PET Study of the Nicotinic System in Epilepsy
NICOPET
1 other identifier
interventional
48
0 countries
N/A
Brief Summary
Mutations in neuronal nicotinic acetylcholine receptors (nAChRs) have been identified in the autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). Despite the demonstration of a gain of function of the mutated receptors, the precise mechanisms leading to this nocturnal epilepsy are still unknown. In 2006 the investigators studied the nAChR cerebral distribution in a group of patients with ADNFLE carrying a nAChR mutation, by a PET-scan using \[18F\]-F-A-85380, a ligand with a high affinity and specificity for alpha4beta2 nicotinic receptors. The study showed a different pattern of brain distribution of the radiotracer in the ADNFLE patients when compared to a group of control subjects, with a significant increase of nicotinic receptor density in the patients in mesencephalon and cerebellum (Picard et al., Brain 2006). Based on the known biochemical and cellular circuits in the brainstem, these results suggest that the nAChR density increase in mesencephalon is involved in the pathophysiology of ADNFLE through the role of brainstem ascending cholinergic systems in arousal. The follow-up step consists of extending this examination to other forms of epilepsy, in order to verify the specificity of the hyperfixation pattern for ADNFLE, and search for a potential involvement of nicotinic receptors in other forms of epilepsy. The investigators aim to study 5 groups of subjects: control subjects (Group 1, 20 subjects); patients with a non lesional partial epilepsy and a predominance of diurnal seizures (Group 2, 12 subjects); patients with an idiopathic generalized epilepsy (Group 3, 12 subjects); patients with nocturnal frontal lobe epilepsy (Group 4, 3 subjects) and epileptic patients with vagal nerve stimulation (Group 5, 1 subject). For each patient, a cerebral MRI, \[18F\]- fluorodeoxyglucose (FDG) PET/CT and \[18F\]-F-A-85380 PET/CT examinations are planned. The investigators will perform data analyses on volume of distribution (Vt) parametric images which will be based on the ratio of brain tissue to unchanged F-A-85380 plasma at equilibrium. Statistical parametric mapping (SPM2) will be used to further study the parametric PET images. This study is primarily dedicated to demonstrate that the pattern of hyperfixation that was obtained in ADNFLE patients is specific for this disorder and does not constitute a common pattern to various forms of epilepsy. The investigators will also search for a possible involvement of the nAChRs in other forms of epilepsy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for not_applicable
Started Feb 2012
Longer than P75 for not_applicable
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 1, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2015
CompletedFirst Submitted
Initial submission to the registry
August 24, 2017
CompletedFirst Posted
Study publicly available on registry
August 31, 2017
CompletedAugust 31, 2017
August 1, 2017
3.8 years
August 24, 2017
August 30, 2017
Conditions
Outcome Measures
Primary Outcomes (1)
Comparison of the cerebral distribution of the neuronal nicotinic acetylcholine receptors (nAChR) in the 5 groups of individuals by means of voxelwise and regional 18F-FA binding potential measurements
Parametric 18F-FA and 18F-FDG binding potential measurements will be compared between the different groups of patients with epilepsy and the control group in order to find specific changes in the cerebral distribution of the nicotinic receptors in the different types of epilepsy, by using a voxel-wise (SPM) and a volume of interest (VOI) analysis.
1 month
Study Arms (5)
Control group
ACTIVE COMPARATORNon lesional diurnal partial epilepsy
EXPERIMENTALIdiopathic generalized epilepsy
EXPERIMENTALNocturnal frontal lobe epilepsy
EXPERIMENTALEpileptic patients with Vagus Nerve Stimulation (VNS)
EXPERIMENTALInterventions
to eliminate a structural intra-cerebral lesion
exam performed after iv injection of 200 MBq \[18F\]F-A-85380
exam performed after iv injection of 200 MBq \[18F\]FDG
Eligibility Criteria
You may qualify if:
- males
- years old
- non-smokers
You may not qualify if:
- smoking during the past twelve months
- contraindications to MRI
- brain lesions on MRI (including hippocampal atrophy)
- neurological disorder (other than epilepsy) or psychiatric disorder
- neoplasia or coronary disease
- blood test showing : creatinine clearance \< 50 ml/min, or platelet \< 100 G/l, or leucocytes \< 3.8 G/l, or ALT or AST \> 2 x upper standard, or gamma-GT \> 3 x upper standard, or albumin \< 35 g/l or \> 48 g/l .
- patients only : nuclear imaging during the past twelve months
- healthy volunteers only : ionising radiation exam during the past five years
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Fabienne PICARDlead
Related Publications (1)
Picard F, Bruel D, Servent D, Saba W, Fruchart-Gaillard C, Schollhorn-Peyronneau MA, Roumenov D, Brodtkorb E, Zuberi S, Gambardella A, Steinborn B, Hufnagel A, Valette H, Bottlaender M. Alteration of the in vivo nicotinic receptor density in ADNFLE patients: a PET study. Brain. 2006 Aug;129(Pt 8):2047-60. doi: 10.1093/brain/awl156. Epub 2006 Jun 30.
PMID: 16815873BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- BASIC SCIENCE
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Doctor, University Hospital, Geneva
Study Record Dates
First Submitted
August 24, 2017
First Posted
August 31, 2017
Study Start
February 1, 2012
Primary Completion
November 1, 2015
Study Completion
November 1, 2015
Last Updated
August 31, 2017
Record last verified: 2017-08