Blinking and Yawning in Epilepsy: The Role of Dopamine

NCT01432821 | Completed

• 1 other identifier: C10-27
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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.

Conditions

Idiopathic Generalized Epilepsy

Keywords

Epilepsy,; dopamine; yawning,; blinking eyelids,; electroencephalography

Outcome Measures

Primary Outcomes (2)

• Number of yawn

  Number of yawn at 60 minuts after the injection of apomorphine in patients with idiopathic generalized epilepsy compared to healthy volunteers.

  60 minutes after injections

• Number of eyelid blinking

  Number of eyelid Blinking at 60 minuts after the injection of apomorphine in patients with idiopathic generalized epilepsy compared to healthy volunteers.

  60 minutes after injections

Secondary Outcomes (7)

• Number of yawn

  at 60 minutes after injections

• Number of eyelid blinking in both groups after apomorphin or placebo injection

  at 60 minutes after injections

• Neurophysiological assessment of the dopaminergic reactivity

  60 min

• To test the correlation between the behavioral and neurophysiological markers of dopaminergic reactivity in patients with epilepsy

  60 min

• To assess dopaminergic reactivity with biological markers

  60 min

Study Arms (2)

Apomorphine

EXPERIMENTAL

After randomization healthy volunteers or patients with idiopathic generalized epilepsy receive: -sequence A: 1 mg/kg and then 5 mg/kg of apomorphine

Other: Apomorphine (Experimental product)

Saline

PLACEBO COMPARATOR

After randomization healthy volunteers or patients with idiopathic generalized epilepsy receive: sequence B: 2 injections of saline

Other: Apomorphine (Experimental product)

Interventions

Apomorphine (Experimental product) OTHER

Dosage Form: Injection Dosage: 1 or 5 mg / kg Route of administration: Subcutaneous Duration of treatment: two injections of apomorphine followed by two injections of a placebo one week after or vice versa. Two injections will be made by visiting during visits 2 and 3. The study was conducted cross-over with two visits EEG recording, the order will be randomized injections: * Sequence A during visit 2 followed by sequence B during visit 3 * or sequence B during visit 2

Apomorphine; Saline

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• For patients:
• Men and women aged between 18 and 40
• Person affiliated to social security or beneficiary of such a regime
• idiopathic generalized epilepsy treated with lamotrigine, an association of lamotrigine, topiramate, levetiracetam, lamotrigine or levetiracetam alone (group patients) for at least 14 days without changing doses The idiopathic generalized epilepsy is defined by generalized seizures: generalized tonic-clonic seizures, absences or myoclonic seizures, excluding any other type of seizure, and electroencephalographic appearance following: presence of interictal EEG discharge generalized to type of spikes, spike-wave or wave polyspikes generalized, sporadic or rhythmic\> or = 3 Hz background activity is normal.
• For healthy volunteers:
• Men and women aged between 18 and 40
• Person affiliated to social security or beneficiary of such a regime

You may not qualify if:

• Topic wrongly included
• Deflecting protocol that can skew the primary endpoint
• Primary endpoint missing
• If the investigator considers the health of the subject is incompatible with the continuation of the study.
• For patients:
• The presence of interictal focal discharges on EEG previous
• The emergence of partial seizures
• Restless Leg Syndrome
• All non-antiepileptic treatment may affect levels of dopamine
• Current use of illicit drugs.
• A person deprived of liberty by judicial or administrative person being a measure of legal protection.
• Pregnant, parturient, lactating mother.
• For women, lack of effective contraception
• For healthy volunteers:
• Any medical treatment associated

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead

Study Sites (1)

CIC Department - University Hospital of Grenoble

La Tronche, Isere, 38700, France

Location

Related Publications (5)

• Ahmad S, Fowler LJ, Whitton PS. Effect of acute and chronic lamotrigine on basal and stimulated extracellular 5-hydroxytryptamine and dopamine in the hippocampus of the freely moving rat. Br J Pharmacol. 2004 May;142(1):136-42. doi: 10.1038/sj.bjp.0705737. Epub 2004 Mar 22.

  PMID: 15037514 BACKGROUND

• Ahmad S, Fowler LJ, Whitton PS. Lamotrigine, carbamazepine and phenytoin differentially alter extracellular levels of 5-hydroxytryptamine, dopamine and amino acids. Epilepsy Res. 2005 Feb;63(2-3):141-9. doi: 10.1016/j.eplepsyres.2005.02.002.

  PMID: 15777732 BACKGROUND

• Aymard G, Berlin I, de Brettes B, Diquet B. Pharmacokinetic-pharmacodynamic study of apomorphine's effect on growth hormone secretion in healthy subjects. Fundam Clin Pharmacol. 2003 Aug;17(4):473-81. doi: 10.1046/j.1472-8206.2003.00152.x.

  PMID: 12914551 BACKGROUND

• Biraben A, Semah F, Ribeiro MJ, Douaud G, Remy P, Depaulis A. PET evidence for a role of the basal ganglia in patients with ring chromosome 20 epilepsy. Neurology. 2004 Jul 13;63(1):73-7. doi: 10.1212/01.wnl.0000132840.40838.13.

  PMID: 15249613 BACKGROUND

• Blin O, Masson G, Azulay JP, Fondarai J, Serratrice G. Apomorphine-induced blinking and yawning in healthy volunteers. Br J Clin Pharmacol. 1990 Nov;30(5):769-73. doi: 10.1111/j.1365-2125.1990.tb03848.x.

  PMID: 2271377 BACKGROUND

MeSH Terms

Conditions

Epilepsy, Idiopathic Generalized; Epilepsy

Interventions

Apomorphine

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Aporphines; Benzylisoquinolines; Alkaloids; Heterocyclic Compounds; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 4 or More Rings

Study Officials

• Laurent VERCUEIL, Doctor

  Institut National de la Santé Et de la Recherche Médicale, France

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2011
• First Posted: September 13, 2011
• Study Start: September 1, 2011
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2014
• Last Updated: February 18, 2026

Record last verified: 2016-11

Locations

FR (1)