Clinical trial NCT03772717: Non-invasive Vagus Nerve Stimulation (nVNS) in Pediatric Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
Official title: Non-invasive Vagus Nerve Stimulation (nVNS) in Pediatric Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Chronic Inflammatory Demyelinating Polyneuropathy
Keywords: Pediatrics
Vagus nerve stimulation
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Georgia Institute of Technology
First posted: 2018-12-11
Enrollment: 2
Sex: ALL
Minimum age (years): 5
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Participants will be requested to deliver non-invasive vagus nerve stimulation (nVNS) two times per day, at least five days per week. Participants will be followed for two years with nVNS as an adjunctive therapy to the standard of care therapy for chronic inflammatory demyelinating polyneuropathy (CIDP).

Detailed description: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a chronic immune-mediated disease of the peripheral sensory motor nerves characterized by motor weakness, sensory loss, muscle wasting and loss of motor ability. The majority of CIDP cases are idiopathic with insidious onset, relapsing remitting course, and a prolonged clinical course (over years). CIDP incidence is unknown in pediatric population, however, it is a rare treatable cause of neuromuscular weakness in children. Treatment of CIDP involves chronic use of steroids, intravenous immunoglobulin (IVIG) and, rarely, plasma exchange (PLEX). Despite above mentioned treatments the majority of patients continue to have tremendous disease burden. There is a need for alternative or adjunctive therapies that can decrease chronic inflammation effectively and safely in pediatric CIDP patients.

Vagus nerve stimulation has received significant scientific and clinical attention and has been shown to effectively reduce systemic inflammation. Results from early clinical trials for treatment of Rheumatoid Arthritis (RA) have demonstrated significant lifestyle benefits and reduced symptoms in RA patients. Similar benefits of VNS have been observed in Crohn's disease patients. In these studies, patients are surgically implanted with a stimulator and electrodes directly on the nerve. Preliminary results have demonstrated safety and efficacy in patients that previously were unresponsive to traditional pharmacological therapies. Unfortunately, surgical implantation of a device is difficult and costly.

Recent investigations have significantly increased the understanding of non-invasive vagus nerve stimulation (nVNS). Compared to traditional implanted vagus nerve stimulation devices, nVNS uses electrodes placed on the skin surface to stimulate the vagus nerve. nVNS has shown promise in animal and human models to reduce chronic inflammation in multiple disease states. By delivering electrical pulses at the skin surface above the vagus nerve, neural pathways involved in regulating systemic inflammation are activated. Using a handheld device, patients apply brief durations of stimulation multiple times per day to achieve therapeutic benefit. nVNS is currently FDA approved for clinical use in the treatment of migraines and cluster headaches, with on-going clinical studies on epilepsy and systemic inflammation. Preliminary published results have demonstrated significant therapeutic benefit to the patients with minimal side-effects such as a feeling of paresthesia at the site of the electrodes which subsides after turning the stimulation off.

Study participants will administer non-invasive vagus nerve stimulation (nVNS) two times per day, at least five days per week, as an adjunctive therapy to their standard of care treatment for CIDP. Participants will be followed for two years to understand the impact of nVNS on CIDP symptoms and the compliance with nVNS therapies in pediatric patients.

Eligibility criteria: Inclusion criteria:

* Diagnosis of CIDP based upon clinical/electrophysiological criteria
* On treatment for CIDP including IVIG and/ or steroids/plasma exchange

Exclusion criteria:

* Inherited polyneuropathy, such as Charcot Tooth Marie disease
* Abnormal baseline EKG, heart disease, epilepsy, pregnancy, multiple sclerosis and diabetes mellitus

Primary outcomes:
measure: Nerve Conduction Study - Distal Latency
timeFrame: Baseline, Month 12, Month 24
measure: Nerve Conduction Study - F Wave Latency
timeFrame: Baseline, Month 12, Month 24
measure: Nerve Conduction Study - Conduction Velocity
timeFrame: Baseline, Month 12, Month 24
measure: Nerve Conduction Study - Conduction Amplitude
timeFrame: Baseline, Month 12, Month 24
measure: Hand Grip Strength
timeFrame: Baseline, Month 6, Month 12, Month 18, Month 24
measure: Rasch-built Overall Disability Scale (R-ODS) for CIDP Score
timeFrame: Baseline, Month 6, Month 12, Month 18, Month 24
Secondary outcomes:
measure: Tumor Necrosis Factor (TNF)-α
timeFrame: Baseline, Month 6, Month 12, Month 18, Month 24
measure: Interleukin (IL)-1β
timeFrame: Baseline, Month 6, Month 12, Month 18, Month 24
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta, Center for Advanced Pediatrics
state: Georgia
Study officials:
affiliation: Emory University
name: Sumit Verma, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Georgia Institute of Technology
name: Robert Butera, PhD
role: PRINCIPAL_INVESTIGATOR
References: