Clinical trial NCT03953768: VNS Prospective Neuromodulation of Immune and Gastrointestinal Systems
Official title: Prospective Non-randomized Single-arm Trial of Efferent Neuromodulation Immune and Gastrointestinal Systems by VNS in the Epilepsy Population
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Autoimmune Diseases
Epilepsy
Autonomic Dysfunction
Inflammatory Bowel Diseases
Keywords: epilepsy
vagal
autoimmune
autonomic
inflammatory bowel disease
immune
Lead sponsor: University of Louisville
Sponsor class: OTHER
Collaborators: name: LivaNova
name: Norton Foundation
First posted: 2019-05-17
Enrollment: 30
Sex: ALL
Minimum age (years): 0
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Prospective single-arm with internal control group
Primary purpose: OTHER

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 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.


Eligibility criteria: Inclusion criteria:

1. Undergoing VNS implantation for the first time as a treatment for epilepsy and
2. Documented follow up with a Louisville-based neurologist in the past 1 year. If at the University of Utah or Baylor University documented ability to travel to their corresponding neurologist.
3. Documented ability to travel to Louisville for outpatient medical care. If at the University of Utah or Baylor University documented ability to travel to their facilities.

Exclusion criteria:

1. Previous treatment with VNS (other than the one implanted for this study)
2. Current pregnancy (contraindication to surgery)
3. Active infection
4. History of cancer or treatment with chemotherapy
5. History of autoimmune disease: Patients who received high effect anticholinergic medication within 30 days of enrollment will be excluded, whereas moderate to low effect anticholinergic medication will be discussed with and decided by the PI.
6. If any high effect anticholinergic medication is started after enrollment, it will be the PI's decision to drop or postpone the corresponding visit or exclude the patient entirely.
7. Patients who received high effect corticosteroids within 30 days of enrollment will be excluded, whereas moderate to low effect corticosteroids will be discussed with and decided by the PI.
8. If any high effect corticosteroid is started after enrollment, it will be the PI's decision to drop or postpone the corresponding visit or exclude the patient entirely.
9. Treatment with antiarrhythmic or (heart) rate controlling medication,
10. Pre-existing cardiac arrhythmia or presence of cardiac pacemaker / defibrillator

Primary outcomes:
measure: Metagenomic microbiome profile
timeFrame: 1 year
measure: Bowel movement frequency
timeFrame: 1 year
measure: Bowel habits
timeFrame: 1 year
measure: Immune Profile 1 - Flow cytometric profiling of cell populations
timeFrame: 1 year
measure: Immune Profile 2 - Ex vivo stimulation of cells in whole blood
timeFrame: 1 year
measure: Inflammatory Profile 1 - Meso Scale Discovery (or MSD) analysis for pro-inflammatory cytokines/chemokines
timeFrame: 1 year
measure: Inflammatory Profile 2 - Meso Scale Discovery (or MSD) analysis for metabolic hormones
timeFrame: 1 year
measure: Inflammatory Profile 3 - Metabolomics for Short Chain Fatty acids (SCFAs)
timeFrame: 1 year
measure: Inflammatory Profile 4 - Intestinal inflammation and permeability markers
timeFrame: 1 year
Secondary outcomes:
measure: Epilepsy severity
timeFrame: 1 year
Other outcomes:
Locations:
city: Louisville
country: United States
facility: Norton Healthcare
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Hospital/University of Utah
state: Utah
Study officials:
References: