Deep Brain Stimulation for the Treatment of Traumatic Brain Injury

Jaimie M. Henderson

Status: Completed

Conditions: TBI (Traumatic Brain Injury)

Treatments: Device: Deep brain stimulation

Study type: Interventional

Funder types: Other

Identifiers

NCT02881151

37280

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 6 patients

Sex: All

Ages: 22 to 60 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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6 participants in 1 patient group

Treatment

Experimental group

Description:

Subjects will be treated with deep brain stimulation throughout the study, with the exception of a brief, 21 day blinded withdrawal phase that will be undertaken to assess for any possible therapeutic effect.

Treatment:

Device: Deep brain stimulation