<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03268369</url>
  </required_header>
  <id_info>
    <org_study_id>10-041</org_study_id>
    <nct_id>NCT03268369</nct_id>
  </id_info>
  <brief_title>PET Study of the Nicotinic System in Epilepsy</brief_title>
  <acronym>NICOPET</acronym>
  <official_title>PET Study of the Nicotinic System in Epilepsy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fabienne PICARD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Geneva</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Mutations in neuronal nicotinic acetylcholine receptors (nAChRs) have been identified in the&#xD;
      autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). Despite the demonstration of a&#xD;
      gain of function of the mutated receptors, the precise mechanisms leading to this nocturnal&#xD;
      epilepsy are still unknown. In 2006 the investigators studied the nAChR cerebral distribution&#xD;
      in a group of patients with ADNFLE carrying a nAChR mutation, by a PET-scan using&#xD;
      [18F]-F-A-85380, a ligand with a high affinity and specificity for alpha4beta2 nicotinic&#xD;
      receptors. The study showed a different pattern of brain distribution of the radiotracer in&#xD;
      the ADNFLE patients when compared to a group of control subjects, with a significant increase&#xD;
      of nicotinic receptor density in the patients in mesencephalon and cerebellum (Picard et al.,&#xD;
      Brain 2006). Based on the known biochemical and cellular circuits in the brainstem, these&#xD;
      results suggest that the nAChR density increase in mesencephalon is involved in the&#xD;
      pathophysiology of ADNFLE through the role of brainstem ascending cholinergic systems in&#xD;
      arousal. The follow-up step consists of extending this examination to other forms of&#xD;
      epilepsy, in order to verify the specificity of the hyperfixation pattern for ADNFLE, and&#xD;
      search for a potential involvement of nicotinic receptors in other forms of epilepsy. The&#xD;
      investigators aim to study 5 groups of subjects: control subjects (Group 1, 20 subjects);&#xD;
      patients with a non lesional partial epilepsy and a predominance of diurnal seizures (Group&#xD;
      2, 12 subjects); patients with an idiopathic generalized epilepsy (Group 3, 12 subjects);&#xD;
      patients with nocturnal frontal lobe epilepsy (Group 4, 3 subjects) and epileptic patients&#xD;
      with vagal nerve stimulation (Group 5, 1 subject). For each patient, a cerebral MRI, [18F]-&#xD;
      fluorodeoxyglucose (FDG) PET/CT and [18F]-F-A-85380 PET/CT examinations are planned. The&#xD;
      investigators will perform data analyses on volume of distribution (Vt) parametric images&#xD;
      which will be based on the ratio of brain tissue to unchanged F-A-85380 plasma at&#xD;
      equilibrium. Statistical parametric mapping (SPM2) will be used to further study the&#xD;
      parametric PET images. This study is primarily dedicated to demonstrate that the pattern of&#xD;
      hyperfixation that was obtained in ADNFLE patients is specific for this disorder and does not&#xD;
      constitute a common pattern to various forms of epilepsy. The investigators will also search&#xD;
      for a possible involvement of the nAChRs in other forms of epilepsy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 2012</start_date>
  <completion_date type="Actual">November 2015</completion_date>
  <primary_completion_date type="Actual">November 2015</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>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</measure>
    <time_frame>1 month</time_frame>
    <description>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.</description>
  </primary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">48</enrollment>
  <condition>Epilepsy</condition>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Non lesional diurnal partial epilepsy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Idiopathic generalized epilepsy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Nocturnal frontal lobe epilepsy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Epileptic patients with Vagus Nerve Stimulation (VNS)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>MRI of the brain</intervention_name>
    <description>to eliminate a structural intra-cerebral lesion</description>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_label>Idiopathic generalized epilepsy</arm_group_label>
    <arm_group_label>Nocturnal frontal lobe epilepsy</arm_group_label>
    <arm_group_label>Non lesional diurnal partial epilepsy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>PET scan [18F]F-A-85380</intervention_name>
    <description>exam performed after iv injection of 200 MBq [18F]F-A-85380</description>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_label>Epileptic patients with Vagus Nerve Stimulation (VNS)</arm_group_label>
    <arm_group_label>Idiopathic generalized epilepsy</arm_group_label>
    <arm_group_label>Nocturnal frontal lobe epilepsy</arm_group_label>
    <arm_group_label>Non lesional diurnal partial epilepsy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>PET scan [18F]FDG</intervention_name>
    <description>exam performed after iv injection of 200 MBq [18F]FDG</description>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_label>Epileptic patients with Vagus Nerve Stimulation (VNS)</arm_group_label>
    <arm_group_label>Idiopathic generalized epilepsy</arm_group_label>
    <arm_group_label>Nocturnal frontal lobe epilepsy</arm_group_label>
    <arm_group_label>Non lesional diurnal partial epilepsy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  males&#xD;
&#xD;
          -  18-60 years old&#xD;
&#xD;
          -  non-smokers&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  smoking during the past twelve months&#xD;
&#xD;
          -  contraindications to MRI&#xD;
&#xD;
          -  brain lesions on MRI (including hippocampal atrophy)&#xD;
&#xD;
          -  neurological disorder (other than epilepsy) or psychiatric disorder&#xD;
&#xD;
          -  neoplasia or coronary disease&#xD;
&#xD;
          -  blood test showing : creatinine clearance &lt; 50 ml/min, or platelet &lt; 100 G/l, or&#xD;
             leucocytes &lt; 3.8 G/l, or ALT or AST &gt; 2 x upper standard, or gamma-GT &gt; 3 x upper&#xD;
             standard, or albumin &lt; 35 g/l or &gt; 48 g/l .&#xD;
&#xD;
          -  patients only : nuclear imaging during the past twelve months&#xD;
&#xD;
          -  healthy volunteers only : ionising radiation exam during the past five years&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <reference>
    <citation>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.</citation>
    <PMID>16815873</PMID>
  </reference>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 24, 2017</study_first_submitted>
  <study_first_submitted_qc>August 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 31, 2017</study_first_posted>
  <last_update_submitted>August 30, 2017</last_update_submitted>
  <last_update_submitted_qc>August 30, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 31, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University Hospital, Geneva</investigator_affiliation>
    <investigator_full_name>Fabienne PICARD</investigator_full_name>
    <investigator_title>Doctor, University Hospital, Geneva</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Epilepsy</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03268369
org study id: 10-041
nct id: NCT03268369
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: 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
time frame: 1 month
description: 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.
arm group label: Control group
arm group type: Active Comparator
arm group label: Non lesional diurnal partial epilepsy
arm group type: Experimental
arm group label: Idiopathic generalized epilepsy
arm group type: Experimental
arm group label: Nocturnal frontal lobe epilepsy
arm group type: Experimental
arm group label: Epileptic patients with Vagus Nerve Stimulation (VNS)
arm group type: Experimental
intervention type: Radiation
intervention name: MRI of the brain
description: to eliminate a structural intra-cerebral lesion
arm group label: Control group
arm group label: Idiopathic generalized epilepsy
arm group label: Nocturnal frontal lobe epilepsy
arm group label: Non lesional diurnal partial epilepsy
intervention type: Radiation
intervention name: PET scan [18F]F-A-85380
description: exam performed after iv injection of 200 MBq [18F]F-A-85380
arm group label: Control group
arm group label: Epileptic patients with Vagus Nerve Stimulation (VNS)
arm group label: Idiopathic generalized epilepsy
arm group label: Nocturnal frontal lobe epilepsy
arm group label: Non lesional diurnal partial epilepsy
intervention type: Radiation
intervention name: PET scan [18F]FDG
description: exam performed after iv injection of 200 MBq [18F]FDG
arm group label: Control group
arm group label: Epileptic patients with Vagus Nerve Stimulation (VNS)
arm group label: Idiopathic generalized epilepsy
arm group label: Nocturnal frontal lobe epilepsy
arm group label: Non lesional diurnal partial epilepsy
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
citation: 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: 16815873
responsible party type: Sponsor-Investigator
investigator affiliation: University Hospital, Geneva
investigator full name: Fabienne PICARD
investigator title: Doctor, University Hospital, Geneva
mesh term: Epilepsy