Idiopathic Nephrotic SyndrometaVNSNCT04169776
Effect of Daily Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) on Proteinuria in Pediatric Patients With Idiopathic Nephrotic Syndrome
A study testing Transcutaneous Auricular Vagus Nerve (taVNS) stimulation in people with Idiopathic Nephrotic Syndrome and Frequently Relapsing Nephrotic Syndrome, run by Northwell Health at 1 site in United States.
Trial summary
This study evaluates the impact of transcutaneous auricular Vagus Nerve stimulation (taVNS) therapy on the incidence of nephrotic syndrome relapses in children with idiopathic nephrotic syndrome. Read more about this study
- Who is it for?
- Ages 2 to 21 years
- Conditions the study is for
- Idiopathic Nephrotic Syndrome, Frequently Relapsing Nephrotic Syndrome
- What is being tested?
- Transcutaneous Auricular Vagus Nerve (taVNS) stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2019to 1 Dec 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 2 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Subjects age 2-21 years of age
- eGFR > 60 ml/min/1.73 m2
- Diagnosis of idiopathic minimal change disease (clinical diagnosis or per biopsy)
- Prior history of remission of nephrotic syndrome within 4 weeks of initiation of steroid therapy (steroid sensitive nephrotic syndrome)
- 2 or more episodes of nephrotic syndrome relapses in a 6-month period or four or more episodes of nephrotic syndrome relapses in a 12-month period (relapse defined as 2+ proteinuria on first morning urine sample for three consecutive days or development of edema)
- In remission (no proteinuria - normal urine protein to creatinine ratio < 0.2) at the time of enrollment
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- Subjects age 2-21 years of age
- eGFR > 60 ml/min/1.73 m2
- Diagnosis idiopathic nephrotic syndrome (clinical diagnosis or per biopsy)
- Diagnosis of steroid-resistant nephrotic syndrome (symptoms or proteinuria not improved after 4 to 8 weeks of steroid therapy)
- Persistent proteinuria (first-morning urine protein to creatinine ratio > 0.2)
- At least 7 days since last dose of steroids
Who cannot join
- Subjects with nephrotic syndrome etiology other than idiopathic minimal change disease either biopsy-proven or by genetic testing
- Nephrotic syndrome due to secondary causes such as SLE, vasculitis, hepatitis, post-infectious etiology, medication-induced, etc.
- Subjects that did not achieve remission of nephrotic syndrome within 4 weeks of initiation of steroid therapy (steroid-resistant nephrotic syndrome)
- Subjects with urine protein to creatinine ratio of > 0.2 (not in remission)
- Subjects currently receiving any standing immunosuppressive therapy (mycophenolate mofetil, tacrolimus, rituximab - note: 1) previous exposure to these therapies does not exclude participation; 2) subjects with previous exposure to rituximab are eligible if B cells are replete)
- Subjects with a history of cardiac issues, including bradycardia, arrhythmias or structural abnormalities of the heart
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- Subjects with implantable electronic devices such as pacemakers, defibrillators, hearing aids, cochlear implants or deep brain stimulators
- Subjects with any other known inflammatory condition (IBD, SLE, etc.)
- Nephrotic syndrome due to secondary causes such as SLE, vasculitis, hepatitis, post-infectious etiology, medication-induced, etc.
- Subjects with a history of cardiac issues, including bradycardia, arrhythmias or structural abnormalities of the heart
- Subjects with implantable electronic devices such as pacemakers, defibrillators, hearing aids, cochlear implants or deep brain stimulators
- Subjects with any other known inflammatory condition (IBD, SLE, etc.)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Daily Transcutaneous Auricular Vagus Nerve (taVNS) Stimulation on Proteinuria in Pediatric Patients With Idiopathic Nephrotic Syndrome
This study evaluates the impact of transcutaneous auricular Vagus Nerve stimulation (taVNS) therapy on the incidence of nephrotic syndrome relapses in children with idiopathic nephrotic syndrome. Participants will perform taVNS 5 minutes a day for 6 months total, monitoring for signs of nephrotic syndrome relapse with both labwork and clinical symptoms.
Read the detailed description
Idiopathic nephrotic syndrome is defined as the development of proteinuria, edema, hypoalbuminemia, and hyperlipidemia often presenting in the pediatric population. The underlying pathogenesis of idiopathic nephrotic syndrome is poorly understood but likely involves dysregulation of the immune system, and the majority of patients respond to steroid therapy and other immunosuppressive therapy. Unfortunately, relapses are common, with at least one relapse occurring in up to 90% of patients. Frequently-relapsing patients may be exposed large amounts of steroids and other immunosuppressants with a multitude of adverse effects, while others may not even respond to these treatments. Therefore, novel therapies are being studied.
Vagus nerve stimulation is a novel therapy with the potential to treat inflammatory conditions via inhibition of cytokine release by the cholinergic anti-inflammatory pathway. The purpose of the proposed study is to investigate the use of vagus nerve stimulation in the prevention of nephrotic syndrome relapses and treatment of proteinuria in pediatric patients with idiopathic nephrotic syndrome.
Patients will be enrolled if they have frequently-relapsing idiopathic nephrotic syndrome or proteinuria which does not respond to steroid therapy. These patients will perform daily transcutaneous auricular Vagus Nerve stimulation (taVNS) therapy 5 minutes a day for a 6 month period and will be monitored for urine/bloodwork or clinical signs of nephrotic syndrome relapse.
- Being tested
- Transcutaneous Auricular Vagus Nerve (taVNS) stimulation
- Medical subject headings
- Nephrosis, Lipoid, Nephrotic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcutaneous Auricular Vagus Nerve (taVNS) stimulationDevice
Participants in this study will perform home transcutaneous auricular vagus nerve stimulation (taVNS) for 5 minutes a day for a 6-month period. The device that will be used is the commercially available Roscoe Medical TENS 7000 vagus nerve stimulator. The device will be attached to the Cymba Concha of the ear via an electrode ear clip. The intensity of the stimulation will be slowly increased and adjusted to individual tolerability for each treatment. TaVNS will be performed for 5 minutes daily for a period of 6 months.
| Study group | Role | What they receive |
|---|---|---|
| Steroid Sensitive Frequently-Relapsing Nephrotic Syndrome | Experimental | Individuals in this arm of the study will have to have a diagnosis of steroid sensitive frequently relapsing idiopathic nephrotic syndrome. They will receive transcutaneous auricular VNS (taVNS) performed for 5minutes every day for 6 months. The settings of the taVNS device will be individualized for each patient. Data will be collected on the the number of nephrotic syndrome relapses, the time between relapses, the time to remission once relapsed, and the level of proteinuria before and while using taVNS therapy. Receives: Device: Transcutaneous Auricular Vagus Nerve (taVNS) stimulation |
| Steroid Resistant Idiopathic Nephrotic Syndrome | Experimental | Individuals in this arm of the study will have to have a diagnosis of steroid resistant idiopathic nephrotic syndrome. They will receive transcutaneous auricular VNS (taVNS) performed for 5minutes every day for 6 months. The settings of the taVNS device will be individualized for each patient. Data will be collected on the the number of nephrotic syndrome relapses, the time between relapses, the time to remission once relapsed, and level of proteinuria before and while using taVNS therapy. Receives: Device: Transcutaneous Auricular Vagus Nerve (taVNS) stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of taVNS (Arms 1 and 2)
The endpoint of heart rate monitoring as a measure of safety of taVNS in this population was selected as this is the most concerning adverse effect of taVNS therapy. If there is no heart rate-related events during this study, it would further justify safe use of taVNS in the pediatric population.
Tolerability is an important measure in this study but is mostly a subjective measure. Therefore, patients who withdraw due to intolerability or report side effects which are deemed intolerable will aid in determining the feasibility of taVNS use in this population.
Measured: 6 months
Secondary outcomes (3)
Impact of taVNS on cytokine levels (Arms 1 and 2)
TaVNS has been shown in literature to have an anti-inflammatory effect when stimulating the vagus nerve. Several studies have found that cytokine levels are increased in nephrotic syndrome relapses as compared to levels when in remission. This endpoint provides a measure of the efficacy and compliance of taVNS use while also providing a marker for the effect of taVNS on the patient. Finally, if taVNS is shown to reduce the number of relapses while also suppressing cytokine levels, it may suggest a cytokine-associated etiology of idiopathic nephrotic syndrome.
Measured: 6 months
Impact of taVNS on number of nephrotic syndrome relapses, time to nephrotic syndrome relapses, and time to remission (Arm 1)
This outcome was chosen as an important measure of the efficacy of taVNS on patients with idiopathic nephrotic syndrome. A reduction in the number of relapses suggests that taVNS is a potential therapy for idiopathic nephrotic syndrome.
Measured: 6 months
Impact of taVNS on level of proteinuria (Arm 2)
The marker of disease progression and worsening outcomes is the level of proteinuria in patients with steroid-resistant idiopathic nephrotic syndrome. Measurement of the urine protein to creatinine level on a first morning sample is the most feasible and accurate measure of proteinuria in this patient population.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2019
- Study start1 Dec 2019
- Primary completion1 Mar 2021
- Study completion1 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Idiopathic Nephrotic SyndromeStudies 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
- Device feasibility
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- This study is a prospective cohort pilot study not formally classified as a specific trial phase. The study will involve two Arms, with 15 participants in each Arm of the study. Arm 1 will recruit patients with steroid-sensitive frequently-relapsing idiopathic nephrotic syndrome. Arm 2 will recruit patients with steroid-resistant idiopathic nephrotic syndrome. All participants in both Arms of the study will perform daily transcutaneous auricular vagus nerve stimulation (taVNS) therapy for 5 minutes each day. The study period will be 6 months. The participants will be monitored for labwork and clinical evidence of nephrotic syndrome relapse, comparing the number of relapses and level or proteinuria in the 6 months before starting taVNS therapy to number of relapses and level of proteinuria in the 6 month study period.
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwell Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Christine Sethna, MD, Principal investigator, Northwell Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04169776
- Sponsor's protocol ID
- 19-0861
- Acronym
- taVNS
- Status last verified
- Sep 2022
- First submitted
- 15 Nov 2019
- Last updated
- 28 Sep 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: Data will be shared if requested.
Publications
Merchant K, Zanos S, Datta-Chaudhuri T, Deutschman CS, Sethna CB. Transcutaneous auricular vagus nerve stimulation (taVNS) for the treatment of pediatric nephrotic syndrome: a pilot study. Bioelectron Med. 2022 Jan 26;8(1):1. doi: 10.1186/s42234-021-00084-6.
PubMed 35078538
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Daily Transcutaneous Auricular Vagus Nerve (taVNS) Stimulation on Proteinuria in Pediatric Patients With Idiopathic Nephrotic Syndrome
- ClinicalTrials.gov ID
- NCT04169776
- Acronym / sponsor ID
- taVNS / 19-0861
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Northwell HealthUniversity, hospital or other
- Study start
- 1 Dec 2019 (actual)
- Primary completion
- 1 Mar 2021 (actual)
- Study completion
- 1 Dec 2021 (actual)
- First posted
- 20 Nov 2019 (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.
This study evaluates the impact of transcutaneous auricular Vagus Nerve stimulation (taVNS) therapy on the incidence of nephrotic syndrome relapses in children with idiopathic nephrotic syndrome. Participants will perform taVNS 5 minutes a day for 6 months total, monitoring for signs of nephrotic syndrome relapse with both labwork and clinical symptoms.
Detailed description
Idiopathic nephrotic syndrome is defined as the development of proteinuria, edema, hypoalbuminemia, and hyperlipidemia often presenting in the pediatric population. The underlying pathogenesis of idiopathic nephrotic syndrome is poorly understood but likely involves dysregulation of the immune system, and the majority of patients respond to steroid therapy and other immunosuppressive therapy. Unfortunately, relapses are common, with at least one relapse occurring in up to 90% of patients. Frequently-relapsing patients may be exposed large amounts of steroids and other immunosuppressants with a multitude of adverse effects, while others may not even respond to these treatments. Therefore, novel therapies are being studied.
Vagus nerve stimulation is a novel therapy with the potential to treat inflammatory conditions via inhibition of cytokine release by the cholinergic anti-inflammatory pathway. The purpose of the proposed study is to investigate the use of vagus nerve stimulation in the prevention of nephrotic syndrome relapses and treatment of proteinuria in pediatric patients with idiopathic nephrotic syndrome.
Patients will be enrolled if they have frequently-relapsing idiopathic nephrotic syndrome or proteinuria which does not respond to steroid therapy. These patients will perform daily transcutaneous auricular Vagus Nerve stimulation (taVNS) therapy 5 minutes a day for a 6 month period and will be monitored for urine/bloodwork or clinical signs of nephrotic syndrome relapse.
Study design
- Primary purpose
- Device feasibility
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This study is a prospective cohort pilot study not formally classified as a specific trial phase. The study will involve two Arms, with 15 participants in each Arm of the study. Arm 1 will recruit patients with steroid-sensitive frequently-relapsing idiopathic nephrotic syndrome. Arm 2 will recruit patients with steroid-resistant idiopathic nephrotic syndrome. All participants in both Arms of the study will perform daily transcutaneous auricular vagus nerve stimulation (taVNS) therapy for 5 minutes each day. The study period will be 6 months. The participants will be monitored for labwork and clinical evidence of nephrotic syndrome relapse, comparing the number of relapses and level or proteinuria in the 6 months before starting taVNS therapy to number of relapses and level of proteinuria in the 6 month study period.
| Arm | Type | Receives |
|---|---|---|
| Steroid Sensitive Frequently-Relapsing Nephrotic Syndrome | Experimental | Device: Transcutaneous Auricular Vagus Nerve (taVNS) stimulationIndividuals in this arm of the study will have to have a diagnosis of steroid sensitive frequently relapsing idiopathic nephrotic syndrome. They will receive transcutaneous auricular VNS (taVNS) performed for 5minutes every day for 6 months. The settings of the taVNS device will be individualized for each patient. Data will be collected on the the number of nephrotic syndrome relapses, the time between relapses, the time to remission once relapsed, and the level of proteinuria before and while using taVNS therapy. |
| Steroid Resistant Idiopathic Nephrotic Syndrome | Experimental | Device: Transcutaneous Auricular Vagus Nerve (taVNS) stimulationIndividuals in this arm of the study will have to have a diagnosis of steroid resistant idiopathic nephrotic syndrome. They will receive transcutaneous auricular VNS (taVNS) performed for 5minutes every day for 6 months. The settings of the taVNS device will be individualized for each patient. Data will be collected on the the number of nephrotic syndrome relapses, the time between relapses, the time to remission once relapsed, and level of proteinuria before and while using taVNS therapy. |
Who may qualify
- Ages
- 2 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (12 listed)
- Subjects age 2-21 years of age
- eGFR > 60 ml/min/1.73 m2
- Diagnosis of idiopathic minimal change disease (clinical diagnosis or per biopsy)
- Prior history of remission of nephrotic syndrome within 4 weeks of initiation of steroid therapy (steroid sensitive nephrotic syndrome)
- 2 or more episodes of nephrotic syndrome relapses in a 6-month period or four or more episodes of nephrotic syndrome relapses in a 12-month period (relapse defined as 2+ proteinuria on first morning urine sample for three consecutive days or development of edema)
Key exclusion criteria (12 listed)
- Subjects with nephrotic syndrome etiology other than idiopathic minimal change disease either biopsy-proven or by genetic testing
- Nephrotic syndrome due to secondary causes such as SLE, vasculitis, hepatitis, post-infectious etiology, medication-induced, etc.
- Subjects that did not achieve remission of nephrotic syndrome within 4 weeks of initiation of steroid therapy (steroid-resistant nephrotic syndrome)
- Subjects with urine protein to creatinine ratio of > 0.2 (not in remission)
- Subjects currently receiving any standing immunosuppressive therapy (mycophenolate mofetil, tacrolimus, rituximab - note: 1) previous exposure to these therapies does not exclude participation; 2) subjects with previous exposure to rituximab are eligible if B cells are replete)
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 Auricular Vagus Nerve (taVNS) stimulationParticipants in this study will perform home transcutaneous auricular vagus nerve stimulation (taVNS) for 5 minutes a day for a 6-month period. The device that will be used is the commercially available Roscoe Medical TENS 7000 vagus nerve stimulator. The device will be attached to the Cymba Concha of the ear via an electrode ear clip. The intensity of the stimulation will be slowly increased and adjusted to individual tolerability for each treatment. TaVNS will be performed for 5 minutes daily for a period of 6 months. | Device | Steroid Resistant Idiopathic Nephrotic Syndrome, Steroid Sensitive Frequently-Relapsing Nephrotic Syndrome |
Primary outcome
Safety and tolerability of taVNS (Arms 1 and 2)
Time frame: 6 months
The endpoint of heart rate monitoring as a measure of safety of taVNS in this population was selected as this is the most concerning adverse effect of taVNS therapy. If there is no heart rate-related events during this study, it would further justify safe use of taVNS in the pediatric population. Tolerability is an important measure in this study but is mostly a subjective measure. Therefore, patients who withdraw due to intolerability or report side effects which are deemed intolerable will aid in determining the feasibility of taVNS use in this population.
3 secondary outcomes
Impact of taVNS on cytokine levels (Arms 1 and 2)
Time frame: 6 months
Impact of taVNS on number of nephrotic syndrome relapses, time to nephrotic syndrome relapses, and time to remission (Arm 1)
Time frame: 6 months
Impact of taVNS on level of proteinuria (Arm 2)
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2022.
- Derived from this study: PubMed 35078538Merchant K, Zanos S, Datta-Chaudhuri T, Deutschman CS, Sethna CB. Transcutaneous auricular vagus nerve stimulation (taVNS) for the treatment of pediatric nephrotic syndrome: a pilot study. Bioelectron Med. 2022 Jan 26;8(1):1. doi: 10.1186/s42234-021-00084-6.
- Individual participant dataSharing planned: Yes. Data will be shared if requested.
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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.
Christine Sethna, MD 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 Auricular Vagus Nerve (taVNS) stimulation in people with Idiopathic Nephrotic Syndrome and Frequently Relapsing Nephrotic Syndrome, 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 12 inclusion and 12 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: finished, as of the sponsor's last update on 28 Sep 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. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Safety and tolerability of taVNS (Arms 1 and 2) (time frame: 6 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 NCT04169776, which also lists 1 linked publication.
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 28 Sep 2022.