Deep Brain Stimulation for Cognitive Deficits After Traumatic Brain Injury
Recruiting in Palo Alto (17 mi)
Overseen byNir Lipsman, MD PhD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Sunnybrook Health Sciences Centre
Disqualifiers: Epilepsy, Alzheimer's, Pregnancy, others
No Placebo Group
Trial Summary
What is the purpose of this trial?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.
Will I have to stop taking my current medications?
The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that participants should have evidence of failure to certain medications like donepezil and cholinesterase inhibitors, which might imply that these medications are not continued during the trial.
What data supports the effectiveness of the treatment Deep Brain Stimulation for cognitive deficits after traumatic brain injury?
Research shows that deep brain stimulation (DBS) can improve cognitive functions like processing speed in patients with moderate-to-severe traumatic brain injury. In a study, participants showed a 15% to 52% improvement in processing speed, indicating that DBS may help enhance executive control in these patients.
12345Is deep brain stimulation generally safe for humans?
Deep brain stimulation (DBS) is generally considered safe, but it can have complications. Studies show that overall complication rates can exceed 25%, with 4-6% of cases resulting in permanent neurological issues. It's important to understand these risks and how to minimize them as DBS is used for more conditions.
678910How is deep brain stimulation different from other treatments for cognitive deficits after traumatic brain injury?
Deep brain stimulation (DBS) is unique because it involves surgically implanting electrodes in specific brain areas to deliver electrical impulses, which can help reorganize brain networks and improve cognitive functions. Unlike other treatments, DBS directly targets brain regions involved in cognitive processing, potentially offering more precise and effective improvements for patients with traumatic brain injury.
14111213Eligibility Criteria
This trial is for individuals with memory and cognitive issues after a traumatic brain injury (TBI) who haven't improved with standard treatments. Specific eligibility criteria are not provided, but typically participants must meet certain health standards to undergo surgery.Inclusion Criteria
I have memory and thinking problems after a brain injury.
I am between 18 and 70 years old.
Patients with cognitive disorder not otherwise specified, dementia, or amnestic disorder due to TBI
+3 more
Exclusion Criteria
My kidney function is reduced.
Any contraindication to MRI scanning
Current suicidal or homicidal ideation
+4 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Surgery and Initial Treatment
Patients undergo surgery for deep brain stimulation with electrode implantation and initial stimulation settings
1 day
1 visit (in-person)
Post-Surgery Monitoring
Participants are monitored for treatment-related adverse events and initial response to DBS
8 weeks
Every 2 weeks (in-person)
Extended Monitoring
Continued monitoring of safety and effectiveness of DBS
6 months
Every 4 weeks (in-person)
Long-term Follow-up
Participants are monitored for long-term safety and effectiveness of DBS
2 years
Every 2 months (in-person)
Participant Groups
The study tests Deep Brain Stimulation (DBS), a surgical therapy that may improve memory and cognition in TBI patients. DBS has shown promise in preclinical TBI models and some Alzheimer's patients.
1Treatment groups
Experimental Treatment
Group I: Deep Brain StimulationExperimental Treatment1 Intervention
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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Sunnybrook Health Sciences CentreToronto, Canada
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Who Is Running the Clinical Trial?
Sunnybrook Health Sciences CentreLead Sponsor
References
Neurostimulation for Functional Recovery After Traumatic Brain Injury: Current Evidence and Future Directions for Invasive Surgical Approaches. [2023]We aim to provide a comprehensive review of the current scientific evidence supporting the use of invasive neurostimulation in the treatment of deficits associated with traumatic brain injury (TBI), as well as to identify future directions for research and highlight important questions that remain unaddressed. Neurostimulation is a treatment modality with expanding applications in modern medical practice. Targeted electrical stimulation of specific brain regions has been shown to increase synaptogenesis and enhance structural reorganization of neuronal networks. This underlying therapeutic effect might be of high value for patients suffering from TBI because it could modulate neuronal connectivity and function of areas that are partially or completely spared after injury. The current published literature exploring the application of invasive neurostimulation for the treatment of functional deficits associated with TBI is scarce but promising. Rodent models have shown that targeted stimulation of the hippocampus or connecting structures can result in significant cognitive recovery, while stimulation of the motor cortex and deep cerebellar nuclei is associated with motor improvements. Data from clinical studies are extremely limited; single-patient reports and case series found neurostimulation to be effective in relieving motor symptoms, improving visuospatial memory, and supporting emotional adjustment. Looking forward, it will be important to identify stimulation targets and paradigms that can maximize improvement over multiple functional domains. It will also be important to corroborate the observed behavioral improvements with histological, electrophysiological, and radiological evidence. Finally, the impact of biological variables such as sex and age on the treatment outcomes needs to be explored.
Clinical utility of brain stimulation modalities following traumatic brain injury: current evidence. [2022]Traumatic brain injury (TBI) remains the main cause of disability and a major public health problem worldwide. This review focuses on the neurophysiology of TBI, and the rationale and current state of evidence of clinical application of brain stimulation to promote TBI recovery, particularly on consciousness, cognitive function, motor impairments, and psychiatric conditions. We discuss the mechanisms of different brain stimulation techniques including major noninvasive and invasive stimulations. Thus far, most noninvasive brain stimulation interventions have been nontargeted and focused on the chronic phase of recovery after TBI. In the acute stages, there is limited available evidence of the efficacy and safety of brain stimulation to improve functional outcomes. Comparing the studies across different techniques, transcranial direct current stimulation is the intervention that currently has the higher number of properly designed clinical trials, though total number is still small. We recognize the need for larger studies with target neuroplasticity modulation to fully explore the benefits of brain stimulation to effect TBI recovery during different stages of recovery.
Impact of deep brain stimulation of the ventral anterior limb of the internal capsule on cognition in depression. [2022]Preliminary studies report no negative and a possible positive impact of deep brain stimulation (DBS) on cognition of patients with treatment-resistant depression (TRD). However, these studies neither controlled for practice effects nor compared active with sham stimulation.
Thalamic deep brain stimulation in traumatic brain injury: a phase 1, randomized feasibility study. [2023]Converging evidence indicates that impairments in executive function and information-processing speed limit quality of life and social reentry after moderate-to-severe traumatic brain injury (msTBI). These deficits reflect dysfunction of frontostriatal networks for which the central lateral (CL) nucleus of the thalamus is a critical node. The primary objective of this feasibility study was to test the safety and efficacy of deep brain stimulation within the CL and the associated medial dorsal tegmental (CL/DTTm) tract.Six participants with msTBI, who were between 3 and 18 years post-injury, underwent surgery with electrode placement guided by imaging and subject-specific biophysical modeling to predict activation of the CL/DTTm tract. The primary efficacy measure was improvement in executive control indexed by processing speed on part B of the trail-making test.All six participants were safely implanted. Five participants completed the study and one was withdrawn for protocol non-compliance. Processing speed on part B of the trail-making test improved 15% to 52% from baseline, exceeding the 10% benchmark for improvement in all five cases.CL/DTTm deep brain stimulation can be safely applied and may improve executive control in patients with msTBI who are in the chronic phase of recovery.ClinicalTrials.gov identifier: NCT02881151 .
Central thalamic deep-brain stimulation in the severely injured brain: rationale and proposed mechanisms of action. [2009]This review outlines the scientific rationale supporting the potential use of deep-brain electrical stimulation (DBS) in the central thalamus as a method to improve behavioral responsiveness following severe brain injury. Neurons within the central thalamus are selectively vulnerable to disconnection and dysfunction following severe brain injuries because of their unique geometry of cerebral connections. Because the central thalamus plays a key role in forebrain arousal regulation, impaired function of these cells has a broad impact. Prior clinical investigations, however, have targeted some components of the thalamus and related subcortical structures to improve behavioral responsiveness after severe brain injuries without providing evidence of sustained and clinically meaningful behavioral effects. Here important differences in conceptual framework, consideration of diagnostic categories for patient selection, and anticipated mechanisms of effect that distinguish earlier approaches and current studies are reviewed. As opposed to targeting chronically unresponsive patients, current efforts focus on identification of conscious patients with significant preservation of large-scale integrative cerebral networks. The potential mechanisms and limitations of this evolving strategy are discussed, including the need to develop frameworks to calibrate patient selection to potential clinical benefits, range of potential effect size, and other present unknowns.
Complications of deep brain stimulation in Parkinson's disease: a single-center experience of 517 consecutive cases. [2023]The number of deep brain stimulation (DBS) procedures is rapidly rising as well as the novel indications. Reporting adverse events related to surgery and to the hardware used is essential to define the risk-to-benefit ratio and develop novel strategies to improve it.
Safety considerations for deep brain stimulation: review and analysis. [2007]Deep brain stimulation has emerged rapidly as an effective therapy for movement disorders. Deep brain stimulation includes an implanted brain electrode and a pacemaker-like implanted pulse generator. The clinical application of deep brain stimulation proceeded in the absence of clear understandings of its mechanisms of action or extensive preclinical studies of safety and efficacy. Post mortem studies suggest that there is a loss of neurons in proximity to the active electrode, but the resulting lesions are not sufficient to treat the disorder and efficacy requires continued stimulation. Overall complication rates can exceed 25%, and permanent neurologic sequelae result in 4-6% of cases. As the application of deep brain stimulation expands, it is critical to understand the origin of adverse events and the delivery of nondamaging stimulation.
Towards unambiguous reporting of complications related to deep brain stimulation surgery: A retrospective single-center analysis and systematic review of the literature. [2019]To determine rates of adverse events (AEs) related to deep brain stimulation (DBS) surgery or implanted devices from a large series from a single institution. Sound comparisons with the literature require the definition of unambiguous categories, since there is no consensus on the reporting of such AEs.
Surgical and Hardware-Related Adverse Events of Deep Brain Stimulation: A Ten-Year Single-Center Experience. [2022]Although deep brain stimulation (DBS) is effective for treating a number of neurological and psychiatric indications, surgical and hardware-related adverse events (AEs) can occur that affect quality of life. This study aimed to give an overview of the nature and frequency of those AEs in our center and to describe the way they were managed. Furthermore, an attempt was made at identifying possible risk factors for AEs to inform possible future preventive measures.
Experience Reduces Surgical and Hardware-Related Complications of Deep Brain Stimulation Surgery: A Single-Center Study of 181 Patients Operated in Six Years. [2022]Deep brain stimulation (DBS) surgery has increasingly been performed for the treatment of movement disorders and is associated with a wide array of complications. We aimed to present our experience and discuss strategies to minimize adverse events in light of this contemporary series and others in the literature.
Transcranial direct current stimulation of the left prefrontal cortex improves attention in patients with traumatic brain injury: a pilot study. [2022]To determine whether a single session of anodal transcranial direct current stimulation to the left dorsolateral prefrontal cortex improves attention in patients with traumatic brain injury.
Making Waves in the Brain: What Are Oscillations, and Why Modulating Them Makes Sense for Brain Injury. [2020]Traumatic brain injury (TBI) can result in persistent cognitive, behavioral and emotional deficits. However, the vast majority of patients are not chronically hospitalized; rather they have to manage their disabilities once they are discharged to home. Promoting recovery to pre-injury level is important from a patient care as well as a societal perspective. Electrical neuromodulation is one approach that has shown promise in alleviating symptoms associated with neurological disorders such as in Parkinson's disease (PD) and epilepsy. Consistent with this perspective, both animal and clinical studies have revealed that TBI alters physiological oscillatory rhythms. More recently several studies demonstrated that low frequency stimulation improves cognitive outcome in models of TBI. Specifically, stimulation of the septohippocampal circuit in the theta frequency entrained oscillations and improved spatial learning following TBI. In order to evaluate the potential of electrical deep brain stimulation for clinical translation we review the basic neurophysiology of oscillations, their role in cognition and how they are changed post-TBI. Furthermore, we highlight several factors for future pre-clinical and clinical studies to consider, with the hope that it will promote a hypothesis driven approach to subsequent experimental designs and ultimately successful translation to improve outcome in patients with TBI.
Baseline delayed verbal recall predicts response to high definition transcranial direct current stimulation targeting the superior medial frontal cortex. [2023]Anodal high definition transcranial direct current stimulation (HD-tDCS) targeting the pre-supplementary motor area/dorsal anterior cingulate cortex (pre-SMA/dACC) has recently been shown to improve verbal retrieval deficits in veterans with chronic traumatic brain injury (TBI) (Motes et al., 2020), but predictors of treatment response are unclear. We hypothesized that baseline delayed verbal recall, a sensitive measure for post-TBI chronic cognitive decline, would predict therapeutic effects of HD-tDCS targeting the pre-SMA/dACC for verbal retrieval deficits. Standardized verbal retrieval measures were administered at baseline, immediately after and 8 weeks after treatment completion. We applied mixed generalized linear modeling as a post-hoc subgroup analysis to the verbal retrieval scores that showed significant improvement in Motes at el. (2020) to examine effects of active stimulation across the groups with baseline-intact delayed recall (N = 10) and baseline-impaired delayed recall (N = 8), compared to sham (N = 7). Individuals with impaired baseline delayed recall showed significant improvement (compared to baseline) in both category fluency and color-word inhibition/switch, while individuals with intact delayed recall showed significant improvement only in color-word inhibition/switch. Baseline delayed verbal recall may therefore be considered as a predictor for future electromodulation studies targeting frontal structures to treat TBI-related verbal deficits.