Deep Brain Stimulation for the Treatment of Traumatic Brain Injury

• ClinicalTrials.gov Identifier: NCT02881151
• Recruitment Status: Active, not recruiting
• First Posted: August 26, 2016
• Last Update Posted: June 15, 2021
• Sponsor: Jaimie M. Henderson
• Collaborators: Weill Medical College of Cornell University; University of Utah; Harvard Medical School; The Cleveland Clinic
• Information provided by (Responsible Party): Jaimie M. Henderson, Stanford University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
TBI (Traumatic Brain Injury)	Device: Deep brain stimulation	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: CT-DBS for Traumatic Brain Injury Using the Medtronic Activa PC+S System
• Actual Study Start Date: April 20, 2017
• Estimated Primary Completion Date: November 30, 2021
• Estimated Study Completion Date: August 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment; 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.	Device: Deep brain stimulation; Delivery of continuous, low-voltage electrical pulses to deep portions of the brain via an implantable pacemaker-like device.; Other Names: DBS; CT-DBS; Central Thalamic DBS

Outcome Measures

Primary Outcome Measures :

1. Trail Making Test [ Time Frame: 1 year ]
   The Trail Making Test is a measure of attention, speed and mental flexibility

Secondary Outcome Measures :

1. Measures of cognition [ Time Frame: 1 year ]
   Assessed using the Ruff 2 and 7
2. Physical symptoms [ Time Frame: 1 year ]
   Assessed using the Rivermead Post-Concussion Symptom Questionnaire
3. Psychological health [ Time Frame: 1 year ]
   Assessed using the Patient Health Questionnaire - 9, Columbia Suicide Severity Rating Scale
4. Traumatic Brain Injury Quality of Life [ Time Frame: 1 year ]
   Assessed using the Traumatic Brain Injury Quality of Life scale
5. Measure of global function [ Time Frame: 1 year ]
   Assessed using the Glasgow Outcome Scale - Extended

Eligibility Criteria

• Ages Eligible for Study: 22 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)
• 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

Contacts and Locations

Locations

United States, California

Stanford Health Care

Stanford, California, United States, 94305

Sponsors and Collaborators

Jaimie M. Henderson

Weill Medical College of Cornell University

University of Utah

Harvard Medical School

The Cleveland Clinic

Investigators

• Study Director: Jaimie M Henderson, MD; Stanford University

More Information

• Responsible Party: Jaimie M. Henderson, John and Jene Blume - Robert and Ruth Halperin Professor, Stanford University
• ClinicalTrials.gov Identifier: NCT02881151
• Other Study ID Numbers: 37280
• First Posted: August 26, 2016
• Last Update Posted: June 15, 2021
• Last Verified: June 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

Keywords provided by Jaimie M. Henderson, Stanford University:

Deep brain stimulation; DBS; Central thalamus; TBI; Traumatic brain injury

Additional relevant MeSH terms:

Brain Injuries; Brain Injuries, Traumatic; Wounds and Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System