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Serotonin Receptors in Seizure Disorders

Primary Purpose

Partial Epilepsy

Status
Completed
Phase
Locations
United States
Study Type
Observational
Intervention
Sponsored by
National Institute of Neurological Disorders and Stroke (NINDS)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an observational trial for Partial Epilepsy focused on measuring Epilepsy, Temporal Lobe, Blood Flow, Metabolism, Localization

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

INCLUSION CRITERIA: Patients must have clinically documented partial seizures with consistent EEG evidence as defined by the 1981 International Classification of Epileptic Seizures, refractory to standard antiepileptic treatment for at least one year. Patients will be in age ranges of 18 to 60. Patients may be male or female. Female patients of child bearing potential will have a pregnancy test prior to each PET scan to ensure that pregnant patients will not participate in the study. During the study, woman of child bearing potential must use a reliable method of birth control. Three groups of patients will be scanned: 50 patients with EEG and clinical evidence for mesial temporal onset with either MRI findings of mesial temporal sclerosis (MTS) or dysplasia or normal MRI studies. 25 patients with apparent neocortical seizure foci. In addition, patients will be screened for the presence of depression in addition to epilepsy; at least 15 patients from groups 1 and 2 who currently meet DSM-IV criteria for the category "Mood disorder due to epilepsy" (293.83), and the subtype "with major Depressive-Like Episode" 296.2 Major Depressive Disorder, Single Episode, or 296.3 Major Depressive Disorder, Recurrent, indicating that subjects meet diagnostic criteria for a major depressive episode. DSM diagnoses will be based on the Research Version of the Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID-I) including the detailed assessment of the course of both epilepsy and depressive symptoms as well as the family history of medical and psychiatric conditions. Twenty healthy normal adults will be included. Controls will be screened in the NINDS Clinical Epilepsy Section outpatient clinic, with physical examination, CBC urinalysis and blood chemistries. Controls with chronic illnesses, taking any medications, or who smoke will be excluded. They will be asked to abstain from alcohol for one week before the study. EXCLUSION CRITERIA: Patients younger than 18 or older than 60 years old will be excluded from the study. Patients with a known treatable seizure etiology such as neoplastic or infectious disease will be excluded. Patients with MRI findings consistent with brain tumors, trauma or AVMs will be excluded. Patients with progressive neurologic disorders. Patients with a history of significant medical disorders, or requiring chronic treatment with other drugs which can not be stopped, except for SSRIs. Patients with cancer. Patients not capable of giving an informed consent. Patients who had seizure activity 24 hours prior to the study.

Sites / Locations

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 3, 1999
Last Updated
June 30, 2017
Sponsor
National Institute of Neurological Disorders and Stroke (NINDS)
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1. Study Identification

Unique Protocol Identification Number
NCT00001932
Brief Title
Serotonin Receptors in Seizure Disorders
Official Title
PET Imaging of Serotonin Receptors in Seizure Disorders
Study Type
Observational

2. Study Status

Record Verification Date
August 15, 2007
Overall Recruitment Status
Completed
Study Start Date
June 21, 1999 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
August 15, 2007 (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
National Institute of Neurological Disorders and Stroke (NINDS)

4. Oversight

5. Study Description

Brief Summary
Patients in this study will undergo PET scans (a type of nuclear imaging test) to look for abnormalities in certain brain proteins associated with seizures. Studies in animals have shown that serotonin-a chemical messenger produced by the body-attaches to proteins on brain cells called 5HT1A receptors and changes them in some way that may help control seizures. There is little information on these changes, however. A new compound that is highly sensitive to 5HT1A, will be used in PET imaging to measure the level of activity of these receptors and try to detect abnormalities. Changes in receptor activity may help determine where in the brain the seizures are originating. Additional PET scans will be done to measure the amount of blood flow to the brain and the rate at which the brain uses glucose-a sugar that is the brain's main fuel. Blood flow measurement is used to calculate the distribution of serotonin receptors, and glucose use helps determine how seizures affect brain function. The information gained from the study will be used to try to help guide the patient's therapy and determine if surgery might be beneficial in controlling the patient's seizures.
Detailed Description
Objective: to study serotonin receptors in patients with localization-related epilepsy. Studies in experimental animals have suggested that: Serotonin is an anticonvulsant neurotransmitter in a number of seizure models; its anticonvulsant action is mediated by activation of 5-HT(1A) receptors; drugs with antiepileptic effects may release 5HT or block reuptake, and these mechanisms appear to be related to their therapeutic effect. 5HT(1A) receptors are abundant in regions such as entorhinal cortex, hippocampus, and temporal neocortex, where epileptogenic zones are frequently found. Considerable evidence from literature indicates that alterations in 5-HT(1A) receptors exist in experimental models of both generalized and complex partial seizures. There is little data on changes in 5-HT receptors in epileptic patients. Study population: 75 patients with localization-related epilepsy and 20 normal controls, aged 18-60. Design: Using a new PET compound which is a highly selective 5-HT(1A) silent antagonist referred to as (18)FCWAY, we will attempt to detect abnormalities in serotonin receptors in vivo in patients with epilepsy. The patients will have (18)FCWAY serotonin receptor studies (which include (15)H2O-CBF PET) and high resolution T1-weighted MRI for co-registration. (18)FDG-PET will be performed in the patients as part of seizure focus localization. We will also test subjects for the serotonin transporter polymorphism associated with depression, and perform a standard depression battery. Outcome measures: 5HT-1A receptor binding and Glucose metabolism measured by PET.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Partial Epilepsy
Keywords
Epilepsy, Temporal Lobe, Blood Flow, Metabolism, Localization

7. Study Design

Enrollment
95 (false)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
INCLUSION CRITERIA: Patients must have clinically documented partial seizures with consistent EEG evidence as defined by the 1981 International Classification of Epileptic Seizures, refractory to standard antiepileptic treatment for at least one year. Patients will be in age ranges of 18 to 60. Patients may be male or female. Female patients of child bearing potential will have a pregnancy test prior to each PET scan to ensure that pregnant patients will not participate in the study. During the study, woman of child bearing potential must use a reliable method of birth control. Three groups of patients will be scanned: 50 patients with EEG and clinical evidence for mesial temporal onset with either MRI findings of mesial temporal sclerosis (MTS) or dysplasia or normal MRI studies. 25 patients with apparent neocortical seizure foci. In addition, patients will be screened for the presence of depression in addition to epilepsy; at least 15 patients from groups 1 and 2 who currently meet DSM-IV criteria for the category "Mood disorder due to epilepsy" (293.83), and the subtype "with major Depressive-Like Episode" 296.2 Major Depressive Disorder, Single Episode, or 296.3 Major Depressive Disorder, Recurrent, indicating that subjects meet diagnostic criteria for a major depressive episode. DSM diagnoses will be based on the Research Version of the Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID-I) including the detailed assessment of the course of both epilepsy and depressive symptoms as well as the family history of medical and psychiatric conditions. Twenty healthy normal adults will be included. Controls will be screened in the NINDS Clinical Epilepsy Section outpatient clinic, with physical examination, CBC urinalysis and blood chemistries. Controls with chronic illnesses, taking any medications, or who smoke will be excluded. They will be asked to abstain from alcohol for one week before the study. EXCLUSION CRITERIA: Patients younger than 18 or older than 60 years old will be excluded from the study. Patients with a known treatable seizure etiology such as neoplastic or infectious disease will be excluded. Patients with MRI findings consistent with brain tumors, trauma or AVMs will be excluded. Patients with progressive neurologic disorders. Patients with a history of significant medical disorders, or requiring chronic treatment with other drugs which can not be stopped, except for SSRIs. Patients with cancer. Patients not capable of giving an informed consent. Patients who had seizure activity 24 hours prior to the study.
Facility Information:
Facility Name
National Institutes of Health Clinical Center, 9000 Rockville Pike
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
8753673
Citation
Busatto GF. Radioligands for brain 5-HT2 receptor imaging in vivo: why do we need them? Eur J Nucl Med. 1996 Aug;23(8):867-70. doi: 10.1007/BF01084358. No abstract available.
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Serotonin Receptors in Seizure Disorders

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