Prospective Non-randomized Single-arm Trial of Efferent Neuromodulation Immune and Gastrointestinal Systems by VNS in the Epilepsy Population
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 8
- 主要终点
- Metagenomic microbiome profile
研究概览
简要总结
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 action 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 and gastrointestinal systems. Concrete characterization of the peripheral effects of VNS in human gut microbiome and immune systems will: (1) elucidate peripheral mechanism of action of chronic VNS therapy, (2) identify peripheral preoperative biomarker of VNS efficacy, and (3) create a foundation for research investigating new GM and IM-related disease indications for VNS.
The primary objective of this study is to characterize the pre- and post-operative oral and gut microbiome of patients implanted with vagal nerve stimulator (VNS) for epilepsy. Secondary objectives of this study include: (1) to characterize the pre-operative and post-operative immune profile of patients undergoing VNS implantation for epilepsy, (2) to elucidate whether oral and/or gut microbiota changes are related to VNS efficacy for epilepsy and (3) identification of a biomarker predicting VNS efficacy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 0 Years 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Metagenomic microbiome profile
时间窗: 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
时间窗: 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.
Bowel habits
时间窗: 1 year
A clinical bowel habits questionnaire will be administered at each study visit to determine changes in bowel habits pre and post operatively. Additionally, the Bristol stool scale will be assessed at each visit.
Immune Profile 1 - Flow cytometric profiling of cell populations
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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)
时间窗: 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
时间窗: 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
次要结局
- Epilepsy severity(1 year)
研究者
Ian Mutchnick
Assistant Professor of Neurosurgery
University of Louisville