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

Chronic Inflammatory Demyelinating Polyneuropathy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03772717
• Other study ID #: IRB00098592
• Status: Terminated
• Phase: N/A
• Start date: February 22, 2022
• Est. completion date: June 30, 2022

Study information

• Verified date: June 2023
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: June 30, 2022
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 21 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Inflammatory Demyelinating Polyneuropathy
• Polyneuropathies
• Polyradiculoneuropathy, Chronic Inflammatory Demyelinating

Intervention

Device:
• 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.

Other:
• 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).

Locations

Country	Name	City	State
United States	Children's Healthcare of Atlanta, Center for Advanced Pediatrics	Atlanta	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Emory University	Georgia Institute of Technology

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Nerve Conduction Study - Distal Latency	Motor nerve conduction studies are used to examine conduction of electrical impulses along nerves. Electrodes are placed on the skin in specific areas to evaluate peripheral nerves. An electrode stimulates a nerve while the receiving site records how well electrical impulses are being conducted along the nerve. Latency is the time it takes in milliseconds (ms) for the electrical impulse to travel to the site receiving the stimulation.	Baseline, Month 12, Month 24
Primary	Nerve Conduction Study - F Wave Latency	Motor nerve conduction studies are used to examine conduction of electrical impulses along nerves. Electrodes are placed on the skin in specific areas to evaluate peripheral nerves. An electrode stimulates a nerve while the receiving site records how well electrical impulses are being conducted along the nerve. F wave latency is the time it takes in milliseconds (ms) for an electrical signal to travel from the stimulating electrode to the distal muscle and back to the stimulating site. F waves are used to assess polyneuropathy and F wave latency can be extended or even absent in persons with CIDP.	Baseline, Month 12, Month 24
Primary	Nerve Conduction Study - Conduction Velocity	Motor nerve conduction studies are used to examine conduction of electrical impulses along nerves. Electrodes are placed on the skin in specific areas to evaluate peripheral nerves. An electrode stimulates a nerve while the receiving site records how well electrical impulses are being conducted along the nerve. Conduction velocity measures the rate of impulse conduction in meters per second (m/s) and is often decreased in patients with CIDP as myelination is affected.	Baseline, Month 12, Month 24
Primary	Nerve Conduction Study - Conduction Amplitude	Motor nerve conduction studies are used to examine conduction of electrical impulses along nerves. Electrodes are placed on the skin in specific areas to evaluate peripheral nerves. An electrode stimulates a nerve while the receiving site records how well electrical impulses are being conducted along the nerve. Conduction amplitude is the size of the response to electrical stimulation, measured in millivolts (mV). Reduced amplitude indicates axon loss.	Baseline, Month 12, Month 24
Primary	Hand Grip Strength	Hand grip strength is assessed with a Jamar Handheld Dynamometer for children ages 5-18 years and measures strength in kilograms (kg). Both right and left hand grip strength were measured and the best of three attempts were used for each hand. Increased hand strength is an indicator of effective treatment.	Baseline, Month 6, Month 12, Month 18, Month 24
Primary	Rasch-built Overall Disability Scale (R-ODS) for CIDP Score	The Rasch-built Overall Disability Scale (R-ODS) used for those with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and gammopathy-related polyneuropathy (MGUSP) is a 24-item scale asking respondents to rate how greatly polyneuropathy impacts activities. Responses are given on a scale of 0 to 2 where 0 indicates it is not possible for the respondent to perform the task and 2 means that the task can be performed without difficulty. Total scores range from 0 to 48 and higher scores indicate greater ability to perform daily and social tasks.	Baseline, Month 6, Month 12, Month 18, Month 24
Secondary	Tumor Necrosis Factor (TNF)-a	The impact of treatment on serum cytokine profiles will be assessed by measuring TNF-a. Serum cytokine levels will be statistically analyzed on a per patient basis, with each patient's baseline measurements used for comparison. TNF-a is elevated in CIDP patients and a decrease in serum TNF-a is an indication of effective treatment.	Baseline, Month 6, Month 12, Month 18, Month 24
Secondary	Interleukin (IL)-1ß	The impact of treatment on serum cytokine profiles will be assessed by measuring IL-1ß. Serum cytokine levels will be statistically analyzed on a per patient basis, with each patient's baseline measurements used for comparison. IL-1ß is elevated in CIDP patients and a decrease in IL-1ß values is an indication of effective treatment.	Baseline, Month 6, Month 12, Month 18, Month 24