Vagus Nerve Stimulation for Chronic Consciousness Disorders

Overseen By Jenna Tosto-Mancuso, PT, DPT, NCS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Icahn School of Medicine at Mount Sinai

Disqualifiers: Emergence from MCS, Cardiovascular conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 21

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment method for individuals with prolonged disorders of consciousness (lasting over three months) following a severe brain injury. It combines vagus nerve stimulation—a small device that sends electrical pulses to a nerve in the ear—with robotic tilt table mobilization, a machine that aids body movement, to assess improvements in recovery. The trial aims to determine if this combined approach is safe and effective for enhancing functional recovery. Participants should have a consciousness disorder lasting more than three months and be able to safely engage in physical therapy using Hocoma. As an unphased trial, this study provides a unique opportunity to contribute to pioneering research that could improve recovery methods for future patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What prior data suggests that this protocol is safe for patients with prolonged disorders of consciousness?

A previous study found that transcutaneous auricular vagus nerve stimulation (taVNS) was both effective and safe for patients with consciousness disorders. Out of six studies, five showed positive results, suggesting that taVNS is generally well-tolerated. While research continues, this information offers reassurance about the safety of taVNS for those considering joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the combination of transauricular vagus nerve stimulation (taVNS) and robotic tilt table mobilization (RTTM) because it offers a novel approach to treating chronic consciousness disorders. Unlike traditional treatments such as sensory stimulation programs or pharmacological interventions, this method directly stimulates the vagus nerve through the ear, potentially enhancing communication between the brain and the body. Additionally, pairing this nerve stimulation with RTTM—a technique that uses robotic technology to aid in physical therapy—could maximize functional recovery by promoting more effective motor learning and neural plasticity. This innovative combination could provide a new pathway for recovery in patients with prolonged disorders of consciousness (pDOC).

What evidence suggests that this trial's treatments could be effective for chronic consciousness disorders?

Studies have shown that transcutaneous auricular vagus nerve stimulation (taVNS), tested in this trial, might help patients with brain injuries regain consciousness. Research suggests that taVNS boosts brain function by stimulating the vagus nerve, which influences many body functions, including wakefulness and alertness. Some studies have indicated that taVNS could effectively aid patients with long-term consciousness disorders. While researchers continue to collect data, early results suggest it could be a promising treatment for improving recovery in these patients. ^{1 3 4 6 7}

Who Is on the Research Team?

Jenna Tosto-Mancuso

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

This trial is for patients with prolonged disorders of consciousness (pDOC) due to severe brain injuries, who have been in this state for over a year if injury is traumatic, or over three months if non-traumatic. Specific eligibility criteria are not provided.

Inclusion Criteria

I have been in a state of minimal consciousness for over 3 months.

Doctors say I'm fit for physical therapy.

Exclusion Criteria

Patients who have emerged from MCS (CRS-R score 6 on Motor Function scale and/or 2 on Communication Scale)

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)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Observation

Participants are assessed using CRS-R, GCS, and GOSE and continue with 4 weeks of their current standard of care

4 weeks

2 visits (in-person)

Mobilization Only

Participants complete 8 sessions of physical therapy over 4 weeks using a robotic tilt table

4 weeks

8 visits (in-person)

Paired taVNS + RTTM Intervention

Participants receive paired transauricular vagus nerve stimulation and robotic tilt table mobilization

4 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with assessments at 3-, 6-, and 12-months post intervention

12 months

3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Physical therapy using Hocoma
• Transcutaneous vagus nerve stimulation (taVNS)

Trial Overview The study tests pairing transcutaneous auricular vagus nerve stimulation (taVNS) with robotic tilt table mobilization (RTTM). Fifteen participants will undergo a 12-week rehabilitation protocol to see how safe and effective this combination is for functional recovery.

How Is the Trial Designed?

Group I: Patients with Prolonged Disorders of Consciousness (pDOC) Experimental Treatment 3 Interventions

Patients with pDOC receiving paired transauricular vagus nerve stimulation (taVNS) and robotic tilt table mobilization (RTTM) to maximize functional recovery,

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Published Research Related to This Trial

In a study involving stroke survivors with chronic arm weakness, Vagus Nerve Stimulation (VNS) combined with rehabilitation led to a significant improvement in upper extremity function, with an average increase of 5.0 points in the Fugl-Meyer Assessment score compared to 2.4 points in the control group.

The effectiveness of VNS treatment was consistent across various subgroups, including age, severity of impairment, and time since stroke, indicating that VNS could be a broadly applicable intervention for improving arm function in diverse stroke patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus Nerve Stimulation Paired With Rehabilitation for Upper Limb Motor Impairment and Function After Chronic Ischemic Stroke: Subgroup Analysis of the Randomized, Blinded, Pivotal, VNS-REHAB Device Trial. Dawson, J., Engineer, ND., Cramer, SC., et al.[2023]

In the PRESTO trial involving 248 patients with episodic migraine, non-invasive vagus nerve stimulation (nVNS) significantly increased the likelihood of achieving pain relief at 60 and 120 minutes post-treatment compared to a sham device, demonstrating its efficacy as an acute treatment.

The safety profile of nVNS was strong, with low incidence of adverse events and no serious adverse events reported, suggesting it is a reliable option for migraine treatment that can be used alongside traditional medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consistent effects of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine: additional findings from the randomized, sham-controlled, double-blind PRESTO trial. Martelletti, P., Barbanti, P., Grazzi, L., et al.[2020]

Transcutaneous auricular vagus nerve stimulation (taVNS) shows potential as a treatment for disorders of consciousness, particularly in patients with a minimally conscious state (MCS), as it significantly alters brain activity measured by EEG.

In patients with MCS, taVNS led to notable changes in both delta and beta brain wave energy across multiple regions, suggesting it may enhance brain connectivity and promote awakening.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vague nerve stimulation improved brain connection activity on patients of disorders of consciousness: a pilot study. Yifei, W., Yi, Y., Yu, W., et al.[2023]

Vagus nerve stimulation (VNS) can enhance neural plasticity when paired with rehabilitative therapies, potentially improving recovery from various neurological disorders such as stroke and traumatic brain injury.

Initial pilot clinical trials suggest that VNS-based therapies may be effective for patients with neurological diseases, indicating a promising avenue for enhancing rehabilitation outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation. Hays, SA.[2022]

In a study of 15 patients with treatment-resistant depression, vagus nerve stimulation (VNS) significantly reduced depression scores over 12 months, with a mean Beck Depression Inventory score dropping from 37.8 to 24.6, indicating a positive treatment effect.

By the end of the year, 28.6% of patients showed a response to VNS, and 7.1% achieved remission, with side effects like hoarseness and nausea being common but not leading to treatment discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of vagus nerve stimulation for severe treatment-resistant major depression in clinical practice after FDA approval: outcomes at 1 year. Cristancho, P., Cristancho, MA., Baltuch, GH., et al.[2012]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11149147/

Transcutaneous auricular vagal nerve stimulation for ... We developed a protocol for a randomised controlled study to evaluate the effectiveness of taVNS on consciousness recovery in patients with pDoC (TAVREC).

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06930716

Paired Vagus Nerve Stimulation in Mobilization of Patients ... This study will report on the safety, feasibility, and preliminary short- and long-term outcomes of RTTM with simultaneously paired Transcutaneous auricular ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1697260022000680

Transcutaneous vagal nerve stimulation to treat disorders ... We will conduct a prospective parallel randomized controlled double-blind clinical trial investigating the effects of taVNS as a treatment in DoC patients.

4. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2023.1116115/full

Randomized trial of transcutaneous auricular vagus nerve ... Background: The potential effectiveness of taVNS in the course of consciousness recovery has been highlighted by recent studies with brain injury patients.

5. mountsinai.org mountsinai.org/clinical-trials/paired-vagus-nerve-stimulation-in-mobilization-of-patients-with-prolonged-disorders-of-consciousness

Paired Vagus Nerve Stimulation in Mobilization of Patients ... This study will report on the safety, feasibility, and preliminary short- and long-term outcomes of RTTM with simultaneously paired Transcutaneous auricular ...

6. journals.lww.com journals.lww.com/md-journal/fulltext/2022/12160/transcutaneous_auricular_vagus_nerve_stimulation.84.aspx

Transcutaneous auricular vagus nerve stimulation in... Generally, the application of taVNS in patients with DOC appears to be effective (positive results in 5 of 6 studies) and safe.

7. frontiersin.org frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2023.1257378/full

Stimulation of vagus nerve for patients with disorders ... The purpose of this study is to evaluate the efficacy and safety of stimulating the vagus nerve in patients with disorders of consciousness (DOCs).