VNS Prospective Neuromodulation of Autonomic, Immune and Gastrointestinal Systems (VNSAIG)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03953768|
Recruitment Status : Not yet recruiting
First Posted : May 17, 2019
Last Update Posted : May 22, 2019
|Condition or disease||Intervention/treatment||Phase|
|Autoimmune Diseases Epilepsy Autonomic Dysfunction Inflammatory Bowel Diseases||Device: Vagal nerve stimulation (VNS)||Not Applicable|
|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)|
|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|
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
- 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.
- 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.
- 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.
- 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.
- 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
- 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.
- 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
- 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.
- 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.
- 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
- 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.
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
|Contact: Ian S Mutchnick, MDfirstname.lastname@example.org|
|Contact: Meena A Thatikunta, MDemail@example.com|