Non-invasive Vagus Nerve Stimulation (nVNS) in Pediatric Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

NCT ID: NCT03772717

Last Updated: 2023-07-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-22
• Study Completion Date: 2022-06-30

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.

Conditions

Chronic Inflammatory Demyelinating Polyneuropathy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Non-invasive vagus nerve stimulation (nVNS)

Participants will use the electrical neuromuscular stimulator device, VitalStim 400, which has been used in previous clinical studies for modulation of pain and has received FDA approval. Participants will also continue to take their standard of care medication.

Group Type: EXPERIMENTAL

Non-invasive vagus nerve stimulation (nVNS)

Intervention Type: DEVICE

The nVNS study intervention will be delivered using a handheld electrical neuromuscular stimulator device (VitalStim 400). Participants will deliver nVNS twice per day for 60 minutes each time at least 5 days per week. The two electrodes for the device will be placed on the subjects left cervical (neck) region. Parents will be trained on where to place electrodes, how to ensure that the electrodes make a good contact with the skin, and how to set the stimulation parameters. The stimulation frequency (number of pulses) and amplitude (amount of current) will be set during the initial baseline session in the clinic at a level that prevents discomfort and does not impact cardiorespiratory parameters. The stimulator will be placed in a comfortable position, such as next to the pillow. The stimulators are battery-powered and allow configuration of the stimulation parameters to the comfort of the patient.

Standard of care treatment

Intervention Type: OTHER

Patients will be asked to continue their standard medication regimens which include in most cases will involve 3 weekly infusions of intravenous immunoglobulin (IVIG) (1 gm/kg) and rarely plasma exchange (PLEX).

Interventions

Non-invasive vagus nerve stimulation (nVNS)

The nVNS study intervention will be delivered using a handheld electrical neuromuscular stimulator device (VitalStim 400). Participants will deliver nVNS twice per day for 60 minutes each time at least 5 days per week. The two electrodes for the device will be placed on the subjects left cervical (neck) region. Parents will be trained on where to place electrodes, how to ensure that the electrodes make a good contact with the skin, and how to set the stimulation parameters. The stimulation frequency (number of pulses) and amplitude (amount of current) will be set during the initial baseline session in the clinic at a level that prevents discomfort and does not impact cardiorespiratory parameters. The stimulator will be placed in a comfortable position, such as next to the pillow. The stimulators are battery-powered and allow configuration of the stimulation parameters to the comfort of the patient.

Intervention Type: DEVICE

Standard of care treatment

Patients will be asked to continue their standard medication regimens which include in most cases will involve 3 weekly infusions of intravenous immunoglobulin (IVIG) (1 gm/kg) and rarely plasma exchange (PLEX).

Intervention Type: OTHER

Other Intervention Names

VitalStim 400; intravenous immunoglobulin (IVIG); plasma exchange (PLEX)

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

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Georgia Institute of Technology

OTHER

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Sumit Verma

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sumit Verma, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Robert Butera, PhD

Role: PRINCIPAL_INVESTIGATOR

Georgia Institute of Technology

Locations

Children's Healthcare of Atlanta, Center for Advanced Pediatrics

Atlanta, Georgia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRB00098592

Identifier Type: -

Identifier Source: org_study_id