1) To study the effect of VNS on the aberrant set point of the monocyte-macrophage-dendritic cell system in patients with refractory epilepsy 2) To investigate whether a correction of this setpoint induces anticonvulsive and neuroprotective effects…
ID
Source
Brief title
Condition
- Seizures (incl subtypes)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
> 50% seizure reduction
Secondary outcome
Demographic data and epilepsy specific data:
- age
- gender
- seizure and epilepsy syndrome classification
- duration of epilepsy
- seizure frequency (diary)
- seizure severity
Neuro-immunologic variables (pro-, and anti-inflammatory cytokines and
neuroprotective cytokines)
Biochemical variables (serotonin metabolites, GABA, glutamate)
Endocrine variables (cortisol)
Neuropsychologic variables (mood and quality of life)
Background summary
Repetitive seizures increase pro*inflammatory cytokines in the peripheral
blood. Experimentally it has been shown that activation of inflammatory
cytokines by peripheral administration of a toxic agens causes sickness
behaviour. Pro-inflammatory cytokines interfere with the catabolisation of a
precursor of Serotonin (Tryptophan). Tryptophan is catabolised to an endogen
NMDA receptor agonist. NMDA (an excitatory neurotransmitter) produce neuronal
damage.
The Vagus Nerve (VN) plays an important role in the interaction between the
immune and neurotransmitter system in which cytokines are crucial. Vagus nerve
stimulation (VNS) is associated with marked peripheral increases in pro-, and
anti-inflammatory cytokines. VNS has also an effect on various amino-acid pools
in the brain. Given the complexity of the immune system and its interaction
with neurotransmitter and endocrine systems in the human brain it is not
surprising to find that pro-,and anti-inflammatory immune factors play a role
in the etiology and the course of affective disorders. It is to be expected
that immune modulation also plays a role in the course of epilepsy.
Study objective
1) To study the effect of VNS on the aberrant set point of the
monocyte-macrophage-dendritic cell system in patients with refractory epilepsy
2) To investigate whether a correction of this setpoint induces anticonvulsive
and neuroprotective effects
Study design
Study design: Prospective observational longitudinal cohort.
The VNS device is implanted after a baseline period of three month. Two weeks
after surgery activation of the device will take place.
At the baseline, two weeks after surgery and after six month of actual
treatment neurocognitive screening and blood analysis will take place. During
the total study period the patients will list their seizures using a seizure
diary.
Study burden and risks
Patients who participate in the VN Mood study will have four extra
bloodsamplings and two neuropsychologic screening sessions. On two occasions
bloodsampling will include a dexamethason test (1 mg dexamethason taken on the
evening prior to bloodsampling). There are no risk factors other than the risk
factors seen in usual VNS treatment. The benefit for the individual patient:
the extra information on mood, and quality of life as well as the information
on several biochemical and pharmacologic parameters may be of help in guiding
the patient.
Postbus 5800
6202AZ Maastricht
Nederland
Postbus 5800
6202AZ Maastricht
Nederland
Listed location countries
Age
Inclusion criteria
1) Patients treated with Vagus Nerve stimulation as part of usual patient care
2) Age 18 years or older
3) Informed consent
Exclusion criteria
1) Evidence of a progressive cerebral lesion, degenerative disorder, malignancy or a history with malignancy in the past 5 years
2) Unstable medical disease (i.e. cardiovascular, hepatic, renal, gynaecologic, musculoskeletal, gastrointestinal, metabolic, endocrine) in the last 2 years
3) Documented history with generalized status epilepticus in the past three months
4) High risks for complications (obstructive respiratory disease, gastric disorders, cardiac rythm disorders)
5) A history of alcohol or drug abuse, of psychiatric disorder requiring electro-convulsive therapy, chronic use of major tranquillisers (neuroleptics, antidepressants, or MAO inhibitors) in the past 6 months
6) Regularly treatment with antihistamines, metoclopramide or CNS-active compounds
7) Treatment with an experimental drug during the past 30 days
8) Subjects who are schizophrenic or have exhibited any psychotic symptomatology
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 | NL13166.068.06 |