Acute and Long Term Effects of VNS on Memory in Patients With Refractory Epilepsy

Study Overview
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Brief Summary
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Refractory epilepsy patients implanted with a vagus nerve stimulator perform a memory test at baseline in three conditions: invasive vagus nerve stimulation (VNS), transcutaneous vagus nerve stimulation (taVNS) and sham stimulation. After 6 weeks of VNS treatment, the memory test is repeated in two condition: invasive vagus nerve stimulation (VNS) and sham stimulation. The endpoint of this experiment is assessing the effect of VNS and taVNS on memory performance.

Detailed Description
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Previous studies underlined the potential of both invasive as transcutaneous auricular vagus nerve stimulation to ameliorate certain cognitive functions. In this randomized, controlled cross-over within-subjects study, a memory test is conducted in patients with refractory epilepsy who are implanted with a vagus nerve stimulation. The memory test consists out of a word recognition paradigm based on the study of Clarck et al. published in 1999 in Nature Neuroscience. Testing is performed at baseline (before start of the stimulation) and after 6 weeks of treatment with vagus nerve stimulation. During the first session, the patients complete the word recognition task during three interventions: Invasive vagus nerve stimulation Transcutaneous vagus nerve stimulation (cymba concha) Sham vagus nerve stimulation (no stimulation) During the second session, the patients complete the word recognition task during two interventions: Invasive vagus nerve stimulation Sham vagus nerve stimulation (no stimulation) The goal is to investigate if invasive vagus nerve stimulation and transcutaneous nerve stimulation can influence (i.e. improve) the performance on the memory task and if this performance is improved after 6 weeks of VNS treatment.

Official Title
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Research on the Acute and Long Term Effects on Memory and the Mechanism of Action of Vagus Nerve Stimulation in Patients With Refractory Epilepsy

Conditions
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Refractory Epilepsy

Intervention / Treatment
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* Diagnostic Test: Memory task


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Refractory epilepsy Treated with vagus nerve stimulation IQ >= 70 and able to perform the memory task Exclusion Criteria: IQ < 70

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vagus nerve stimulation<br>Invasive vagus nerve stimulation | Diagnostic Test: Memory task<br>* Word recognition task<br>|
| Experimental: Transcutaneous vagus nerve stimulation<br>Cymba concha stimulation | Diagnostic Test: Memory task<br>* Word recognition task<br>|
| Sham Comparator: Sham vagus nerve stimulation<br>No vagus nerve stimulation | Diagnostic Test: Memory task<br>* Word recognition task<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immediate recall score at session 1 | Free recall score for correctly recalled words (min score 0,max score 21, higher score indicates better performance), calculated as a percentage | At baseline | 
| Immediate recall score at session 2 | Free recall score for correctly recalled words (min score 0, max score 21, higher score indicates better performance)), calculated as a percentage | After 6 weeks of VNS treatment | 
| Delayed recognition scores at session 1 | Hitscore for correctly recognized target words (min score 0,max score 63, higher score indicates better performance), score for not recognized target words= misses (min score 0,max score 63, higher score indicates worse performance),correct rejection score of non-target related words (min score 0,max score 63, higher score indicates better performance), score for incorrect recognition of non-target related words= false alarms (min score 0,max score 63, higher score indicates worse performance), discrimination index= hit score -false alarm score (min score 0,max score 63, higher score indicates better performance). All scores are calculated as a percentage. | At baseline | 
| Delayed recognition scores at session 2 | Hitscore for correctly recognized target words (min score 0,max score 48, higher score indicates better performance), score for not recognized target words= misses (min score 0,max score 48, higher score indicates worse performance),correct rejection score of non-target related words (min score 0,max score 48, higher score indicates better performance), score for incorrect recognition of non-target related words= false alarms (min score 0,max score 48, higher score indicates worse performance), discrimination index= hit score -false alarm score (min score 0,max score 48, higher score indicates better performance). All scores are calculated as a percentage. | After 6 weeks of VNS treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Attention score at session 1 | Score of correct responses on 6 open question (min score 0, max score 6, higher score indicates better performance), calculated as a percentage | At baseline | 
| Attention score at session 2 | Score of correct responses on 6 open question (min score 0, max score 6, higher score indicates better performance), calculated as a percentage | After 6 weeks of VNS treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vagus nerve stimulation, Transcutaneous vagus nerve stimulation, Word recognition paradigm