- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03772717
Non-invasive Vagus Nerve Stimulation (nVNS) in Pediatric Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
Study Overview
Status
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Sumit Verma, MD
- Phone Number: 404-785-9893
- Email: sumit.verma@emory.edu
Study Locations
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Georgia
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Atlanta, Georgia, United States, 30322
- Children's Healthcare of Atlanta, Center for Advanced Pediatrics
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: 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.
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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 Names:
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).
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Nerve Conduction Study - Distal Latency
Time Frame: Baseline, Month 12, Month 24
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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.
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Baseline, Month 12, Month 24
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Nerve Conduction Study - F Wave Latency
Time Frame: Baseline, Month 12, Month 24
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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.
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Baseline, Month 12, Month 24
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Nerve Conduction Study - Conduction Velocity
Time Frame: Baseline, Month 12, Month 24
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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.
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Baseline, Month 12, Month 24
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Nerve Conduction Study - Conduction Amplitude
Time Frame: Baseline, Month 12, Month 24
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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.
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Baseline, Month 12, Month 24
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Hand Grip Strength
Time Frame: Baseline, Month 6, Month 12, Month 18, Month 24
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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.
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Baseline, Month 6, Month 12, Month 18, Month 24
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Rasch-built Overall Disability Scale (R-ODS) for CIDP Score
Time Frame: Baseline, Month 6, Month 12, Month 18, Month 24
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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.
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Baseline, Month 6, Month 12, Month 18, Month 24
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Tumor Necrosis Factor (TNF)-α
Time Frame: Baseline, Month 6, Month 12, Month 18, Month 24
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The impact of treatment on serum cytokine profiles will be assessed by measuring TNF-α.
Serum cytokine levels will be statistically analyzed on a per patient basis, with each patient's baseline measurements used for comparison.
TNF-α is elevated in CIDP patients and a decrease in serum TNF-α is an indication of effective treatment.
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Baseline, Month 6, Month 12, Month 18, Month 24
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Interleukin (IL)-1β
Time Frame: Baseline, Month 6, Month 12, Month 18, Month 24
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The impact of treatment on serum cytokine profiles will be assessed by measuring IL-1β.
Serum cytokine levels will be statistically analyzed on a per patient basis, with each patient's baseline measurements used for comparison.
IL-1β is elevated in CIDP patients and a decrease in IL-1β values is an indication of effective treatment.
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Baseline, Month 6, Month 12, Month 18, Month 24
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Sumit Verma, MD, Emory University
- Principal Investigator: Robert Butera, PhD, Georgia Institute of Technology
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Nervous System Diseases
- Immune System Diseases
- Autoimmune Diseases of the Nervous System
- Demyelinating Diseases
- Autoimmune Diseases
- Disease Attributes
- Neuromuscular Diseases
- Peripheral Nervous System Diseases
- Polyradiculoneuropathy
- Chronic Disease
- Polyneuropathies
- Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
- Physiological Effects of Drugs
- Immunologic Factors
- Immunoglobulins
- Immunoglobulins, Intravenous
- gamma-Globulins
- Rho(D) Immune Globulin
Other Study ID Numbers
- IRB00098592
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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