Effect of Daily Transcutaneous Auricular Vagus Nerve (taVNS) Stimulation on Proteinuria in Pediatric Patients With Idiopathic Nephrotic Syndrome
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Safety and tolerability of taVNS (Arms 1 and 2)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Device Feasibility
- 盲法
- None
盲法说明
This study design was chosen as it is the most realistic and practical design for this pilot study. There is no blinding or masking in this pilot study.
入排标准
- 年龄范围
- 2 Years 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •Inclusion Criteria (Arm 2):
- •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
排除标准
- •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
- •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.)
- •Exclusion Criteria (Arm 2):
- •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.)
研究组 & 干预措施
Steroid Sensitive Frequently-Relapsing Nephrotic Syndrome
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.
干预措施: Transcutaneous Auricular Vagus Nerve (taVNS) stimulation (Device)
Steroid Resistant Idiopathic Nephrotic Syndrome
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.
干预措施: Transcutaneous Auricular Vagus Nerve (taVNS) stimulation (Device)
结局指标
主要结局
Safety and tolerability of taVNS (Arms 1 and 2)
时间窗: 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.
次要结局
- Impact of taVNS on level of proteinuria (Arm 2)(6 months)
- Impact of taVNS on cytokine levels (Arms 1 and 2)(6 months)
- Impact of taVNS on number of nephrotic syndrome relapses, time to nephrotic syndrome relapses, and time to remission (Arm 1)(6 months)