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

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ClinicalTrials.gov Identifier: NCT03772717
Recruitment Status : Not yet recruiting
First Posted : December 11, 2018
Last Update Posted : September 6, 2019
Sponsor:
Collaborator:
Georgia Institute of Technology
Information provided by (Responsible Party):
Sumit Verma, Emory University

Brief Summary:
This study will be conducted at Children's Healthcare of Atlanta, in Atlanta, Georgia for a total duration of 24 months. The electrical neuromuscular stimulation device used in this study is the Vital EMS+, which has been used in multiple previous clinical studies for modulation of pain and has received FDA approval. A total of 10 study participants will be randomly assigned to one of two groups in the study: 5 will receive the standard of care treatment plus electrical neuromuscular stimulation and 5 will receive standard of care and devices that do not deliver electrical stimulation (sham device). Participants will be requested to deliver nVNS two times per day, at least five days per week in their home, for two years.

Condition or disease Intervention/treatment Phase
Chronic Inflammatory Demyelinating Polyneuropathy Device: Vital EMS+ Drug: Standard of Care Not Applicable

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. Treatment of CIDP involves chronic use of steroids, intravenous immunoglobulin (IVIG) and rarely plasma exchange (PLEX). Outcome measures such as patient reported motor disability scores, electrophysiology parameters, functional motor strength testing are available to look for interval change. Despite above mentioned treatments, the majority of patients have tremendous disease burden. There is a need for alternative/adjunctive therapies that can decrease chronic inflammation effectively and safely in pediatric CIDP patients.

Vagus nerve stimulation (VNS) 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 have demonstrated significant lifestyle benefits and reduced symptoms in these patients. Similar benefits of VNS have been observed in Crohn's patients. In these studies, patients are surgically implanted with a stimulator with 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 our 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 and 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 a brief duration 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.

Ten study participants will be randomly assigned to one of two groups in the study: those receiving the standard of care treatment plus electrical neuromuscular stimulation and those receiving the standard of care treatment and devices that do not deliver electrical stimulation (sham device). Participants will be requested to deliver nVNS two times per day, at least five days per week in their home, for two years.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Participants will be randomized to receive a device that delivers electrical neuromuscular stimulation or a sham device.
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: Non-invasive Vagus Nerve Stimulation (nVNS) in Pediatric Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
Estimated Study Start Date : October 2019
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : October 2020


Arm Intervention/treatment
Experimental: Vital EMS+
Participants will receive electrical neuromuscular stimulation via a Vital EMS+ device, along with the standard of care treatment.
Device: Vital EMS+
The nVNS study intervention will be delivered using a handheld electrical neuromuscular stimulator device (Vital EMS+). Participants will deliver nVNS twice per day for 60 minutes each time at least 5 days per week, for 2 years. The two electrodes for the device are placed on the left cervical (neck) region or on the left ear. 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.

Drug: Standard of Care
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:
  • intravenous immunoglobulin (IVIG)
  • plasma exchange (PLEX)

Sham Comparator: Sham device
Participants will receive a sham device that does not deliver electrical neuromuscular stimulation, along with the standard of care treatment.
Drug: Standard of Care
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:
  • intravenous immunoglobulin (IVIG)
  • plasma exchange (PLEX)




Primary Outcome Measures :
  1. Change in nerve conduction study distal latency [ Time Frame: Baseline, Month 12, Month 24 ]
    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 will stimulate 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.

  2. Change in nerve conduction study F wave latency [ Time Frame: Baseline, Month 12, Month 24 ]
    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 will stimulate 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.

  3. Change in nerve conduction study conduction velocity [ Time Frame: Baseline, Month 12, Month 24 ]
    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 will stimulate 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 (distance/time) and is often decreased in patients with CIDP as myelination is affected.

  4. Change in nerve conduction study conduction amplitude [ Time Frame: Baseline, Month 12, Month 24 ]
    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 will stimulate 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.

  5. Change in hand grip strength [ Time Frame: Baseline, Month 6, Month 12, Month 18, Month 24 ]
    Hand grip strength will be assessed with a Jamar Handheld Dynamometer with reference range (in kilograms and pounds) for children ages 5-18 years. Both right and left hand grip strength will be measured and the best of three attempts will be used for each hand. Increased hand strength is an indicator of effective treatment.

  6. Change in Rasch-built Overall Disability Scale (R-ODS) for CIDP [ Time Frame: Baseline, Month 6, Month 12, Month 18, Month 24 ]
    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 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.


Secondary Outcome Measures :
  1. Change in tumor necrosis factor (TNF)-α [ Time Frame: Baseline, Month 6, Month 12, Month 18, Month 24 ]
    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.

  2. Change in hepatocyte growth factor (HGF) [ Time Frame: Baseline, Month 6, Month 12, Month 18, Month 24 ]
    The impact of treatment on serum cytokine profiles will be assessed by measuring HGF. Serum cytokine levels will be statistically analyzed on a per patient basis, with each patient's baseline measurements used for comparison. HGF is elevated in CIDP patients and a decrease in HGF values is an indication of effective treatment.

  3. Change in macrophage inflammatory protein (MIP)-1β [ Time Frame: Baseline, Month 6, Month 12, Month 18, Month 24 ]
    The impact of treatment on serum cytokine profiles will be assessed by measuring MIP-1β. Serum cytokine levels will be statistically analyzed on a per patient basis, with each patient's baseline measurements used for comparison. MIP-1β is elevated in CIDP patients and a decrease in MIP-1β values is an indication of effective treatment.

  4. Change in interleukin (IL)-1β [ Time Frame: Baseline, Month 6, Month 12, Month 18, Month 24 ]
    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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Ages Eligible for Study:   5 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of CIDP based upon clinical/electrophysiological criteria
  • Patient should be on treatment for CIDP including IVIG and Steroids

Exclusion Criteria:

  • Patients will be excluded from the study if they have inherited polyneuropathy, such as Charcot Tooth Marie disease.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03772717


Contacts
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Contact: Sumit Verma, MD 404-785-9893 sumit.verma@emory.edu

Locations
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United States, Georgia
Childrens Healthcare of Atlanta Not yet recruiting
Atlanta, Georgia, United States, 30322
Contact: Sumit Verma, MD    404-785-9893    sumit.verma@emory.edu   
Sponsors and Collaborators
Emory University
Georgia Institute of Technology
Investigators
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Principal Investigator: Sumit Verma, MD Emory University
Principal Investigator: Robert Butera, PhD Georgia Institute of Technology

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Responsible Party: Sumit Verma, Assistant Professor, Emory University
ClinicalTrials.gov Identifier: NCT03772717     History of Changes
Other Study ID Numbers: IRB00098592
First Posted: December 11, 2018    Key Record Dates
Last Update Posted: September 6, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Keywords provided by Sumit Verma, Emory University:
Pediatrics
Vagus nerve stimulation
Additional relevant MeSH terms:
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Polyneuropathies
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Diseases
Polyradiculoneuropathy
Autoimmune Diseases of the Nervous System
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Immunoglobulins
Immunoglobulins, Intravenous
gamma-Globulins
Rho(D) Immune Globulin
Immunologic Factors
Physiological Effects of Drugs