by transport directly to the operating room. The anesthesia team will insert an intravenous line and may use gentle sedation to relax the patient prior to and during the operation, as they will remain awake during the first stage of the operation. In the operating room the patient's head, via the frame, will be attached to the operating room table, and their scalp infiltrated with additional local anesthetic. A skin incision will be made and two burr holeswith approximately 1.4cm in diameter drilled through the skull. A small electrode will identify the optimal spot for el

Device: Deep Brain Stimulation

Interventions

Deep Brain Stimulation DEVICE

Patients will arrive on the morning of surgery to the medical imaging department of the Sunnybrook Hospital. They will have a stereotactic frame attached directly to their skull, after infiltration with local anesthesia. The frame allows precise coordinates to be acquired so that deep brain structures can be targeted with implanted electrodes. The patient will then undergo a CT scan with the frame in place, followed by transport directly to the operating room. The anesthesia team will insert an intravenous line and may use gentle sedation to relax the patient prior to and during the operation, as they will remain awake during the first stage of the operation. In the operating room the patient's head, via the frame, will be attached to the operating room table, and their scalp infiltrated with additional local anesthetic. A skin incision will be made and two burr holeswith approximately 1.4cm in diameter drilled through the skull. A small electrode will identify the optimal spot for ele

Deep Brain Stimulation

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female or male patients between age 18-70.
• Diagnosis of memory and cognitive deficits in patients who suffered TBI will be defined according to the Diagnostic and Statistical Manual 5th edition (DSM-5).
• Patients with cognitive disorder not otherwise specified, dementia, or amnestic disorder due to TBI will be considered.
• Performance at least 1.5 standard deviations below the estimated premorbid intelligence (assessed by the American National Adult Reading Test) on memory tests (assessed by the California Verbal Learning Test; CVLT).
• History of TBI for at least 1 year, preferably with evidence of failure to donepezil, cholinesterase inhibitors and cognitive therapy.
• Ability to provide informed consent and comply with all testing, follow-ups and study appointments.

You may not qualify if:

• Active neurologic disease, such as epilepsy or Alzheimer's disease.
• Any contraindication to magnetic resonance imaging (MRI) scanning.
• Presence of clinical and/or neurological conditions that may significantly increase the risk of the surgical procedure
• Current suicidal or homicidal ideation.
• Active neurologic disease, such as epilepsy.
• Pregnancy.
• Likely to relocate or move during the study's one year duration
• Patients with renal dysfunction (GFR\<60)

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead

Study Sites (1)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N3M5, Canada

RECRUITING

MeSH Terms

Conditions

Brain Injuries, Traumatic

Interventions

Deep Brain Stimulation

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Surgical Procedures, Operative

Study Officials

• Nir Lipsman, MD PhD

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anusha Baskaran, PhD

CONTACT

416-480-6100; anusha.baskaran@sunnybrook.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Neurosurgeon

Model Details: This is a phase I, non-blinded, non-randomized, open-label, pilot trial for safety and efficacy of deep brain stimulation for TBI. Patients who meet inclusion and exclusion criteria will be identified and recruited from the practices of psychiatrists and neurologists who specialize in treating patients with TBI who develop cognitive deficits. The study will proceed according to the schedule laid out below. Both patients and treating team will be aware of treatment parameters at all times. Up to ten (10) subjects will be enrolled. Study duration for each patient will be of one (1) year. Previous phase I trials of DBS in psychiatric populations have utilized 5-6 subjects per surgical target. Such a number has been sufficient to demonstrate initial safety, feasibility and provide preliminary data on clinical effectiveness.

Study Record Dates

• First Submitted: November 20, 2024
• First Posted: February 11, 2025
• Study Start: November 1, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: February 11, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)