Deep Brain Stimulation for the Treatment of Traumatic Brain Injury

NCT ID: NCT02881151

Last Updated: 2022-12-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-20
• Study Completion Date: 2022-05-04

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.

Conditions

TBI (Traumatic Brain Injury)

Keywords

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Deep brain stimulation

Intervention Type: DEVICE

Delivery of continuous, low-voltage electrical pulses to deep portions of the brain via an implantable pacemaker-like device.

Interventions

Deep brain stimulation

Delivery of continuous, low-voltage electrical pulses to deep portions of the brain via an implantable pacemaker-like device.

Intervention Type: DEVICE

Other Intervention Names

DBS; CT-DBS; Central Thalamic 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

• Minimum Eligible Age: 22 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Weill Medical College of Cornell University

OTHER

Sponsor Role: collaborator

University of Utah

OTHER

Sponsor Role: collaborator

Harvard Medical School (HMS and HSDM)

OTHER

Sponsor Role: collaborator

The Cleveland Clinic

OTHER

Sponsor Role: collaborator

Jaimie M. Henderson

OTHER

Sponsor Role: lead

Responsible Party

Jaimie M. Henderson

John and Jene Blume - Robert and Ruth Halperin Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jaimie M Henderson, MD

Role: STUDY_DIRECTOR

Stanford University

Locations

Stanford Health Care

Stanford, California, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 9726257 (View on PubMed)

Schiff ND, Giacino JT, Butson CR, Choi EY, Baker JL, O'Sullivan KP, Janson AP, Bergin M, Bronte-Stewart HM, Chua J, DeGeorge L, Dikmen S, Fogarty A, Gerber LM, Krel M, Maldonado J, Radovan M, Shah SA, Su J, Temkin N, Tourdias T, Victor JD, Waters A, Kolakowsky-Hayner SA, Fins JJ, Machado AG, Rutt BK, Henderson JM. Thalamic deep brain stimulation in traumatic brain injury: a phase 1, randomized feasibility study. Nat Med. 2023 Dec;29(12):3162-3174. doi: 10.1038/s41591-023-02638-4. Epub 2023 Dec 4.

Reference Type: DERIVED

PMID: 38049620 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

37280

Identifier Type: -

Identifier Source: org_study_id