Clinical trial NCT02881151: Deep Brain Stimulation for the Treatment of Traumatic Brain Injury
Official title: CT-DBS for Traumatic Brain Injury Using the Medtronic Activa PC+S System
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: TBI (Traumatic Brain Injury)
Keywords: Deep brain stimulation
DBS
Central thalamus
TBI
Traumatic brain injury
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: Weill Medical College of Cornell University
name: University of Utah
name: Harvard Medical School (HMS and HSDM)
name: The Cleveland Clinic
First posted: 2016-08-26
Enrollment: 6
Sex: ALL
Minimum age (years): 22
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

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

Primary outcomes:
measure: Percent Change in Trail Making Test Part B Time to Completion
timeFrame: Pre-surgery baseline to treatment phase end (up to 197 days)
Secondary outcomes:
measure: Percent Change in Trail Making Test Part A Time to Completion
timeFrame: Pre-surgery baseline to treatment phase end (up to 197 days)
measure: Percent Change in Traumatic Brain Injury Quality of Life - Executive Function Short Form (TBI-QOL) Scale Score
timeFrame: Pre-surgery baseline to treatment phase end (up to 197 days)
measure: Percent Change Traumatic Brain Injury Quality of Life - Attention/Concentration Short Form Scale Score
timeFrame: Pre-surgery baseline to treatment phase end (up to 197 days)
measure: Percent Change in Traumatic Brain Injury Quality of Life - Fatigue Short Form Scale Score
timeFrame: Pre-surgery baseline to treatment phase end (up to 197 days)
measure: Percent Change in Rivermead Post-Concussion Symptom Questionnaire Scale Score
timeFrame: Pre-surgery baseline to treatment phase end (up to 197 days)
measure: Percent Change in Ruff 2 and 7 Automatic Detection Speed Score
timeFrame: Pre-surgery baseline to treatment phase end (up to 197 days)
measure: Percent Change in Ruff 2 and 7 Automatic Detection Accuracy Score
timeFrame: Pre-surgery baseline to treatment phase end (up to 197 days)
measure: Percent Change in Ruff 2 and 7 Controlled Search Speed Score
timeFrame: Pre-surgery baseline to treatment phase end (up to 197 days)
measure: Percent Change in Ruff 2 and 7 Controlled Search Accuracy Score
timeFrame: Pre-surgery baseline to treatment phase end (up to 197 days)
measure: Percent Change in Patient Health Questionnaire - 9 Scale Score.
timeFrame: Pre-surgery baseline to treatment phase end (up to 197 days)
measure: Number of Participants With ≥1 Point Increase in Glasgow Outcome Scale - Extended Scale Score
timeFrame: Pre-surgery baseline to treatment phase end (up to 197 days)
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford Health Care
state: California
Study officials:
affiliation: Stanford University
name: Jaimie M Henderson, MD
role: STUDY_DIRECTOR
References:
citation: Wilson JT, Pettigrew LE, Teasdale GM. Structured interviews for the Glasgow Outcome Scale and the extended Glasgow Outcome Scale: guidelines for their use. J Neurotrauma. 1998 Aug;15(8):573-85. doi: 10.1089/neu.1998.15.573.