Electrical Impedance Tomography & Selective Stimulation of Vagus Nerve

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-12-04

Study Completion Date

2027-01-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Electroceuticals is a new field in which the goal is to treat a wide variety of medical diseases with electrical stimulation of autonomic nerves. A prime target for intervention is the cervical vagus nerve as it is easily surgically accessible and supplies many organs in the neck, thorax and abdomen. It would be desirable to stimulate selectively in order to avoid the off-target effects that currently occur. This has not been tried in the past, both because of limitations in available technology but also because, surprisingly, the fascicular organisation of the cervical vagus nerve is almost completely unknown. The aim of this research is to investigate the functional anatomy of fascicles in the cervical vagus nerve of humans. This will include defining innervation to the heart, lungs and recurrent laryngeal and, if possible, the oesophagus, stomach, pancreas, liver and gastrointestinal tract. It will be achieved by defining fascicle somatotopic functional anatomy with spatially-selective vagus nerve stimulation (sVNS) and the new method of fast neural imaging with Electrical Impedance Tomography (EIT). EIT is a novel imaging method in which reconstructed tomographic images of resistance changes related to the opening of ion channels over milliseconds can be produced using rings or arrays of external electrodes. In humans, using a nonpenetrating nerve cuff with sVNS or fast neural EIT, this will be performed for 30 minutes transiently during an operation to insert a vagal nerve stimulator for treatment of epilepsy and deliver images in response to activity such as respiration or the electrocardiogram (ECG).

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Transcutaneous Non-invasive Stimulation of the Vagus Nerve for the Treatment of Difficult-to-treat Epilepsy

NCT01178437

Epilepsy

COMPLETED NA

Optimization of VNS in Epileptic Patients to Induce Cardioprotection

NCT04387435

Epilepsy Sudden Cardiac Death

COMPLETED NA

Does Pulse-triggered VNS Autostimulation Increase VNS Efficacy

NCT04095247

Epilepsy

TERMINATED

Microelectrode Recordings From the Vagus Nerve in Awake Humans

NCT06016686

Epilepsy

RECRUITING PHASE1

Trial Comparing Different Stimulation Paradigms in Patients Treated With Vagus Nerve Stimulation for Refractory Epilepsy

NCT00782249

Epilepsy

COMPLETED NA

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Electroceuticals is a relatively new field in which the goal is to treat a wide variety of medical diseases with electrical stimulation of autonomic nerves. A prime target for intervention is the cervical vagus nerve as it is easily surgically accessible and supplies many organs in the neck, thorax and abdomen. It would be desirable to stimulate selectively in order to avoid the off-target effects that currently occur. Until recently, this has not been tried in the past, both because of limitations in available technology but also because, surprisingly, the fascicular organisation of the cervical vagus nerve is almost completely unknown; work has recently been performed in animal models. The aim of this research is to investigate the functional anatomy of fascicles (groups of nerve fibres) in the cervical vagus nerve of humans. This will include defining innervation to the heart, lungs and recurrent laryngeal and, if possible, the oesophagus, stomach, pancreas, liver and gastrointestinal tract. After the specific locations of above groups are identified, it will be possible to direct the stimulation so that only specific organs are affected by the vagus nerve stimulation. In particular, it may be possible to achieve a therapeutic seizure-suppressive effect in Epilepsy with better efficacy, and, at the same time, avoid all side effects normally present because all of the organ functions are altered when the entire nerve gets stimulated.

Our group has pioneered the use of a multi-purpose nerve cuff for imaging activity within nerves with Electrical Impedance Tomography (EIT) and with the ability of spatially-selective neuromodulation. It has been optimised and validated for use in vivo in animal models.

Vagus nerve stimulation (VNS) is currently perform in humans for the treatment of drug-resistant epilepsy and depression. However, VNS as a therapeutic intervention can be expanded to a vast range of therapeutic applications. Ongoing studies and preclinical research indicate promising results in treating cardiovascular disorders and heart failure, lung injury, asthma, sepsis, rheumatoid arthritis, diabetes, obesity, pain management and targeting the anti-inflammatory pathway in general. In addition, selective neuromodulation could be used as a therapeutic approach for the treatment of acute respiratory distress syndrome, predominant currently during the Covid-19 pandemic, which requires the activation of some pathways (cholinergic anti-inflammatory pathway) and not others (pulmonary function) to effectively improve outcomes.

Even with the vast potential of VNS in treating a variety of diseases, limitations still exist. Without the knowledge of the neuroanatomy of the target nerve, side effects prevail and reduce the efficacy of treatment. A large proportion of side-effects frequently experienced, including cough, dyspnoea and hoarseness, can be attributed to activation of the recurrent laryngeal nerve fibres in the vagus nerve. Avoidance of vagal outflow to the larynx alone could greatly improve VNS and reduce the side effects so often observed. However, knowledge of the innervation from all regions within the cervical vagus nerve could further improve targeted stimulation and therapeutic efficacy; avoiding any unwanted responses in non-targeted organs such as shortness of breath and bradycardia and could reduce the risk of further, long-term side effects, such as developing hyperglycaemia when stimulating for epilepsy.

EIT and selective stimulation of the human vagus nerve holds promise to provide information of the fascicular organisation of the nerve which would allow for targeted neuromodulation during the treatment of epilepsy, depression and other disorders without indiscriminate vagal outflow thereby avoiding off-target effects currently experienced. The efficacy and therapeutic outcomes of VNS will be improved. It requires interdisciplinary collaboration from biomedical scientists, electronic engineers and mathematicians, and holds great interest for those interested in interdisciplinary work in these fields.

During routine vagal nerve stimulator implantation surgery, the operating surgeon will place a temporary electrode cuff for the purpose of this study only, after gaining access to the vagus nerve. This cuff will be removed during the same surgery after the protocol has been completed, and the surgery completed as usual. This cuff is designed for single use, made of sterilised platinum and medical-grade silicone - a layer of platinum containing traces and electrodes arranged in rings is confined between two layers of medical-grade silicone. To ensure the cuff is in contact with the nerve, a medical-grade silicone support, in the form of a tube with an opening, or biocompatible clamps attached to the opening ends of the cuff will be used at the discretion of the surgeon. One end of the cuff has a connector leading to an electronic device that is used for the stimulations and recordings. Whilst the patient is still under for their routine implantation surgery, both selective stimulation and EIT recordings (imaging) will take place. An electrical current will be driven between a pair of electrodes present on the cuff, and the process will be repeated for different pairs while recording physiological parameters (ECG (recording of the heart activity), respiration, electrogastrogram) to look for physiological changes. Parameters, such as current, pulse width and frequency, will be adjusted to elicit responses in the nerve by different nerve fibre types. Stimulation will be performed for approximately up to 28 minutes (10 to 30 seconds per pair with waiting time in between to return to baseline). This may be repeated with different stimulation parameters. Subsequently, nerve imaging (EIT) will be performed in a similar way with current injected through various electrode pairs; however, this time other electrodes on the cuff will be used to record electrical properties, specifically impedance, from the nerve. This will take place for approximately 28 minutes as well. The cuff will be removed by the surgeon at the end of the protocol and the surgery will be completed as usual for the standard implantation surgery. This will complete the involvement of the patient in this study. All measurements and recordings will be analysed at a later stage by the researchers in their lab and office, to get information about selective vagus nerve stimulation and form images of the activity within the nerve and the level of cuff implantation.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Vagus Nerve Diseases Epilepsy Vagus Nerve Autonomic Disorder

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

sVNS and EIT of cervical vagus nerve

Selective vagus nerve stimulation (sVNS) with a spatially selective vagal nerve cuff with physiological readouts such as electrocardiogram (ECG), heart rate, end-tidal carbon dioxide (EtCO2), respiratory rate, laryngeal electromyogram (EMG), etc., and electrical impedance tomography (EIT) recordings of the nerve.

Group Type EXPERIMENTAL

Nerve cuff electrodes for spatially selective vagus nerve stimulation and electrical impedance tomography

Intervention Type DEVICE

Vagus nerve electrode cuffs will be placed on the exposed human vagus nerve during routine vagal nerve stimulator implantation surgery. These cuffs will then be used for spatially selective vagus nerve stimulation, with physiological readout, and electrical impedance tomography for the functional imaging of organ-specific regions in the nerve at cervical level.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Nerve cuff electrodes for spatially selective vagus nerve stimulation and electrical impedance tomography

Vagus nerve electrode cuffs will be placed on the exposed human vagus nerve during routine vagal nerve stimulator implantation surgery. These cuffs will then be used for spatially selective vagus nerve stimulation, with physiological readout, and electrical impedance tomography for the functional imaging of organ-specific regions in the nerve at cervical level.

Intervention Type DEVICE

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Age over 18
* Written informed consent by patient or proxy
* Clinical diagnosis of disorder affected directly or indirectly or will possibly respond to vagus nerve stimulation

Exclusion Criteria

* Aged 17 and below
* Unfortunately, it is unlikely that interpreters of all languages will be available in the unit so persons who cannot understand verbal explanation in English and for whom we could not find a suitable consultee would have to be excluded from the study.

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No