Paired Vagus Nerve Stimulation in Mobilization of Patients With Prolonged Disorders of Consciousness

Use of Paired Vagus Nerve Stimulation in Mobilization of Patients With Prolonged Disorders of Consciousness: A Pilot Feasibility Study

Prolonged disorders of consciousness (pDOC) are defined as DOC lasting >1 year post injury for patients with Traumatic Brain Injury (TBI) and >3 months post injury for patients with non-TBI and at present there are limited treatments that reliably lead to enhanced prognosis. The rehabilitation process throughout the continuum of care for patients with pDOC necessitates restorative strategies to facilitate arousal and functional recovery and coordinated medical management. Rehabilitation interventions for patients with DOC and pDOC have evolved in the past decade, with an emerging body of evidence highlighting the benefits of rehabilitation intervention even in the acute. While there is data to support the individual utility of these modalities, no work to date has investigated the benefits of pairing transauricular vagus nerve stimulation (taVNS) and robotic tilt table mobilization (RTTM) to maximize functional recovery in patients with pDOC. This study will report on the safety, feasibility, and preliminary short- and long-term outcomes of RTTM with simultaneously paired Transcutaneous auricular vagus nerve stimulation (taVNS) for Severe Acquired Brain Injury (SABI) patients with pDOC . Fifteen (15) participants will be recruited and complete a 12-week rehabilitation protocol using paired taVNS and RTTM. Once participants have been screened and enrolled in the study, they will complete three study phases: T1: a baseline observation of standard of care T2, intervention, and T3 longitudinal follow up.

Study Overview

• Status: Recruiting
• Conditions: Brain Injury; Consciousness Disorders; Altered Level of Consciousness
• Intervention / Treatment: Device: Transcutaneous vagus nerve stimulation (taVNS); Device: Physical therapy using Hocoma; Behavioral: Standard of Care

Detailed Description

T1: At baseline prior to initiating Phase 1, participants will be assessed using Coma Recovery Scale-Revised (CRS-R), Glasgow Coma Scale (GCS), and Glasgow Outcomes Scale- Extended (GOSE). Following this baseline assessment, participants will continue with 4 weeks of their current standard of care. During Phase 1, no study interventions will be implemented. At completion of T1, the CRS-R, GCS, and GOSE will be reassessed. Following Phase 1,

T2a: will be initiated immediately thereby and will entail a 4-week mobilization only phase. Participants will complete 8 sessions of physical therapy over 4 weeks, receiving progressive verticalization and mobilization using a robotic tilt table with robotic stepping (Erigo; Hocoma).

T2b: Immediately after 4 week mobilization only period, participants will complete 8 sessions of physical therapy over 4 weeks, receiving the paired taVNS + RTTM intervention. Upon completion of phase 2b, participants will be reassessed with CRS-R, GCS, and GOSE.

T3: Following the intervention period, participants will complete three additional study visits for assessment at 3-, 6-, and 12-months post intervention using the CRS-R, GOSE, and GCS. Across all study phases, secondary healthcare utilization, including re-admission rates, number of physicians follow up visits and emergency room visits, will be captured from the patient electronic medical record (EMR) and reported.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jenna Tosto-Mancuso, PT, DPT, NCS; Phone Number: 212-241-8454; Email: ARCClinic@mountsinai.org

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Abilities Research Center, Icahn School of Medicine at Mount Sinai
      • Contact: Jenna Tosto Mancuso; Phone Number: 212-241-8454
      • Principal Investigator: Jenna Tosto-Mancuso

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with a diagnosis of pDOC (includes coma, VS/UWS, MCS, MCS +, MCS-) as defined as disorder of consciousness (DOC) greater than 3 months post onset
• Patients deemed medically safe to participate in physical therapy (PT) as evaluated by the study physicians.

Exclusion Criteria:

• Patients who have emerged from MCS (CRS-R score 6 on Motor Function scale and/or 2 on Communication Scale).
• Patients medically unsafe for participation in PT as indicated by one of the study physicians (including but not limited to those receiving intravenous sedation, those with integumentary breakdown or known pressure injuries, those with cardiovascular or cerebrovascular conditions precluding initiation of physical therapy [ie uncontrolled intracranial pressure, severe symptomatic orthostatic hypotension, etc.).
• Patients with DOC less than 3 months post onset will also be excluded.

• Patients who do not meet technical requirements of the RTTM device will be excluded

  • weighing greater than 135 kg
  • length of legs below 75 cm or above 100 cm,
  • fixed contractures of lower extremity including hip, knee, ankle, or foot).
• Does not have an identified care partner or legally authorized representative to consent to participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Patients with Prolonged Disorders of Consciousness (pDOC); Patients with pDOC receiving paired transauricular vagus nerve stimulation (taVNS) and robotic tilt table mobilization (RTTM) to maximize functional recovery,

Device: Transcutaneous vagus nerve stimulation (taVNS); A non-invasive nerve stimulator that stimulates the vagus nerve through the ear.; Device: Physical therapy using Hocoma; Progressive verticalization and mobilization using a robotic tilt table with robotic stepping (Erigo, Hocoma); Behavioral: Standard of Care; Standard of care with no study interventions. This will include observation of whatever rehabilitation or medical care the patient is currently receiving.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Coma Recovery Scale-Revised (CRS-R)	The CRS-R is a standardized neurobehavioral rating scale used to monitor recovery of consciousness in persons with severe traumatic brain injury. Six subscales on the CRS-R are summed to provide the total score: auditory function (0-4), visual function (0-5), motor function (0-6), promotor/verbal function (0-3), communication (0-2) and arousal (0-3). Total scores on the CRS-R range from 0 to 23 with high scores generally indicating greater recovery	Baseline, 4 weeks (T1), 8 weeks (T2), and 3-,6-,12-months post intervention (T3)
Glasgow Coma Scale (GCS)	The Glasgow Coma Scale (GCS) is a reliable and objective way of recording the initial and subsequent level of consciousness in a person after a brain injury. The range of total GCS score is 3 to15 where a higher GCS score represents a better outcome. The scores of subscales are summed to determine the total score*. A GCS score of 13-15 is considered Mild impairment of consciousness; a GCS score of 9-12 is considered Moderate impairment of consciousness; and a GCS score of 3-8 is considered Severe. *Subscales: Eyes Response: Spontaneous=4; To sound=3; To Pressure=2; None=1; Not tested; Verbal Response: Oriented=5; Confused=4; Words=3; Sounds=2; None=1; Not tested; Motor Response: Obeys Commands=6; Localizes=5; Normal Flexion=4; Abnormal Flexion=3; Extension=2; None=1; Not tested	Baseline, 4 weeks (T1), 8 weeks (T2), and 3-,6-,12-months post intervention (T3)
Glasgow Outcomes Scale- Extended (GOSE)	The GOSE is a scale for functional outcome following a severe traumatic injury. The GOSE is an ordinal variable with the following categories: Dead, Vegetative State, Lower Severe Disability, Upper Severe Disability, Lower Moderate Disability, Upper Moderate Disability, Lower Good Recovery, and Upper Good Recovery. The GOSE score is determined by a structured interview with questions surrounding consciousness, independence inside and outside the home, social and leisure activities and return to normal life among others. The scale is 1-8, level 1 minimum score, level 8 maximum score. A higher score is considered to be a better result. A lower score indicates a worse result.	Baseline, 4 weeks (T1), 8 weeks (T2), and 3-,6-,12-months post intervention (T3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Readmission Rates	Readmission Rates	Baseline, 4 weeks (T1), 8 weeks (T2), and 3-,6-,12-months post intervention (T3)
Nociceptive Coma Scale- Revised (NCS-R)	The NCS-R evaluates behavioral responses to painful stimuli through three subscales: motor, verbal, and facial responses. Each subscale is scored from 0 (no response) to 3 (highest response level), with a total score ranging from 0 to 9, where higher scores indicate greater pain awareness.	Baseline, 4 weeks (T1), 8 weeks (T2), and 3-,6-,12-months post intervention (T3)
Number of Physicians Follow-Up Visits	Number of Physicians Follow-Up Visits	Baseline, 4 weeks (T1), 8 weeks (T2), and 3-,6-,12-months post intervention (T3)
Number of Emergency Room Visits	Number of Emergency Room Visits	Baseline, 4 weeks (T1), 8 weeks (T2), and 3-,6-,12-months post intervention (T3)

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Investigators: Principal Investigator: Jenna Tosto-Mancuso, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2025
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: April 9, 2025
• First Submitted That Met QC Criteria: April 9, 2025
• First Posted (Actual): April 16, 2025

Study Record Updates

• Last Update Posted (Estimated): September 19, 2025
• Last Update Submitted That Met QC Criteria: September 15, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Rehabilitation; Neuromodulation; Therapy
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Wounds and Injuries; Neurobehavioral Manifestations; Neurocognitive Disorders; Craniocerebral Trauma; Trauma, Nervous System; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Brain Injuries; Consciousness Disorders; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care
• Other Study ID Numbers: STUDY-24-01339

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All of the individual participant data collected during the trial, after deidentification.
• IPD Sharing Time Frame: Immediately following publication. No end date.

IPD Sharing Access Criteria

Researchers who provide a methodologically sound proposal. Any purpose.

Proposals should be directed to AbilitiesResearchCenter@mountsinai.org. To gain access, data requestors will need to sign a data access agreement. Data are available for 5 years at a third party website (to be determined).

• IPD Sharing Supporting Information Type: ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No