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

Trial Summary

What is the purpose of this trial?

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.

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 data supports the effectiveness of the treatment Vagus Nerve Stimulation for Chronic Consciousness Disorders?

Research shows that vagus nerve stimulation (VNS) can improve brain activity and recovery in patients with consciousness disorders, and has been effective in enhancing recovery after brain injuries and improving mood and cognition in other conditions like epilepsy and depression. ^{1 2 3 4 5}

Is vagus nerve stimulation safe for humans?

Vagus nerve stimulation (VNS) has been shown to be safe and well tolerated in various studies, including those for treating migraines and depression, as well as improving motor function after a stroke. ^{1 3 6 7 8}

How does the treatment Vagus Nerve Stimulation for Chronic Consciousness Disorders differ from other treatments?

Vagus Nerve Stimulation (VNS) is unique because it involves stimulating a nerve in the body to help improve brain function, which can enhance recovery in patients with consciousness disorders. This approach is different from traditional treatments as it pairs nerve stimulation with physical therapy to promote brain plasticity (the brain's ability to change and adapt), potentially leading to better outcomes. ^{1 2 3 9 10}

Research Team

Jenna Tosto-Mancuso

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Stimulation of vagus nerve for patients with disorders of consciousness: a systematic review. [2023]

2. China pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vague nerve stimulation improved brain connection activity on patients of disorders of consciousness: a pilot study. [2023]

3. United States 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. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation to augment recovery from severe traumatic brain injury impeding consciousness: a prospective pilot clinical trial. [2022]

5. Spain pubmed.ncbi.nlm.nih.gov

Transcutaneous vagal nerve stimulation to treat disorders of consciousness: Protocol for a double-blind randomized controlled trial. [2022]

6. England 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. [2020]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of vagus nerve stimulation on upper extremity motor function in patients with stroke: A meta-analysis of randomized controlled trials. [2023]

8. United States 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. [2012]

9. United States pubmed.ncbi.nlm.nih.gov

Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Enhancing plasticity in central networks improves motor and sensory recovery after nerve damage. [2022]