Vagus Nerve Stimulation to Augment Recovery From Minimally Conscious or Persistently Vegetative States After Traumatic Brain Injury

NCT01260090 | Withdrawn Phase 2

• 1 other identifier: B7301P
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Traumatic brain injury has a high morbidity and mortality in both civilian and military populations. Blast and other mechanisms of traumatic brain injury damage the brain by causing neurons to disconnect and atrophy. Such traumatic axonal injury can lead to persistently vegetative and minimally conscious states, for which extremely limited treatment options exist, including physical, occupational, speech and cognitive therapies. More than 50,000 patients have received vagus nerve stimulation for epilepsy and depression. In addition to decreased seizure frequency and severity, patients report enhanced mood, reduced daytime sleepiness independent of seizure control, increased slow wave sleep, and improved cognition, memory, and quality of life. The purpose of this study is to demonstrate objective improvement in clinical outcome by placement of a vagus nerve stimulator in patients who are recovering from severe traumatic brain injury. Our hypothesis is that stimulation of the vagus nerve results in increased cerebral blood flow and metabolism in the forebrain, thalamus and reticular formation, which promotes arousal and improved consciousness, thereby improving outcome after traumatic brain injury resulting in minimally conscious or persistent vegetative states. If this study demonstrates that vagus nerve stimulation can safely and positively impact outcome, then a larger randomized prospective crossover trial will be proposed. The investigators will achieve this objective by evaluating whether vagus nerve stimulation impacts clinical recovery from minimally conscious or persistent vegetative states caused by traumatic brain injury as assessed by the FIM™ instrument and Functional Assessment Measure (FIM+FAM) as well as the JFK Coma Recovery Scale Score. The investigators will also evaluate whether vagus nerve stimulation alters resting and activational functional MRI. Twelve patients will be enrolled in this initial crossover pilot study. These patients will have sustained a severe traumatic brain injury (Disability Rating Scale score of 22 to 29) more than twelve months from starting the study, and have no other concurrent active severe medical problems. Baseline EEG and magnetic resonance imaging (MRI) will be performed prior to left vagus nerve stimulation implantation. Patients will be randomized to alternating three month periods with the device on or off. Outcomes will be assessed at three month intervals with the FIM™ instrument and Functional Assessment Measure (FIM+FAM) and JFK Coma Recovery Scale by a neuropsychologist blinded to the status of the device. Outcomes will also be assessed using quantitative eye movement tracking and functional magnetic resonance imaging. Patients will cross over every 3 months and be followed for at least 18 months.

Conditions

Minimally Conscious States Due to Traumatic Brain Injury; Persistently Vegetative States Due to Traumatic Brain Injury

Keywords

Minimally conscious states; Persistently vegetative states; Traumatic brain injury

Outcome Measures

Primary Outcomes (1)

• JFK Coma Recovery Scale

  every 3 months for 18 months

Secondary Outcomes (2)

• FIM plus FAM

  every 3 months for 18 months

• functional MRI

  every 3 months for 18 months

Study Arms (2)

Vagus Nerve Stimulation

EXPERIMENTAL

Name of the Device: We will use the PMA approved version of the NCP System, including the NCP Generator (model 103), NCP Programming Wand (model 201), NCP Programming Software (model 250v7.1), NCP Lead (model 304), NCP Tunneling Tool (model 402) and the Patient Magnet (model 220). FDA Facility Registration Number: 1644487

Device: Vagus nerve stimulation;

No Stimulation

SHAM COMPARATOR

Device: No stimulation

Interventions

Vagus nerve stimulation; DEVICE

Name of the Device: We will use the PMA approved version of the NCP System, including the NCP Generator (model 103), NCP Programming Wand (model 201), NCP Programming Software (model 250v7.1), NCP Lead (model 304), NCP Tunneling Tool (model 402) and the Patient Magnet (model 220). FDA Facility Registration Number: 1644487

Vagus Nerve Stimulation

No stimulation DEVICE

Vagus nerve stimulation

No Stimulation

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age between 18 and 60
• greater than 12 months from a moderate to severe traumatic brain injury
• Disability Rating Scale score of 18 to 29
• with or without concurrent seizure activity
• Eligible for care in the VA system

You may not qualify if:

• Anoxic mechanism of brain injury (eg prolonged arrest)
• Untreated hydrocephalus
• Elevated intracranial pressure
• Systemic issues precluding surgery or 18 months survival
• Traumatic injuries precluding surgery or 18 months survival
• Retained shrapnel or other metal contraindicating MRI
• Prior vagotomy
• Sleep apnea
• Myocardial infarction, arrhythmia
• History of cardiac conduction abnormality
• Pregnancy or intent to become pregnant
• Pre-existing CNS disease

Sponsors & Collaborators

• VA New York Harbor Healthcare System: lead

Study Sites (1)

Manhattan Va NYHHCS

New York, New York, 10010, United States

Location

MeSH Terms

Conditions

Persistent Vegetative State; Brain Injuries, Traumatic

Interventions

Vagus Nerve Stimulation

Condition Hierarchy (Ancestors)

Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Unconsciousness; Consciousness Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Brain Injuries; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Neurosurgeon

Study Record Dates

• First Submitted: December 14, 2010
• First Posted: December 15, 2010
• Study Start: January 1, 2011
• Primary Completion: July 1, 2013
• Study Completion: October 1, 2013
• Last Updated: April 27, 2023

Record last verified: 2023-04

Locations

US (1)