跳至主要内容
临床试验/NCT06818864
NCT06818864招募中1 期

Deep Brain Stimulation (DBS) for the Treatment of Cognitive Deficits After Traumatic Brain Injury (TBI): Pilot Trial

Sunnybrook Health Sciences Centre2 个研究点 分布在 1 个国家目标入组 10 人开始时间: 2024年11月1日最近更新:

试验速览

阶段
1 期
状态
招募中
入组人数
10
试验地点
2
主要终点
Number of participants with treatment-related adverse events as assessed by SAFTEE

研究概览

简要总结

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.

详细描述

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.

研究设计

研究类型
Interventional
分配方式
Na
干预模型
Single Group
主要目的
Treatment
盲法
None

入排标准

年龄范围
18 Years 至 70 Years(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • Female or male patients between age 18-
  • 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.

排除标准

  • 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.
  • Likely to relocate or move during the study's one year duration
  • Patients with renal dysfunction (GFR<60)

结局指标

主要结局

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

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

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)

次要结局

未报告次要终点

研究者

申办方类型
Other
责任方
Principal Investigator
主要研究者

Dr. Nir Lipsman

Neurosurgeon

Sunnybrook Health Sciences Centre

研究点 (2)

Loading locations...

相似试验