Autoimmune DiseasesVNS-IGNCT03953768
VNS Prospective Neuromodulation of Immune and Gastrointestinal Systems
A study testing Vagal nerve stimulation (VNS) in people with Autoimmune Diseases and Epilepsy, run by University of Louisville at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 0 to 60 years
- Conditions the study is for
- Autoimmune Diseases, Epilepsy, Autonomic Dysfunction
- What is being tested?
- Vagal nerve stimulation (VNS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 4 sitesUnited States
- Study dates
- 1 Apr 2021to 31 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Undergoing VNS implantation for the first time as a treatment for epilepsy and
- 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.
- 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.
Who cannot join
- Previous treatment with VNS (other than the one implanted for this study)
- Current pregnancy (contraindication to surgery)
- Active infection
- History of cancer or treatment with chemotherapy
- 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.
- 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.
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- 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.
- 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.
- Treatment with antiarrhythmic or (heart) rate controlling medication,
- Pre-existing cardiac arrhythmia or presence of cardiac pacemaker / defibrillator
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Meena A Vessell, MD contact
United States4 sites, 3 recruiting
- Active, not recruiting
Texas Children's Hospital
Houston, Texas, 77030
- Not yet recruiting
Norton Healthcare
Louisville, Kentucky, 40202
Ian S Mutchnick, 5023225714, ianmutchnick@gmail.com
Nora Howerton, 5025831697 ext. 16543, nora.howerton@nortonhealthcare.org
- Recruiting
University of Louisville
Louisville, Kentucky, 40202
Ian Mutchnick, MD, 5026295512, ianmutchnick@gmail.com
- Recruiting
Primary Children's Hospital/University of Utah
Salt Lake City, Utah, 84113
Rob Bollo, MD, (801) 662-1000, robert.bollo@hsc.utah.edu
Rob Bollo, MD
About this study
Official title: Prospective Non-randomized Single-arm Trial of Efferent Neuromodulation 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 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.
- Being tested
- Vagal nerve stimulation (VNS)
- Keywords
- epilepsy, vagal, autoimmune, autonomic, inflammatory bowel disease, immune
- Medical subject headings
- Autoimmune Diseases, Epilepsy, Primary Dysautonomias, Inflammatory Bowel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vagal nerve stimulation (VNS)Device
Also called Cyberonics VNS
Implantation with vagal nerve stimulator for epilepsy
| Study group | Role | What they receive |
|---|---|---|
| Patients undergoing device implantation | Experimental | Patients undergoing device implantation with vagal nerve stimulator (VNS) for epilepsy Receives: Device: Vagal nerve stimulation (VNS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Metagenomic microbiome profile
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.
Measured: 1 year
Bowel movement frequency
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.
Measured: 1 year
Bowel habits
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.
Measured: 1 year
Immune Profile 1 - Flow cytometric profiling of cell populations
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
Measured: 1 year
Immune Profile 2 - Ex vivo stimulation of cells in whole blood
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.
Measured: 1 year
Inflammatory Profile 1 - Meso Scale Discovery (or MSD) analysis for pro-inflammatory cytokines/chemokines
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
Measured: 1 year
Inflammatory Profile 2 - Meso Scale Discovery (or MSD) analysis for metabolic hormones
Serum electrochemiluminescence detection analysis of the following hormones: GLP-1, insulin, Glucagon, Leptin. All in picograms/mL.
Measured: 1 year
Inflammatory Profile 3 - Metabolomics for Short Chain Fatty acids (SCFAs)
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.
Measured: 1 year
Inflammatory Profile 4 - Intestinal inflammation and permeability markers
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
Measured: 1 year
Secondary outcomes (1)
Epilepsy severity
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. Additionally, 1 year Engel outcome will be assessed.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2019
- Study start1 Apr 2021
- Primary completion13 Dec 2025 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Autoimmune DiseasesStudies of the same condition, open and under way.
- More trials run by University of LouisvilleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Prospective single-arm with internal control group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Louisville
- Sponsor type
- University, hospital or other
- Collaborators
- LivaNova, Norton Healthcare
- Responsible party
- Principal investigator, Ian Mutchnick, University of Louisville
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03953768
- Sponsor's protocol ID
- 19.0330
- Acronym
- VNS-IG
- Status last verified
- Nov 2024
- First submitted
- 15 Apr 2019
- Last updated
- 25 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Non-randomized Single-arm Trial of Efferent Neuromodulation Immune and Gastrointestinal Systems by VNS in the Epilepsy Population
- ClinicalTrials.gov ID
- NCT03953768
- Acronym / sponsor ID
- VNS-IG / 19.0330
- Keywords
- epilepsy, vagal, autoimmune, autonomic, inflammatory bowel disease, immune
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University of LouisvilleUniversity, hospital or other
- Collaborators
- LivaNova, Norton Healthcare
- Study start
- 1 Apr 2021 (actual)
- Primary completion
- 13 Dec 2025 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 17 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Prospective single-arm with internal control group
| Arm | Type | Receives |
|---|---|---|
| Patients undergoing device implantation | Experimental | Device: Vagal nerve stimulation (VNS)Patients undergoing device implantation with vagal nerve stimulator (VNS) for epilepsy |
Who may qualify
- Ages
- 0 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Undergoing VNS implantation for the first time as a treatment for epilepsy and
- 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.
- 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.
Key exclusion criteria (10 listed)
- Previous treatment with VNS (other than the one implanted for this study)
- Current pregnancy (contraindication to surgery)
- Active infection
- History of cancer or treatment with chemotherapy
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vagal nerve stimulation (VNS)Also: Cyberonics VNSImplantation with vagal nerve stimulator for epilepsy | Device | Patients undergoing device implantation |
Primary outcome
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.
Bowel habits
Time frame: 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
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
1 secondary outcome
Epilepsy severity
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Meena A Vessell, MD contact
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Vagal nerve stimulation (VNS) in people with Autoimmune Diseases and Epilepsy, run by University of Louisville at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ian S Mutchnick, MD (5026295512, ianmutchnick@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Metagenomic microbiome profile (time frame: 1 year). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2024.