DBS for Cognitive Deficits After Traumatic Brain Injury

NCT ID: NCT06818864

Last Updated: 2025-02-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-11-01
• Study Completion Date: 2026-11-01

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.

Detailed Description

Traumatic brain injury (TBI) remains a significant public health issue with an incidence of 55-70 million individuals worldwide. In Canada, TBI leads to 23,000 hospitalizations per year with 8% of individuals succumbing to their injuries. In addition to neurologic deficits, TBI may lead to a spectrum of long-term impairments, including cognitive difficulties (e.g., attention, memory), neurologic symptoms (e.g., headaches, dizziness) and neuropsychiatric sequalae (e.g. anxiety, post-traumatic stress disorder). TBI has also been associated with neurodegenerative disorders, such as chronic traumatic encephalopathy and the development of Alzheimer's-type pathology.

Cognitive rehabilitation programs are important tools for clinical recovery of TBI patients, improving functional outcomes and the quality of life. Some of these strategies are based on the development of compensatory strategies and neuroplasticity. Due to the short liver nature of some of the associated improvements and neuroplastic phenomena, stimulating specific neuronal circuits has been proposed.

To date, class I evidence suggests that cognitive improvement following rehabilitation is more effective than sham treatment. In general, however, cognitive rehabilitation therapy is effective in 80-90% of patients. This means that 10-20% of patients remain severely disabled despite treatment.

Deep Brain Stimulation is a neurosurgical tool that has been widely used for over twenty years. Most of the experience with DBS comes from the movement disorder literature where significant success has been had with the management of disabling Parkinson's Disease (PD) and dystonia. Owing to similar underlying circuitry, and the frequent co-occurrence of psychiatric and neurologic conditions, DBS has been suggested for the management of treatment resistant neuropsychiatric conditions, with some promising results.

To date, clinical studies using DBS following TBI are largely comprised of case reports and small case series. The most common application of invasive neurostimulation has been for the treatment of post-TBI dystonic symptoms and tremor. In addition to motor improvement, Miller et al reported a series of 4 patients who presented an improvement in visuospatial memory following fornix burst stimulation. Zhou et al reported that DBS delivered to the anterior limb of internal capsule and the region of the nucleus accumbens improved post-TBI auditory hallucinations, mood changes, and insomnia in a single female patient. Kuhn et al. reported a patient who had a substantial reduction in post- TBI self-mutilating behavior following posterior hypothalamus stimulation. An improvement in emotional adjustment and functional independence was reported in 4 TBI patients treated with nucleus accumbens DBS.Aside from the cognitive, psychiatric and mood improvements described above, DBS has also been investigated for the recovery of consciousness in patients in minimally conscious states. Out of 10 patients reported in the literature, an improvement was observed in 8 individuals using coma scales and related metrics.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Deep Brain Stimulation

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

Group Type: EXPERIMENTAL

Deep Brain Stimulation

Intervention Type: 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

Interventions

Deep Brain Stimulation

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

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. Female or male patients between age 18-70.

2. 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).

3. Patients with cognitive disorder not otherwise specified, dementia, or amnestic disorder due to TBI will be considered.

4. 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).

5. History of TBI for at least 1 year, preferably with evidence of failure to donepezil, cholinesterase inhibitors and cognitive therapy.

6. Ability to provide informed consent and comply with all testing, follow-ups and study appointments.

Exclusion Criteria

1. Active neurologic disease, such as epilepsy or Alzheimer's disease.

2. Any contraindication to magnetic resonance imaging (MRI) scanning.

3. Presence of clinical and/or neurological conditions that may significantly increase the risk of the surgical procedure

4. Current suicidal or homicidal ideation.

5. Active neurologic disease, such as epilepsy.

6. Pregnancy.

7. Likely to relocate or move during the study's one year duration

8. Patients with renal dysfunction (GFR<60)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sunnybrook Health Sciences Centre

OTHER

Sponsor Role: lead

Responsible Party

Dr. Nir Lipsman

Neurosurgeon

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Nir Lipsman, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Sunnybrook Health Sciences Centre

Locations

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Anusha Baskaran, PhD

Role: CONTACT

anusha.baskaran@sunnybrook.ca

416-480-6100 ext. 61650

Facility Contacts

Anusha Baskaran, PhD

Role: primary

416-480-6100 ext. 61650

Other Identifiers

5762

Identifier Type: -

Identifier Source: org_study_id