Clinical Trial: Blinking and Yawning in Epilepsy: The Role of Dopamine

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Dopaminergic Reactivity In Idiopathic Generalized Epilepsy: A "Proof Of Concept" Clinical, Pharmacological And Neurophysiological Study

Brief Summary:

The objective of the present study is to assess dopaminergic reactivity with behavioural markers (i.e. yawning and blinking) in patients with idiopathic generalized epilepsy compared to matched healthy controls, after injection of either low dose of apomorphine or placebo.

Other parameters will be recorded: biochemical (prolactin, GH) and neurophysiological (Spike-Waves Discharge: SWD rating). Safety parameters will be recorded to assess tolerance.

Detailed Summary:

Clinical data regarding the effects of dopaminergic drugs in idiopathic generalized epilepsies are scarce. The general observation that antipsychotic agents (dopaminergic antagonists) worsen seizures, has suggested that dopaminergic agonists would have antiepileptic effects. However, this has never been clearly demonstrated, besides in few limited studies (Mervaala, 1990 ; Quesney, 1980, 1981). More recently, Positron Emission Tomography (PET) investigations using dopaminergic markers (Fluoro-Dopa, SCH23390, DAT) have shown dopaminergic deficits in several epileptic syndromes: ring chromosome 20 syndrome (Biraben 2004), juvenile myoclonic epilepsy (Ciumas 2008), temporal lobe epilepsy (Bouilleret 2008), frontal lobe epilepsy (Fedi 2008). These data give rise to a renewal of interest for the involvement of the dopaminergic neurotransmission in epilepsies. Based on our experimental data from animal studies (see Deransart and Depaulis, 2002), the investigators propose an original study investigating the involvement of the dopaminergic system in idiopathic generalized epilepsies using behavioural as well as neurophysiological markers of the dopaminergic response, in conditions where seizing activities in patients are facilitated (EEG follow-up after sleep deprivation). This approach is based on the concept developed in our laboratory concerning the involvement of the basal ganglia, and more precisely the dopaminergic pathways, in the control of spike-wave discharges in idiopathic generalized epilepsies.

The primary objective is to assess dopaminergic reactivity using a behavioural marker (i.e. yawning) in patients with idiopathic generalized epilepsy compared to matched healthy controls after injection of either low dose of apomorphine or placebo. Other parameters will be recorded as secondary outcomes: behavioural (blinking), biochemical (prolactin, GH) and neurophysiologica
Sponsor: Institut National de la Santé Et de la Recherche Médicale, France

Current Primary Outcome:

• Number of yawn [ Time Frame: 60 minutes after injections ]
  Number of yawn at 60 minuts after the injection of apomorphine in patients with idiopathic generalized epilepsy compared to healthy volunteers.
• Number of eyelid blinking [ Time Frame: 60 minutes after injections ]
  Number of eyelid Blinking at 60 minuts after the injection of apomorphine in patients with idiopathic generalized epilepsy compared to healthy volunteers.

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Number of yawn [ Time Frame: at 60 minutes after injections ]
  Evolution of yawn number between base line period and the 60 minuts following the injection of apomorphine in patients with idiopathic generalized epilepsy compared to healthy volunteers matched.
• Number of eyelid blinking in both groups after apomorphin or placebo injection [ Time Frame: at 60 minutes after injections ]
  The number of eyelid blinking after apomorphin or placebo injection is compare in both groups
• Neurophysiological assessment of the dopaminergic reactivity [ Time Frame: 60 min ]
  Number and cumulated duration of Spike-waves discharge assessed after injection of apomorphine in patients with idiopathic generalized epilepsy
• To test the correlation between the behavioral and neurophysiological markers of dopaminergic reactivity in patients with epilepsy [ Time Frame: 60 min ]
  Correlation between yawning/blinking and the number of Spike-wave discharges in patients with epilepsy (Pearson test)
• To assess dopaminergic reactivity with biological markers [ Time Frame: 60 min ]
  Comparison between plasma concentrations of prolactin and growth hormone (GH) in patients and controls after injection of apomorphine or placebo.
• Number of Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 4 weeks ]
  This is a descriptive outcome. The number of each adverse event occured at 4 weeks will be listed
• Check the absence of spike-wave discharges in healthy volunteers [ Time Frame: 60 min ]
  EEG analysis

Original Secondary Outcome: Same as current

Information By: Institut National de la Santé Et de la Recherche Médicale, France

Dates:
Date Received: June 14, 2011
Date Started: September 2011
Date Completion:
Last Updated: November 4, 2016
Last Verified: November 2016