- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03953768
VNS Prospective Neuromodulation of Autonomic, Immune and Gastrointestinal Systems (VNSAIG)
August 4, 2023 updated by: Ian Mutchnick, University of Louisville
Prospective Non-randomized Single-arm Trial of Efferent Neuromodulation of Autonomic, Immune and Gastrointestinal Systems by VNS in the Epilepsy Population
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.
Study Overview
Status
Recruiting
Intervention / Treatment
Study Type
Interventional
Enrollment (Estimated)
30
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Ian S Mutchnick, MD
- Phone Number: 502-629-5510
- Email: ianmutchnick@gmail.com
Study Contact Backup
- Name: Meena A Thatikunta, MD
- Phone Number: 5132575926
- Email: meena.thatikunta@gmail.com
Study Locations
-
-
Kentucky
-
Louisville, Kentucky, United States, 40202
- Recruiting
- University of Louisville
-
Contact:
- Meena Vessell, MD
- Phone Number: 513-257-5926
- Email: meena.thatikunta@louisville.edu
-
Louisville, Kentucky, United States, 40202
- Not yet recruiting
- Norton Healthcare
-
Contact:
- Ian S Mutchnick
- Phone Number: 502-322-5714
- Email: ianmutchnick@gmail.com
-
Contact:
- Nora Howerton
- Phone Number: 16543 5025831697
- Email: nora.howerton@nortonhealthcare.org
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
1 second to 60 years (Child, Adult)
Accepts Healthy Volunteers
Yes
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Patients undergoing device implantation
Patients undergoing device implantation with vagal nerve stimulator (VNS) for epilepsy
|
Implantation with vagal nerve stimulator for epilepsy
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
1 year
|
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.
|
1 year
|
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.
|
1 year
|
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
|
1 year
|
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.
|
1 year
|
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
|
1 year
|
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.
|
1 year
|
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.
|
1 year
|
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
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
1 year
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 1, 2021
Primary Completion (Estimated)
December 14, 2025
Study Completion (Estimated)
December 14, 2026
Study Registration Dates
First Submitted
April 15, 2019
First Submitted That Met QC Criteria
May 14, 2019
First Posted (Actual)
May 17, 2019
Study Record Updates
Last Update Posted (Actual)
August 7, 2023
Last Update Submitted That Met QC Criteria
August 4, 2023
Last Verified
August 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 19.0330
- 5P20GM113226 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
Yes
product manufactured in and exported from the U.S.
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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