deep brain stimulation for the treatment of traumatic brain injury

Conditions: TBI (Traumatic Brain Injury)

Summary: this study involves the treatment of cognitive impairment secondary to moderate to severe brain injury using central thalamic deep brain stimulation. although all patients will receive stimulation continuously through a surgically implanted pacemaker-like device, half of the patients will have the device deactivated during a blinded assessment phase. the device will be reactivated following this assessment and patients will have the option to continue stimulation in an open-label continuation.

this preliminary safety study evaluates the use of the medtronic activa pc+s system and medtronic nexus-e system for central thalamic deep brain stimulation (ct-dbs) in the treatment of cognitive impairment secondary to traumatic brain injury (tbi). it involves a neurosurgical procedure in which electrodes are implanted in the brain, connected to an implanted pacemaker-like device in the chest. the proposed study, if successful, will provide supporting evidence for the development of a novel therapeutic approach utilizing ct-dbs to improve these enduring cognitive impairments arising in persons with multi-focal structural brain injuries. this research will address the critical gap of the lack of any available treatments. ct-dbs targets well-defined neuronal populations within the central thalamus that have known anatomical and physiological specializations, which not only provide a key role in arousal regulation during cognitively-mediated behaviors, but also exhibit a particular vulnerability to dysfunction in the setting of multi-focal, non-selective brain injuries. our proposed study aims to support development of ct-dbs as a novel therapeutic avenue for accessing cognitive reserve in patients with acquired brain injuries. in the proposed feasibility study of 6 subjects at a single investigational site, we will test the safety of ct-dbs in the severe traumatic brain injury (stbi) population with gose 6-7 level recovery and collect data to establish the translation of preclinical studies into human application of ct-dbs.

Eligibility criteria:
inclusion criteria: * history of moderate to severe tbi based on worst gcs score within first 48 hours of injury (acceptable gcs range = 3-12) * age 22-60 * at least 24 months from date of onset * fluent in english and able to independently provide consent * rating of upper moderate disability to lower good recovery on the glasgow outcome scale-extended (gose) at time of enrollment (acceptable gose range 5-7) * failure to return to pre-injury level of vocational or educational function * either receiving no cns stimulants or other medications known to affect cognitive function, or on stable doses of these medications for the last three months exclusion criteria: * history of major developmental, neurologic, psychiatric or substance use disorder with evidence of disability prior to onset of tbi * major medical co-morbidities including: end stage renal failure, severe heart failure, coagulopathy, severe respiratory problems, severe liver failure, uncontrolled hypertension or other significant medical co morbidities * have had a documented seizure within 3 months of study screening (subjects may re-screen if seizure free after initial screen failure) * malignancy with \< 5 years life expectancy * untreated / uncontrolled (severe at the time of enrollment) depression or other psychiatric disorder * women of childbearing age who do not regularly use an accepted contraceptive method * inability to stop anticoagulation therapy or platelet anti-aggregation therapy before, during and after surgery * previous dbs or other brain implants * previous ablative intracranial surgery * implantable hardware not compatible with mri * condition requiring diathermy after dbs implantation * hardware, lesions or other factors limiting placement of electrodes in optimal target location in the judgment of the operating surgeon * concurrent enrollment in any other clinical trial * any condition or finding that, in the judgment of the pi, significantly increases risk or significantly reduces the likelihood of benefit from dbs

Keywords: deep brain stimulation dbs central thalamus tbi traumatic brain injury