Refractory Epilepsy in Children Clinical Trial
Official title:
Does VNS Interact With the Serotonergic and Immune System in Children With Intractable Epilepsy? A Randomized Clinical Study.
Clinical randomized controlled observer blinded add-on design. Additionally there will be a
non-controlled follow-up phase of the study. Children (Age 4-18 years) with intractable
epilepsy, and not eligible for resective surgery will be treated with VNS.
Aim of the study:
1. To evaluate tolerability and effectiveness of VNS in children with intractable epilepsy
and cognitive and behavioural problems in a controlled study.
2. To evaluate the effect of VNS on the immune system which, in its turn, will lead to
changes in the serotonin metabolic pathway
3. To link the therapeutic effect of VNS to changes in the serotonin (5HT) metabolic
pathway.
In addition the investigators hope to detect some markers of immune and neurotransmitter
function that enable us to predict 1) Neuronal cell loss in relation to cognitive decline 2)
the response to therapeutic treatment of VNS.
Hypothesis:
The investigators aim to explore neuronal correlates for cognitive morbidity in children
with intractable epilepsy and to relate this to morphologic changes, biochemical markers,
and to epilepsy characteristics.
Correction of the "stressed" pro-inflammatory status of monocytes/macrophages via an
electrical stimulation of the vagus nerve will prevent/ameliorate seizures as well as
behavioural mood symptoms in children with refractory epilepsy, characterized by the
"pro-inflammatory monocyte signature"
| Status | Active, not recruiting |
| Enrollment | 45 |
| Est. completion date | March 2013 |
| Est. primary completion date | March 2012 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 4 Years to 18 Years |
| Eligibility |
Inclusion Criteria: - Seizures not adequately controlled by anti-epileptic drugs of first or second choice with adequate and stable serum anticonvulsant concentrations - Acceptable seizure regulation but intolerable side effects with adequate and stable serum anticonvulsant concentrations - Not eligible for epilepsy surgery - Age between 4 and 18 years - Informed consent Exclusion Criteria: - Evidence of a progressive cerebral lesion, degenerative disorder, malignancy or a history with malignancy in the past 5 years - Unstable medical disease (i.e. cardiovascular, hepatic, renal, musculoskeletal, gastrointestinal, metabolic, endocrine) in the last 2 years - Documented history with generalized status epilepticus in the past three months - High risks for complications (obstructive respiratory disease, gastric disorders, cardiac I disorders) - A history of alcohol or drug abuse, of psychiatric disorder requiring electroconvulsive therapy, chronic use of major tranquillisers (neuroleptics, antidepressants, or MAO inhibitors) in the past 6 months - Regularly treatment with antihistamines, metoclopramide or CNS-active compounds - Treatment with an experimental drug during the past 30 days - Subjects who are schizophrenic or have exhibited any psychotic symptomatology |
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Netherlands | Epilepsiecentrum Kempenhaeghe | Heeze | Noord-Brabant |
| Netherlands | Maastricht University Medical Center | Maastricht | Limburg |
| Lead Sponsor | Collaborator |
|---|---|
| Epilepsiecentrum Kempenhaeghe | Maastricht University Medical Center |
Netherlands,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | seizure frequency reduction of 50% or more | Seizure frequency is measured by using seizure diaries | after 3 and 6 months | No |