Deep Brain Stimulation for the Treatment of Traumatic Brain Injury

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.

Inclusion Criteria:

- History of moderate to severe TBI based on worst GCS score within first 48 hours of
injury (acceptable GCS range = 3-9)

- Age 22-55

- 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)

- Performance ≥ 2 SD's below the demographically-corrected mean on at least one
attention, memory or executive function measure at baseline

- 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