Therefore, this study aims to improve the understanding of the physiological effect of VNS on intestinal permeability, intestinal microbiota, immunological parameters in blood and breath in drug resistant epilepsy (DRE) patients. Additionally, this…
ID
Source
Brief title
Condition
- Seizures (incl subtypes)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Intestinal permeability (LPS binding protein, main study parameter)
Secondary outcome
Intestinal microbiome, intestinal inflammation (calprotectin), immunological
parameters (general immunological function (IL-1-beta, IL-6, IL-8, IL-10,
IFN-gamma, TNF-alpha, IL-1RA, CRP); blood-brain-barrier (GFAP, S100b);
neurotrophins (neurotrophin-3, BDNF, neurofilament H, neurofilament L); and
metabolic factors (IGF-1, IGF-1R, leptin, insulin)), volatile organic compounds
(VOC) before and after implantation
Background summary
Based on the evidence regarding intestinal permeability and microbiome
disturbances in patients with epilepsy and in mood disorders, combined with the
restoring effects of vagus nerve stimulation (VNS) on intestinal mucosa in
animal models and patients with inflammatory bowel disease, we hypothesize that
VNS also has an indirect effect on quality-of-life/depressive symptoms/seizure
frequency via improvement of microbiota balance, intestinal permeability and an
associated decrease in immunological dysregulation in patients with drug
resistant epilepsy (DRE).
Furthermore, we hypothesize that in DRE-cases with increased intestinal
permeability, intestinal microbiota disbalance and/or immunological aberrations
at baseline, VNS will have a stronger ameliorating effect on
quality-of-life/depressive symptoms/seizure frequency. These biomarkers may
therefore be suitable as potential treatment response predictor candidates.
Study objective
Therefore, this study aims to improve the understanding of the physiological
effect of VNS on intestinal permeability, intestinal microbiota, immunological
parameters in blood and breath in drug resistant epilepsy (DRE) patients.
Additionally, this study aims to predict improvement of quality of life,
reduction of depressive symptomatology and seizure frequency one year after VNS
implantation, based on these measurements at baseline.
Study design
Observational before and after design.
Measurements will be made before and up to 1 year after clinical VNS
implantation. Blood samples, fecal samples, breath samples, epilepsy
characteristics and psychometrics (including depression symptomatology), will
be taken at baseline, before VNS implantation. These measurements will be
repeated 1 year post implantation. Quality of life, depression symptomatology,
and epilepsy characteristics will be measured every 3 months in between as
well.
Study burden and risks
The number of patient visits will be limited and mainly requires time
investment for few physical examinations and questionnaires. Stool samples are
collected twice in a developed way that is generally well accepted. Blood
samples and breath samples will be collected at two occasions by experienced
researchers or lab technicians, so health risk attributable to this procedure
is minimal as well.
Potential benefits of participation concern that routine care consists of less
extensive monitoring of symptom change and functioning compared to the current
trial, so all patients may benefit from the thorough examinations during study
participation.
In the face of the limited additional burden for the patient when participating
in the current trial as compared to routine treatment, and the possible
positive outcome for future treatment, offering participation to selected
patients appears to be justified.
Hanzeplein 1
Groningen 9700RB
NL
Hanzeplein 1
Groningen 9700RB
NL
Listed location countries
Age
Inclusion criteria
- Drug-resistent epilepsy (DRE) patients that are accepted for VNS therapy
- Adult (18 years or older) and is capable of providing informed consent
Exclusion criteria
- Pregnancy or breastfeeding (assessed through anamnesis)
- Mental retardation (IQ score <60)
- Any clinically significant or unstable medical disorder as determined by the
investigators, including inflammatory bowel disease, short-bowel syndrome or
acute/chronic pancreatitis
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL82125.042.22 |