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Trial record 66 of 1728 for:    Recruiting, Not yet recruiting, Available Studies | Autoimmunity

VNS Prospective Neuromodulation of Autonomic, Immune and Gastrointestinal Systems (VNSAIG)

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ClinicalTrials.gov Identifier: NCT03953768
Recruitment Status : Not yet recruiting
First Posted : May 17, 2019
Last Update Posted : May 22, 2019
Sponsor:
Information provided by (Responsible Party):
Ian Mutchnick, University of Louisville

Brief Summary:
Vagal nerve stimulation is a neurosurgical procedure consisting of implantation of an impulse generator battery with leads placed into the vagus nerve in the neck. This procedure was FDA approved for epilepsy in the 1990s and is commonly performed as an outpatient surgery. The mechanism of efficacy is not well understood; however it is increasingly recognized that electrical stimulation of the vagus nerve may impact other organ systems in the body including the immune, gastrointestinal and autonomic systems. The primary objective of this study is to characterize the pre- and post-operative bowel habits and gut microbiome of patients implanted with vagal nerve stimulator (VNS) for epilepsy. Secondary objectives of this study include: (1) to characterize the pre- and post-operative autonomic profile, (2) characterize the pre- and post-operative immune profile, and (3) to elucidate whether gut microbiota changes are related to VNS efficacy for epilepsy.

Condition or disease Intervention/treatment Phase
Autoimmune Diseases Epilepsy Autonomic Dysfunction Inflammatory Bowel Diseases Device: Vagal nerve stimulation (VNS) Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Prospective single-arm with internal control group
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Prospective Non-randomized Single-arm Trial of Efferent Neuromodulation of Autonomic, Immune and Gastrointestinal Systems by VNS in the Epilepsy Population
Estimated Study Start Date : May 15, 2019
Estimated Primary Completion Date : May 14, 2020
Estimated Study Completion Date : May 15, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Epilepsy

Arm Intervention/treatment
Experimental: Patients undergoing device implantation
Patients undergoing device implantation with vagal nerve stimulator (VNS) for epilepsy
Device: Vagal nerve stimulation (VNS)
Implantation with vagal nerve stimulator for epilepsy
Other Name: Cyberonics VNS




Primary Outcome Measures :
  1. Metagenomic microbiome profile [ Time Frame: 1 year ]
    Stool and saliva specimens will be used to generate metagenomic profiles of gut flora populations. Pre- and post-VNS gut profiles will be compared. It is important to note that the genomic profile of all gut flora is the outcome, rather than the presence or absence of any specific type of bacteria.

  2. Bowel movement frequency [ Time Frame: 1 year ]
    A brief clinical questionnaire regarding the frequency and consistency of bowel movements will be administered. This will be done pre- and post-VNS implantation in each patient. Any medications to manage diarrhea and constipation will be carefully recorded as well as their efficacy.

  3. Abdominal pain [ Time Frame: 1 year ]
    A brief clinical questionnaire regarding the frequency, severity and location of abdominal pain. This will be done pre- and post-VNS implantation in each patient. Any medications to manage abdominal pain will be carefully recorded as well as their efficacy.

  4. Autonomic profile [ Time Frame: 1 year ]
    Heart rate variability as will be used as a biomarker for parasympathetic tone. Percent increase in post-operative heart rate variability from pre-operative baseline will be assessed.

  5. Immune Profile 1 - Flow cytometric profiling of cell populations [ Time Frame: 1 year ]
    One milliliter of whole blood from each subject will be aliquoted into separate tube and directly stained with fluorochrome-conjugated antibodies to investigate the cellular composition of the blood. Subtypes of lymphocytes, monocytes and granulocytes will be defined by set phenotypic marker expression

  6. Immune Profile 2 - Ex vivo stimulation of cells in whole blood [ Time Frame: 1 year ]
    Up to 10 ml of the whole blood will be cultured in 24-well tissue culture plates in the presence and absence of innate immune cell activators, such as TLR ligands, LPS, CpG ODN, poly I:C or flagellin, or adaptive immune activators such as anti-CD3/anti-CD28 beads, PHA or recall antigens. Culture supernatants and cells will be harvested at the needed time points and analyzed via MSD and qPCR, respectively.

  7. Inflammatory Profile 1 - Meso Scale Discovery (or MSD) analysis for pro-inflammatory cytokines/chemokines [ Time Frame: 1 year ]
    Serum electrochemiluminescence detection analysis of the following cytokines/chemokines: IFNg, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNFα. Units in Picograms/ml or Nanograms/ml depending on the specific chemokine/cytokine

  8. Inflammatory Profile 2 - Meso Scale Discovery (or MSD) analysis for metabolic hormones [ Time Frame: 1 year ]
    Serum electrochemiluminescence detection analysis of the following hormones: GLP-1, insulin, Glucagon, Leptin. All in picograms/mL.

  9. Inflammatory Profile 3 - Metabolomics for Short Chain Fatty acids (SCFAs) [ Time Frame: 1 year ]
    Short Chain Fatty Acids (SCFAs) in both feces and serum will be derivatized, extracted in organic solvent and analyzed using Gas chromatography-mass spectrometry (GC-MS) to determine the levels of short-chain fatty acids. To the microbial community SCFAs are a necessary waste product, required to balance redox equivalent production in the anaerobic environment of the gut. SCFAs are saturated aliphatic organic acids that consist of one to six carbons of which acetate (C2), propionate (C3), and butyrate (C4) are the most abundant (≥95%). Acetate, propionate, and butyrate are present in an approximate molar ratio of 60:20:20 and will be measured in picomoles/mL.

  10. Inflammatory Profile 4 - Intestinal inflammation and permeability markers [ Time Frame: 1 year ]
    sCD163 (nanograms/mL), sCD14 (micrograms/mL), CRP (mg/L), and I-FABP (picograms/mL) are markers of intestinal inflammation and permeability and will be measured using an enzyme-linked immunosorbent assay (ELISA) performed on cell-free supernatants such as plasma, serum and urine. The units of measurement


Secondary Outcome Measures :
  1. Epilepsy severity [ Time Frame: 1 year ]
    Patients will keep a log of seizure type, keeping careful track of the frequency of each type, how long each seizure lasts and what medical interventions are taken to stop each seizure.



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Ages Eligible for Study:   up to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Undergoing VNS implantation for the first time as a treatment for epilepsy
  • Documented follow up with a Louisville-based neurologist in the past 1 year or documented ability to follow to travel to Louisville for outpatient medical care

Exclusion Criteria:

  • Previous treatment with VNS
  • Current pregnancy (contraindication to surgery)
  • History of chemotherapy
  • Treatment with cholinergic or anticholinergic medication in the past month or during the study period
  • Pre-existing cardiac arrythmia or presence of cardiac pacemaker/defibrillator
  • Treatment with immunomodulator in the past month or during the study period
  • Treatment with steroids in the past month or during the study period
  • History of cancer

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): NCT03953768


Contacts
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Contact: Ian S Mutchnick, MD 502-629-5510 ianmutchnick@gmail.com
Contact: Meena A Thatikunta, MD 5132575926 meena.thatikunta@gmail.com

Sponsors and Collaborators
University of Louisville

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Responsible Party: Ian Mutchnick, Assistant Professor of Neurosurgery, University of Louisville
ClinicalTrials.gov Identifier: NCT03953768     History of Changes
Other Study ID Numbers: 19.0330
First Posted: May 17, 2019    Key Record Dates
Last Update Posted: May 22, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Ian Mutchnick, University of Louisville:
epilepsy
vagal
autoimmune
autonomic
inflammatory bowel disease
immune
Additional relevant MeSH terms:
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Autoimmune Diseases
Intestinal Diseases
Inflammatory Bowel Diseases
Epilepsy
Autonomic Nervous System Diseases
Primary Dysautonomias
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Gastrointestinal Diseases
Digestive System Diseases
Gastroenteritis
Immune System Diseases