Vagus Nerve StimulationVNS-KTxNCT04256837
Effect of Transcutaneous Electrical Auricular Stimulation of the Vagus Nerve in Kidney Transplant Recipients
A study testing Transcutaneous electrical auricular vagus nerve stimulation (VNS) in people with Vagus Nerve Stimulation, run by Northwell Health at 1 site in United States.
Trial summary
Kidney transplantation entails the implantation of a live or deceased organ into a recipient. As a result of this event, there is an inflammatory response in the recipient elicited by the transplanted organ. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Vagus Nerve Stimulation
- What is being tested?
- Transcutaneous electrical auricular vagus nerve stimulation (VNS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 47 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Jan 2020to 7 Jan 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Kidney transplant recipients of both live and deceased donors
Who cannot join
- Refusal to participate in the study
Trial locations and contacts
1 site in 1 country.
About this study
Kidney transplantation entails the implantation of a live or deceased organ into a recipient. As a result of this event, there is an inflammatory response in the recipient elicited by the transplanted organ.
At the present time, immunosuppressive treatments are routinely used to avoid rejection of the transplanted organ. Although effective in this goal, there is currently an unmet need to develop new strategies to control the innate inflammatory responses and to reduce the injury caused to the organs being transplanted.
Read more
The investigators propose a novel approach to the management of this inflammatory response. The investigators will explore the "cholinergic anti-inflammatory pathway" as a potential target, a pathway first characterized in the basic science laboratories of the Feinstein Institute for Medical Research. In short, the vagus nerve activates the splenic nerve which activates choline acetyltransferase expressing T cells in the spleen. Stimulation of the alpha7 nicotinic acetylcholine receptor (alpha7nAChR) on macrophages by acetylcholine reduces production of multiple pro-inflammatory cytokines.
Currently, vagus nerve stimulation is used to treat a number of human diseases, including epilepsy, depression and migraine headaches. Many of these treatments activate the vagus nerve non-invasively by stimulating a branch of the vagus that innervates the ear. In this study, the investigators will stimulate this branch of the vagus nerve, and look for changes in inflammatory markers in the blood of kidney transplant recipients of both live and deceased donors.
Successful completion of this study will allow for future studies in organ transplant recipients.
Read the detailed description
Intervention and comparators:
Patients will receive transcutaneous stimulation of the auricular branch of the left vagus nerve for 5 minutes in the OR already under anesthesia. Subjects will be blinded to their treatment arm.
The device to be used will include a handheld electrical pulse generator and a pair of electrodes to be placed at the ear for stimulation. The specific target at the ear will be the auricular branch of the vagus nerve which innervates the skin overlying the cymba conchae of the ear canal.
Anatomical landmarks and cutaneous innervation of the external ear. Three nerves contribute to the cutaneous innervation of the lateral aspect of the ear: the auricular branch of the vagus nerve (ABVN), the auriculotemporal nerve (ATN) and the great auricular nerve (GAN). There is a variable degree of overlap in the distribution of these cutaneous nerves.
Electrodes will be placed near/at the entrance to the canal of the ear to provide stimulation to the auricular branch. The handheld electrical pulse generator (e.g. Roscoe Medical, TENS 7000) will be programmed to deliver stimulation pulses to the electrodes. The electrodes will be made of conductive material facilitating trans-cutaneous electrical stimulation. All subjects will be told that they may or may not sense the stimulation.
Attempts to diminish pain associated with blood drawing will be made by performing whenever possible the phlebotomy coincident with other blood drawing requirements or while the patient is under anesthesia.
The investigators will administer transcutaneous electrical stimulation to the left ears for 5 minutes. Subjects receiving auricular stimulation will receive stimulation using the following parameters: 0.300 milliseconds (msec) stimulus peaks at a frequency of 30 Hz for five (5) minutes, with peak current pulse amplitude set to 1.5 milliamps (mA). Research subjects will receive hemodynamic monitoring and heart rate variability monitoring while undergoing vagal stimulation as a routine part of the underlying care for organ procurement or anesthesia management.
Transcutaneous electrical stimulation Electrical auricular stimulation is accomplished using a Roscoe Medical TENS 7000 that delivers a programmable electrical current density, frequency, and pulse width. The TENS 7000 will be connected to ear clip (or hand held) electrodes to transcutaneously stimulate the cymba conchae of the ear to activate the auricular branch of the vagus nerve (diagram above), also known as Arnold's nerve, which provides sensory innervation to the skin surrounding the ear canal. Through a neural reflex arc, activation of this sensory nerve sends a neural signal to the brainstem that then activates the efferent vagus nerve through the nucleus of the solitary tract (NTS). This is a well-described and clinically accepted neuromodulatory pathway, as transcutaneous electrical auricular stimulation has been studied to treat seizures, similarly to how invasive electrical vagus nerve stimulation has been approved by the FDA for the past two decades for the same indication. Currently, transcutaneous electrical auricular stimulation is approved in Europe for the treatment of seizures.
The scientific basis for these specific choices comes from more than 10 years of experience performing experimental vagus nerve stimulation in animals to control bleeding at The Feinstein Institute for Medical Research. The frequency of stimulus peaks will be 30 Hz. The pulse width of the individual stimulus peaks will be 0.300 milliseconds (msec). The total duration of stimulation will be five (5) minutes. For the remaining stimulation parameter, which is the peak current pulse amplitude, the investigators will use 1.5 milliamps (mA). These stimulation parameters are very similar to parameters previously demonstrated to be safe in two separate tinnitus studies (6, 7). A portable, battery-powered oscilloscope will be used to confirm peak current.
Safety procedures Recent assessments of cardiac safety following transcutaneous electrical stimulation of the auricular branch of the vagus nerve have revealed no indication of arrhythmic effects of tVNS (6, 7).
In the exceedingly rare instance that a research subject develops a symptomatic bradyarrhythmia, qualified personnel anesthesiologists/surgeons/residents/CRNA) will be immediately available to administer any therapies (intravenous fluid, anti-arrhythmic medications, cardioversion) to treat the bradyarrhythmia and its associated symptoms.
- Conditions
- Vagus Nerve Stimulation
- Being tested
- Transcutaneous electrical auricular vagus nerve stimulation (VNS)
- Keywords
- Vagus Nerve, Stimulation, Immune System
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcutaneous electrical auricular vagus nerve stimulation (VNS)Device
Electrical auricular stimulation is accomplished using a Roscoe Medical TENS 7000 that delivers a programmable electrical current density, frequency, and pulse width. The TENS 7000 will be connected to ear clip (or hand held) electrodes to transcutaneously stimulate the cymba conchae of the ear to activate the auricular branch of the vagus nerve (diagram above), also known as Arnold's nerve, which provides sensory innervation to the skin surrounding the ear canal. Through a neural reflex arc, activation of this sensory nerve sends a neural signal to the brainstem that then activates the efferent vagus nerve through the nucleus of the solitary tract (NTS). This is a well-described and clinically accepted neuromodulatory pathway, as transcutaneous electrical auricular stimulation has been studied to treat seizures, similarly to how invasive electrical vagus nerve stimulation has been approved by the FDA for the past two decades for the same indication.
| Study group | Role | What they receive |
|---|---|---|
| VNS - Live donor kidney recipients. | Experimental | Live donor kidney recipients. VNS will be applied for 5 minutes prior to start of surgery. The device to be used for VNS will include a handheld electrical pulse generator and a pair of electrodes to be placed at the left ear for stimulation, targeting the auricular branch of the vagus nerve which innervates the skin overlying the cymba conchae of the ear canal. Receives: Device: Transcutaneous electrical auricular vagus nerve stimulation (VNS) |
| sham VNS - Live donor kidney recipients. | Sham comparator | Live donor kidney recipients. As above, but without applying any VNS Receives: Device: Transcutaneous electrical auricular vagus nerve stimulation (VNS) |
| VNS - Deceased donor kidney recipients. | Experimental | Deceased donor kidney recipients. VNS will be applied for 5 minutes prior to start of surgery. The device to be used for VNS will include a handheld electrical pulse generator and a pair of electrodes to be placed at the left ear for stimulation, targeting the auricular branch of the vagus nerve which innervates the skin overlying the cymba conchae of the ear canal. Receives: Device: Transcutaneous electrical auricular vagus nerve stimulation (VNS) |
| sham VNS - Deceased donor kidney recipients. | Sham comparator | Deceased donor kidney recipients. As above, but without applying any VNS Receives: Device: Transcutaneous electrical auricular vagus nerve stimulation (VNS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Levels of blood inflammatory cytokines in kidney transplant recipients after transcutaneous auricular electrical vagus nerve stimulation.
The present study will measure systemic cytokines IL-1, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-17, IL-22, IL-23, TNF, IFN-gamma, HMGB1, TGF-beta, GM-CSF, CXCL8, G-CSFas well as complement 1-9 in the blood of kidney transplant recipients who have undergone transcutaneous auricular electrical vagus nerve stimulation.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2020
- Study start13 Jan 2020
- Primary completion7 Jan 2021
- Study completion7 Jan 2021
Why it stopped: The study expired and was not renewed with the IRB
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (18)Papers the sponsor has linked to this study.
- Other trials for Vagus Nerve StimulationStudies of the same condition, open and under way.
- More trials run by Northwell HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Model description
- The objective of this pilot, feasibility study is to examine the effects of transcutaneous electrical auricular vagus nerve stimulation (VNS) in adult patients undergoing a single kidney transplant using donors who are either living or deceased. Kidney transplantation patients will be stratified into two groups, namely, those receiving their kidney from a living donor and those receiving their kidney from a deceased donor. Within each strata, patients will be randomized to receive either active VNS or sham VNS. VNS will be applied for 5 minutes prior to start of surgery. The device to be used for VNS will include a handheld electrical pulse generator and a pair of electrodes to be placed at the left ear for stimulation, targeting the auricular branch of the vagus nerve which innervates the skin overlying the cymba conchae of the ear canal.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwell Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ernesto P Molmenti, MD PhD MBA, Principal investigator, Northwell Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04256837
- Sponsor's protocol ID
- 19-0705
- Acronym
- VNS-KTx
- Status last verified
- Dec 2022
- First submitted
- 21 Jan 2020
- Last updated
- 14 Dec 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Information on live and deceased donors will be limited to that provided by the UNOS ID that does not contain any PHI.
Publications
Panebianco M, Rigby A, Weston J, Marson AG. Vagus nerve stimulation for partial seizures. Cochrane Database Syst Rev. 2015 Apr 3;2015(4):CD002896. doi: 10.1002/14651858.CD002896.pub2.
PubMed 25835947Yuan H, Silberstein SD. Vagus Nerve and Vagus Nerve Stimulation, a Comprehensive Review: Part II. Headache. 2016 Feb;56(2):259-66. doi: 10.1111/head.12650. Epub 2015 Sep 18.
PubMed 26381725Ben-Menachem E. Vagus nerve stimulation, side effects, and long-term safety. J Clin Neurophysiol. 2001 Sep;18(5):415-8. doi: 10.1097/00004691-200109000-00005.
PubMed 11709646Yuan H, Silberstein SD. Vagus Nerve and Vagus Nerve Stimulation, a Comprehensive Review: Part III. Headache. 2016 Mar;56(3):479-90. doi: 10.1111/head.12649. Epub 2015 Sep 14.
PubMed 26364805Ben-Menachem E, Revesz D, Simon BJ, Silberstein S. Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. Eur J Neurol. 2015 Sep;22(9):1260-8. doi: 10.1111/ene.12629. Epub 2015 Jan 23.
PubMed 25614179Kreuzer PM, Landgrebe M, Husser O, Resch M, Schecklmann M, Geisreiter F, Poeppl TB, Prasser SJ, Hajak G, Langguth B. Transcutaneous vagus nerve stimulation: retrospective assessment of cardiac safety in a pilot study. Front Psychiatry. 2012 Aug 7;3:70. doi: 10.3389/fpsyt.2012.00070. eCollection 2012.
PubMed 22891061Shim HJ, Kwak MY, An YH, Kim DH, Kim YJ, Kim HJ. Feasibility and Safety of Transcutaneous Vagus Nerve Stimulation Paired with Notched Music Therapy for the Treatment of Chronic Tinnitus. J Audiol Otol. 2015 Dec;19(3):159-67. doi: 10.7874/jao.2015.19.3.159. Epub 2015 Dec 18.
PubMed 26771015Huston JM, Tracey KJ. The pulse of inflammation: heart rate variability, the cholinergic anti-inflammatory pathway and implications for therapy. J Intern Med. 2011 Jan;269(1):45-53. doi: 10.1111/j.1365-2796.2010.02321.x.
PubMed 21158977Huston JM, Rosas-Ballina M, Xue X, Dowling O, Ochani K, Ochani M, Yeboah MM, Chatterjee PK, Tracey KJ, Metz CN. Cholinergic neural signals to the spleen down-regulate leukocyte trafficking via CD11b. J Immunol. 2009 Jul 1;183(1):552-9. doi: 10.4049/jimmunol.0802684.
PubMed 19542466Huston JM, Wang H, Ochani M, Ochani K, Rosas-Ballina M, Gallowitsch-Puerta M, Ashok M, Yang L, Tracey KJ, Yang H. Splenectomy protects against sepsis lethality and reduces serum HMGB1 levels. J Immunol. 2008 Sep 1;181(5):3535-9. doi: 10.4049/jimmunol.181.5.3535.
PubMed 18714026Rosas-Ballina M, Ochani M, Parrish WR, Ochani K, Harris YT, Huston JM, Chavan S, Tracey KJ. Splenic nerve is required for cholinergic antiinflammatory pathway control of TNF in endotoxemia. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):11008-13. doi: 10.1073/pnas.0803237105. Epub 2008 Jul 31.
PubMed 18669662Huston JM, Gallowitsch-Puerta M, Ochani M, Ochani K, Yuan R, Rosas-Ballina M, Ashok M, Goldstein RS, Chavan S, Pavlov VA, Metz CN, Yang H, Czura CJ, Wang H, Tracey KJ. Transcutaneous vagus nerve stimulation reduces serum high mobility group box 1 levels and improves survival in murine sepsis. Crit Care Med. 2007 Dec;35(12):2762-8. doi: 10.1097/01.CCM.0000288102.15975.BA.
PubMed 17901837Huston JM, Ochani M, Rosas-Ballina M, Liao H, Ochani K, Pavlov VA, Gallowitsch-Puerta M, Ashok M, Czura CJ, Foxwell B, Tracey KJ, Ulloa L. Splenectomy inactivates the cholinergic antiinflammatory pathway during lethal endotoxemia and polymicrobial sepsis. J Exp Med. 2006 Jul 10;203(7):1623-8. doi: 10.1084/jem.20052362. Epub 2006 Jun 19.
PubMed 16785311Rosas-Ballina M, Olofsson PS, Ochani M, Valdes-Ferrer SI, Levine YA, Reardon C, Tusche MW, Pavlov VA, Andersson U, Chavan S, Mak TW, Tracey KJ. Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit. Science. 2011 Oct 7;334(6052):98-101. doi: 10.1126/science.1209985. Epub 2011 Sep 15.
PubMed 21921156Wang H, Liao H, Ochani M, Justiniani M, Lin X, Yang L, Al-Abed Y, Wang H, Metz C, Miller EJ, Tracey KJ, Ulloa L. Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nat Med. 2004 Nov;10(11):1216-21. doi: 10.1038/nm1124. Epub 2004 Oct 24.
PubMed 15502843
Study at a glance
From the registry record, last updated by the sponsor on 14 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Transcutaneous Electrical Auricular Stimulation of the Vagus Nerve in Kidney Transplant Recipients
- ClinicalTrials.gov ID
- NCT04256837
- Acronym / sponsor ID
- VNS-KTx / 19-0705
- Conditions
- Vagus Nerve Stimulation
- Keywords
- Vagus Nerve, Stimulation, Immune System
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study expired and was not renewed with the IRB
- Enrolment
- 47 participants (actual)
- Lead sponsor
- Northwell HealthUniversity, hospital or other
- Study start
- 13 Jan 2020 (actual)
- Primary completion
- 7 Jan 2021 (actual)
- Study completion
- 7 Jan 2021 (actual)
- First posted
- 5 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Kidney transplantation entails the implantation of a live or deceased organ into a recipient. As a result of this event, there is an inflammatory response in the recipient elicited by the transplanted organ.
At the present time, immunosuppressive treatments are routinely used to avoid rejection of the transplanted organ. Although effective in this goal, there is currently an unmet need to develop new strategies to control the innate inflammatory responses and to reduce the injury caused to the organs being transplanted.
The investigators propose a novel approach to the management of this inflammatory response. The investigators will explore the "cholinergic anti-inflammatory pathway" as a potential target, a pathway first characterized in the basic science laboratories of the Feinstein Institute for Medical Research. In short, the vagus nerve activates the splenic nerve which activates choline acetyltransferase expressing T cells in the spleen. Stimulation of the alpha7 nicotinic acetylcholine receptor (alpha7nAChR) on macrophages by acetylcholine reduces production of multiple pro-inflammatory cytokines.
Currently, vagus nerve stimulation is used to treat a number of human diseases, including epilepsy, depression and migraine headaches. Many of these treatments activate the vagus nerve non-invasively by stimulating a branch of the vagus that innervates the ear. In this study, the investigators will stimulate this branch of the vagus nerve, and look for changes in inflammatory markers in the blood of kidney transplant recipients of both live and deceased donors.
Successful completion of this study will allow for future studies in organ transplant recipients.
Detailed description
Intervention and comparators:
Patients will receive transcutaneous stimulation of the auricular branch of the left vagus nerve for 5 minutes in the OR already under anesthesia. Subjects will be blinded to their treatment arm.
The device to be used will include a handheld electrical pulse generator and a pair of electrodes to be placed at the ear for stimulation. The specific target at the ear will be the auricular branch of the vagus nerve which innervates the skin overlying the cymba conchae of the ear canal.
Anatomical landmarks and cutaneous innervation of the external ear. Three nerves contribute to the cutaneous innervation of the lateral aspect of the ear: the auricular branch of the vagus nerve (ABVN), the auriculotemporal nerve (ATN) and the great auricular nerve (GAN). There is a variable degree of overlap in the distribution of these cutaneous nerves.
Electrodes will be placed near/at the entrance to the canal of the ear to provide stimulation to the auricular branch. The handheld electrical pulse generator (e.g. Roscoe Medical, TENS 7000) will be programmed to deliver stimulation pulses to the electrodes. The electrodes will be made of conductive material facilitating trans-cutaneous electrical stimulation. All subjects will be told that they may or may not sense the stimulation.
Attempts to diminish pain associated with blood drawing will be made by performing whenever possible the phlebotomy coincident with other blood drawing requirements or while the patient is under anesthesia.
The investigators will administer transcutaneous electrical stimulation to the left ears for 5 minutes. Subjects receiving auricular stimulation will receive stimulation using the following parameters: 0.300 milliseconds (msec) stimulus peaks at a frequency of 30 Hz for five (5) minutes, with peak current pulse amplitude set to 1.5 milliamps (mA). Research subjects will receive hemodynamic monitoring and heart rate variability monitoring while undergoing vagal stimulation as a routine part of the underlying care for organ procurement or anesthesia management.
Transcutaneous electrical stimulation Electrical auricular stimulation is accomplished using a Roscoe Medical TENS 7000 that delivers a programmable electrical current density, frequency, and pulse width. The TENS 7000 will be connected to ear clip (or hand held) electrodes to transcutaneously stimulate the cymba conchae of the ear to activate the auricular branch of the vagus nerve (diagram above), also known as Arnold's nerve, which provides sensory innervation to the skin surrounding the ear canal. Through a neural reflex arc, activation of this sensory nerve sends a neural signal to the brainstem that then activates the efferent vagus nerve through the nucleus of the solitary tract (NTS). This is a well-described and clinically accepted neuromodulatory pathway, as transcutaneous electrical auricular stimulation has been studied to treat seizures, similarly to how invasive electrical vagus nerve stimulation has been approved by the FDA for the past two decades for the same indication. Currently, transcutaneous electrical auricular stimulation is approved in Europe for the treatment of seizures.
The scientific basis for these specific choices comes from more than 10 years of experience performing experimental vagus nerve stimulation in animals to control bleeding at The Feinstein Institute for Medical Research. The frequency of stimulus peaks will be 30 Hz. The pulse width of the individual stimulus peaks will be 0.300 milliseconds (msec). The total duration of stimulation will be five (5) minutes. For the remaining stimulation parameter, which is the peak current pulse amplitude, the investigators will use 1.5 milliamps (mA). These stimulation parameters are very similar to parameters previously demonstrated to be safe in two separate tinnitus studies (6, 7). A portable, battery-powered oscilloscope will be used to confirm peak current.
Safety procedures Recent assessments of cardiac safety following transcutaneous electrical stimulation of the auricular branch of the vagus nerve have revealed no indication of arrhythmic effects of tVNS (6, 7).
In the exceedingly rare instance that a research subject develops a symptomatic bradyarrhythmia, qualified personnel anesthesiologists/surgeons/residents/CRNA) will be immediately available to administer any therapies (intravenous fluid, anti-arrhythmic medications, cardioversion) to treat the bradyarrhythmia and its associated symptoms.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind (participant)
- Number of arms
- 4
- Model description
- The objective of this pilot, feasibility study is to examine the effects of transcutaneous electrical auricular vagus nerve stimulation (VNS) in adult patients undergoing a single kidney transplant using donors who are either living or deceased. Kidney transplantation patients will be stratified into two groups, namely, those receiving their kidney from a living donor and those receiving their kidney from a deceased donor. Within each strata, patients will be randomized to receive either active VNS or sham VNS. VNS will be applied for 5 minutes prior to start of surgery. The device to be used for VNS will include a handheld electrical pulse generator and a pair of electrodes to be placed at the left ear for stimulation, targeting the auricular branch of the vagus nerve which innervates the skin overlying the cymba conchae of the ear canal.
| Arm | Type | Receives |
|---|---|---|
| VNS - Live donor kidney recipients. | Experimental | Device: Transcutaneous electrical auricular vagus nerve stimulation (VNS)Live donor kidney recipients. VNS will be applied for 5 minutes prior to start of surgery. The device to be used for VNS will include a handheld electrical pulse generator and a pair of electrodes to be placed at the left ear for stimulation, targeting the auricular branch of the vagus nerve which innervates the skin overlying the cymba conchae of the ear canal. |
| sham VNS - Live donor kidney recipients. | Sham comparator | Device: Transcutaneous electrical auricular vagus nerve stimulation (VNS)Live donor kidney recipients. As above, but without applying any VNS |
| VNS - Deceased donor kidney recipients. | Experimental | Device: Transcutaneous electrical auricular vagus nerve stimulation (VNS)Deceased donor kidney recipients. VNS will be applied for 5 minutes prior to start of surgery. The device to be used for VNS will include a handheld electrical pulse generator and a pair of electrodes to be placed at the left ear for stimulation, targeting the auricular branch of the vagus nerve which innervates the skin overlying the cymba conchae of the ear canal. |
| sham VNS - Deceased donor kidney recipients. | Sham comparator | Device: Transcutaneous electrical auricular vagus nerve stimulation (VNS)Deceased donor kidney recipients. As above, but without applying any VNS |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Kidney transplant recipients of both live and deceased donors
Key exclusion criteria (1 listed)
- Refusal to participate in the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcutaneous electrical auricular vagus nerve stimulation (VNS)Electrical auricular stimulation is accomplished using a Roscoe Medical TENS 7000 that delivers a programmable electrical current density, frequency, and pulse width. The TENS 7000 will be connected to ear clip (or hand held) electrodes to transcutaneously stimulate the cymba conchae of the ear to activate the auricular branch of the vagus nerve (diagram above), also known as Arnold's nerve, which provides sensory innervation to the skin surrounding the ear canal. Through a neural reflex arc, activation of this sensory nerve sends a neural signal to the brainstem that then activates the efferent vagus nerve through the nucleus of the solitary tract (NTS). This is a well-described and clinically accepted neuromodulatory pathway, as transcutaneous electrical auricular stimulation has been studied to treat seizures, similarly to how invasive electrical vagus nerve stimulation has been approved by the FDA for the past two decades for the same indication. | Device | VNS - Deceased donor kidney recipients., VNS - Live donor kidney recipients., sham VNS - Deceased donor kidney recipients., sham VNS - Live donor kidney recipients. |
Primary outcome
Levels of blood inflammatory cytokines in kidney transplant recipients after transcutaneous auricular electrical vagus nerve stimulation.
Time frame: 24 months
The present study will measure systemic cytokines IL-1, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-17, IL-22, IL-23, TNF, IFN-gamma, HMGB1, TGF-beta, GM-CSF, CXCL8, G-CSFas well as complement 1-9 in the blood of kidney transplant recipients who have undergone transcutaneous auricular electrical vagus nerve stimulation.
Results and safety
The study was stopped early (reason given: The study expired and was not renewed with the IRB). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Dec 2022.
- Background: PubMed 25835947Panebianco M, Rigby A, Weston J, Marson AG. Vagus nerve stimulation for partial seizures. Cochrane Database Syst Rev. 2015 Apr 3;2015(4):CD002896. doi: 10.1002/14651858.CD002896.pub2.
- Background: PubMed 26381725Yuan H, Silberstein SD. Vagus Nerve and Vagus Nerve Stimulation, a Comprehensive Review: Part II. Headache. 2016 Feb;56(2):259-66. doi: 10.1111/head.12650. Epub 2015 Sep 18.
- Background: PubMed 11709646Ben-Menachem E. Vagus nerve stimulation, side effects, and long-term safety. J Clin Neurophysiol. 2001 Sep;18(5):415-8. doi: 10.1097/00004691-200109000-00005.
- Background: PubMed 26364805Yuan H, Silberstein SD. Vagus Nerve and Vagus Nerve Stimulation, a Comprehensive Review: Part III. Headache. 2016 Mar;56(3):479-90. doi: 10.1111/head.12649. Epub 2015 Sep 14.
- Background: PubMed 25614179Ben-Menachem E, Revesz D, Simon BJ, Silberstein S. Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. Eur J Neurol. 2015 Sep;22(9):1260-8. doi: 10.1111/ene.12629. Epub 2015 Jan 23.
- Background: PubMed 22891061Kreuzer PM, Landgrebe M, Husser O, Resch M, Schecklmann M, Geisreiter F, Poeppl TB, Prasser SJ, Hajak G, Langguth B. Transcutaneous vagus nerve stimulation: retrospective assessment of cardiac safety in a pilot study. Front Psychiatry. 2012 Aug 7;3:70. doi: 10.3389/fpsyt.2012.00070. eCollection 2012.
- Background: PubMed 26771015Shim HJ, Kwak MY, An YH, Kim DH, Kim YJ, Kim HJ. Feasibility and Safety of Transcutaneous Vagus Nerve Stimulation Paired with Notched Music Therapy for the Treatment of Chronic Tinnitus. J Audiol Otol. 2015 Dec;19(3):159-67. doi: 10.7874/jao.2015.19.3.159. Epub 2015 Dec 18.
- Background: PubMed 21158977Huston JM, Tracey KJ. The pulse of inflammation: heart rate variability, the cholinergic anti-inflammatory pathway and implications for therapy. J Intern Med. 2011 Jan;269(1):45-53. doi: 10.1111/j.1365-2796.2010.02321.x.
- Background: PubMed 19542466Huston JM, Rosas-Ballina M, Xue X, Dowling O, Ochani K, Ochani M, Yeboah MM, Chatterjee PK, Tracey KJ, Metz CN. Cholinergic neural signals to the spleen down-regulate leukocyte trafficking via CD11b. J Immunol. 2009 Jul 1;183(1):552-9. doi: 10.4049/jimmunol.0802684.
- Background: PubMed 18714026Huston JM, Wang H, Ochani M, Ochani K, Rosas-Ballina M, Gallowitsch-Puerta M, Ashok M, Yang L, Tracey KJ, Yang H. Splenectomy protects against sepsis lethality and reduces serum HMGB1 levels. J Immunol. 2008 Sep 1;181(5):3535-9. doi: 10.4049/jimmunol.181.5.3535.
- Background: PubMed 18669662Rosas-Ballina M, Ochani M, Parrish WR, Ochani K, Harris YT, Huston JM, Chavan S, Tracey KJ. Splenic nerve is required for cholinergic antiinflammatory pathway control of TNF in endotoxemia. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):11008-13. doi: 10.1073/pnas.0803237105. Epub 2008 Jul 31.
- Background: PubMed 17901837Huston JM, Gallowitsch-Puerta M, Ochani M, Ochani K, Yuan R, Rosas-Ballina M, Ashok M, Goldstein RS, Chavan S, Pavlov VA, Metz CN, Yang H, Czura CJ, Wang H, Tracey KJ. Transcutaneous vagus nerve stimulation reduces serum high mobility group box 1 levels and improves survival in murine sepsis. Crit Care Med. 2007 Dec;35(12):2762-8. doi: 10.1097/01.CCM.0000288102.15975.BA.
- Individual participant dataSharing planned: No. Information on live and deceased donors will be limited to that provided by the UNOS ID that does not contain any PHI.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ernesto P Molmenti, MD PhD MBA principal investigator
Northwell Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcutaneous electrical auricular vagus nerve stimulation (VNS) in people with Vagus Nerve Stimulation, run by Northwell Health at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: The study expired and was not renewed with the IRB). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Levels of blood inflammatory cytokines in kidney transplant recipients after transcutaneous auricular electrical vagus nerve stimulation. (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04256837, which also lists 18 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Dec 2022.