EpilepsyNCT00931619
GABA/Glutamate Balance in Temporal Lobe Epilepsy With and Without Major Depression
An observational study of Epilepsy and Epilepsy, Temporal Lobe, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
Objective: To study the relative balance of GABA (A) binding potential and glutamate utilization in subjects with localization-related epilepsy with and without depression, subjects with major depressive disorder alone, and in subjects with generalized epilepsy (expected not to have significant comorbid depression). Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Epilepsy, Epilepsy, Temporal Lobe, Depression
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Jun 2009to 2 Apr 2013
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male and female subjects aged between 18 and 55 years
- Epileptic patients must have clinically documented partial seizures, in either the left or right temporal lobe, or generalized 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. This criterion will be established by preliminary screening in the NINDS CES outpatient clinic, and, where previous studies are not adequate, by inpatient video-EEG monitoring.
- All subjects with epilepsy must exhibit seizures not adequately controlled by medication alone, despite adequate trials of multiple agents.
- Subjects with epilepsy must currently be taking an AED which exerts its primary method of action on a system other than GABA. Examples include sodium or calcium channel blockers (phenytoin, carbamazepine, oxcarbazepine, lamotrigine, zonisamide, and ethosuximide), drugs that bind to SV2A sites (levetiracetam), or drugs which bind to the alpha2delta subunit of calcium channels (gabapentin and pregbalin). Patients on AEDs that have direct effects on GABA and glutamate (vigabatrin, phenobarbital, benzodiazepines, tiagabine) will be excluded. No subject s medication will be changed for the purpose of inclusion in this study.
- Patients with TLE and depression must 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.
- Patients with MDD alone must currently meet DSM-IV criteria for Major Depressive Disorder, and also have either a family history of mood disorders, or a history of multiple major depressive episodes.
- Healthy control subjects who do not meet criteria for any DSM-IV axis I psychiatric disorder, and have no family history (in first degree relatives) of a mood or anxiety disorder will also be recruited.
- Subjects must be able to give written informed consent prior to participation in this study.
Who cannot join
- Subjects with major medical or neurological disorders (besides TLE or generalized epileptiform disorder) expected to influence cerebral blood flow or morphology
- Subjects with epilepsy taking any medications (other than antiepileptic drugs) that may affect cerebral blood flow, GABA or glutamate neurotransmission, or metabolism.
- Subjects with epilepsy taking AED s known to exert direct effects on GABA or glutamate.
- Subjects with epilepsy with depression who have taken anti-depressant drugs within 2 weeks of the study (4 weeks for fluoxetine)
- Medically healthy depressed subjects who have taken any drugs, including anti-depressants, expected to influence cerebral blood flow, metabolism, or morphology within 2 weeks of the study (4 weeks for fluoxetine)
- Healthy subjects who are taking any medications expected to influence cerebral blood flow, metabolism, or morphology.
Show all 15Show fewer
- Healthy subjects must be free from a personal history of seizure disorders
- In order to exclude subjects at-risk for the development of a mood disorder, healthy control subjects must be free from either a personal or family history (first-degree relatives) of Axis I psychiatric disorders
- Subjects with a history of drug or alcohol abuse within one year, or a lifetime history of alcohol or drug dependence (DSM-IV criteria). Subjects who consume an excessive amount of alcohol (more than 7 drinks per week for women, more than 14 drinks per week for men) will also be excluded.
- Subjects with structural lesions visible on MRI, excluding mesial temporal sclerosis
- Subjects with suicidal ideation, or a past history of suicide attempts
- Subjects with psychotic symptoms
- Subjects in whom MRI is contraindicated
- Female subjects who are lactating or pregnant
- Subjects with an IQ of less than 80 will be excluded from the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Objective: To study the relative balance of GABA (A) binding potential and glutamate utilization in subjects with localization-related epilepsy with and without depression, subjects with major depressive disorder alone, and in subjects with generalized epilepsy (expected not to have significant comorbid depression). Pilot data shows that GABA(A) binding potential and glutamate utilization are tightly coupled in healthy subjects particularly in the mesial temporal lobe. We hypothesize that subjects with epilepsy will not exhibit the same degree of coupling, and that subjects with both epilepsy and depression will exhibit an even more pronounced decoupling.
Study Population: Subjects aged 18-55 with localization-related epilepsy with and without depression, subjects with generalized epilepsy, subjects with major depressive disorder (MDD) alone, and healthy controls.
Read more
Design: This is a neuroimaging study, using positron emission tomography (PET) with [11C]flumazenil, to measure GABA(A) binding potential, and [18F]fluorodeoxyglucose, to measure glucose utilization (reflective of neuronal glutamate release) Magnetic resonance spectroscopy (MRS), will be used to measure GABA and glutamate in the mesial temporal cortex, and corroborate the PET results. Structural magnetic resonance images (MRI) will be obtained for MRS localization and partial volume correction of PET images.
Outcome measures: The binding potential of GABA(A), the regional rate of glucose metabolism, and the levels of GABA and glutamate as measured by MRS. Patients will be stratified by seizure type and depression ratings.
...
Read the detailed description
Objective: To study the relative balance of GABA (A) binding potential and glutamate utilization in subjects with localization-related epilepsy with and without depression, subjects with major depressive disorder alone, and in subjects with generalized epilepsy (expected not to have significant comorbid depression). Pilot data shows that GABA(A) binding potential and glutamate utilization are tightly coupled in healthy subjects, particularly in the mesial temporal lobe. We hypothesize that subjects with epilepsy will not exhibit the same degree of coupling, and that subjects with both epilepsy and depression will exhibit an even more pronounced decoupling.
Study Population: Subjects aged 18-55 with localization-related epilepsy without clinically significant depression, subjects with generalized epilepsy, and healthy controls.
Design: This is a neuroimaging study, using positron emission tomography (PET) with [11C]flumazenil, to measure GABA(A) binding potential, and [18F]fluorodeoxyglucose, to measure glucose utilization (reflective of neuronal glutamate release). Magnetic resonance spectroscopy (MRS) will be used to measure GABA and glutamate in the mesial temporal cortex and corroborate the PET results. Structural magnetic resonance images (MRI) will be obtained for MRS localization and partial volume correction of PET images.
Outcome measures: The binding potential of GABA(A), the regional rate of glucose metabolism, and the levels of GABA and glutamate as measured by MRS. Patients will be stratified by seizure type.
- Keywords
- Fluorine-18 Fluorodeoxyglucose, Epilepsy, Epileptic Focus, Temporal Lobe Epilepsy, Depression, Major Depressive Disorder, Healthy Volunteer, HV
- Medical subject headings
- Epilepsy, Epilepsy, Temporal Lobe, Depression, Depressive Disorder, Major
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome measures will include GABA(A) binding potential and regional glucose metabolic rate as measured by PET, and GABA and glutamate levels as measured by MRS.
Secondary outcomes (1)
Secondary outcome measures will include brain structure on MRI, blood oxygenation level dependent contrast in functional resting state scans, genetic data, and scores on depression rating scales.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2009 (estimated)
- Study start29 Jun 2009
- Study completion2 Apr 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for EpilepsyStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Time perspective
- Prospective
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Investigators
- William H Theodore, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00931619
- Sponsor's protocol ID
- 090182
- Other IDs
- 09-N-0182
- Status last verified
- 2 Apr 2013
- First submitted
- 1 Jul 2009
- Last updated
- 17 Dec 2019
- Results posted
- No
Publications
Baker GA, Nashef L, van Hout BA. Current issues in the management of epilepsy: the impact of frequent seizures on cost of illness, quality of life, and mortality. Epilepsia. 1997;38 Suppl 1:S1-8. doi: 10.1111/j.1528-1157.1997.tb04511.x.
PubMed 9092951Hanai T. Quality of life in children with epilepsy. Epilepsia. 1996;37 Suppl 3:28-32. doi: 10.1111/j.1528-1157.1996.tb01816.x.
PubMed 8681908Leidy NK, Elixhauser A, Vickrey B, Means E, Willian MK. Seizure frequency and the health-related quality of life of adults with epilepsy. Neurology. 1999 Jul 13;53(1):162-6. doi: 10.1212/wnl.53.1.162.
PubMed 10408553Nugent AC, Martinez A, D'Alfonso A, Zarate CA, Theodore WH. The relationship between glucose metabolism, resting-state fMRI BOLD signal, and GABAA-binding potential: a preliminary study in healthy subjects and those with temporal lobe epilepsy. J Cereb Blood Flow Metab. 2015 Mar 31;35(4):583-91. doi: 10.1038/jcbfm.2014.228.
PubMed 25564232
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- GABA/Glutamate Balance in Temporal Lobe Epilepsy With and Without Major Depression
- ClinicalTrials.gov ID
- NCT00931619
- Acronym / sponsor ID
- 090182
- Keywords
- Fluorine-18 Fluorodeoxyglucose, Epilepsy, Epileptic Focus, Temporal Lobe Epilepsy, Depression, Major Depressive Disorder, Healthy Volunteer, HV
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 29 Jun 2009
- Study completion
- 2 Apr 2013
- First posted
- 2 Jul 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Objective: To study the relative balance of GABA (A) binding potential and glutamate utilization in subjects with localization-related epilepsy with and without depression, subjects with major depressive disorder alone, and in subjects with generalized epilepsy (expected not to have significant comorbid depression). Pilot data shows that GABA(A) binding potential and glutamate utilization are tightly coupled in healthy subjects particularly in the mesial temporal lobe. We hypothesize that subjects with epilepsy will not exhibit the same degree of coupling, and that subjects with both epilepsy and depression will exhibit an even more pronounced decoupling.
Study Population: Subjects aged 18-55 with localization-related epilepsy with and without depression, subjects with generalized epilepsy, subjects with major depressive disorder (MDD) alone, and healthy controls.
Design: This is a neuroimaging study, using positron emission tomography (PET) with [11C]flumazenil, to measure GABA(A) binding potential, and [18F]fluorodeoxyglucose, to measure glucose utilization (reflective of neuronal glutamate release) Magnetic resonance spectroscopy (MRS), will be used to measure GABA and glutamate in the mesial temporal cortex, and corroborate the PET results. Structural magnetic resonance images (MRI) will be obtained for MRS localization and partial volume correction of PET images.
Outcome measures: The binding potential of GABA(A), the regional rate of glucose metabolism, and the levels of GABA and glutamate as measured by MRS. Patients will be stratified by seizure type and depression ratings.
...
Detailed description
Objective: To study the relative balance of GABA (A) binding potential and glutamate utilization in subjects with localization-related epilepsy with and without depression, subjects with major depressive disorder alone, and in subjects with generalized epilepsy (expected not to have significant comorbid depression). Pilot data shows that GABA(A) binding potential and glutamate utilization are tightly coupled in healthy subjects, particularly in the mesial temporal lobe. We hypothesize that subjects with epilepsy will not exhibit the same degree of coupling, and that subjects with both epilepsy and depression will exhibit an even more pronounced decoupling.
Study Population: Subjects aged 18-55 with localization-related epilepsy without clinically significant depression, subjects with generalized epilepsy, and healthy controls.
Design: This is a neuroimaging study, using positron emission tomography (PET) with [11C]flumazenil, to measure GABA(A) binding potential, and [18F]fluorodeoxyglucose, to measure glucose utilization (reflective of neuronal glutamate release). Magnetic resonance spectroscopy (MRS) will be used to measure GABA and glutamate in the mesial temporal cortex and corroborate the PET results. Structural magnetic resonance images (MRI) will be obtained for MRS localization and partial volume correction of PET images.
Outcome measures: The binding potential of GABA(A), the regional rate of glucose metabolism, and the levels of GABA and glutamate as measured by MRS. Patients will be stratified by seizure type.
Study design
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Male and female subjects aged between 18 and 55 years
- Epileptic patients must have clinically documented partial seizures, in either the left or right temporal lobe, or generalized 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. This criterion will be established by preliminary screening in the NINDS CES outpatient clinic, and, where previous studies are not adequate, by inpatient video-EEG monitoring.
- All subjects with epilepsy must exhibit seizures not adequately controlled by medication alone, despite adequate trials of multiple agents.
- Subjects with epilepsy must currently be taking an AED which exerts its primary method of action on a system other than GABA. Examples include sodium or calcium channel blockers (phenytoin, carbamazepine, oxcarbazepine, lamotrigine, zonisamide, and ethosuximide), drugs that bind to SV2A sites (levetiracetam), or drugs which bind to the alpha2delta subunit of calcium channels (gabapentin and pregbalin). Patients on AEDs that have direct effects on GABA and glutamate (vigabatrin, phenobarbital, benzodiazepines, tiagabine) will be excluded. No subject s medication will be changed for the purpose of inclusion in this study.
- Patients with TLE and depression must 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.
Key exclusion criteria (15 listed)
- Subjects with major medical or neurological disorders (besides TLE or generalized epileptiform disorder) expected to influence cerebral blood flow or morphology
- Subjects with epilepsy taking any medications (other than antiepileptic drugs) that may affect cerebral blood flow, GABA or glutamate neurotransmission, or metabolism.
- Subjects with epilepsy taking AED s known to exert direct effects on GABA or glutamate.
- Subjects with epilepsy with depression who have taken anti-depressant drugs within 2 weeks of the study (4 weeks for fluoxetine)
- Medically healthy depressed subjects who have taken any drugs, including anti-depressants, expected to influence cerebral blood flow, metabolism, or morphology within 2 weeks of the study (4 weeks for fluoxetine)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
The primary outcome measures will include GABA(A) binding potential and regional glucose metabolic rate as measured by PET, and GABA and glutamate levels as measured by MRS.
1 secondary outcome
Secondary outcome measures will include brain structure on MRI, blood oxygenation level dependent contrast in functional resting state scans, genetic data, and scores on depression rating scales.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2019.
- Background: PubMed 9092951Baker GA, Nashef L, van Hout BA. Current issues in the management of epilepsy: the impact of frequent seizures on cost of illness, quality of life, and mortality. Epilepsia. 1997;38 Suppl 1:S1-8. doi: 10.1111/j.1528-1157.1997.tb04511.x.
- Background: PubMed 8681908Hanai T. Quality of life in children with epilepsy. Epilepsia. 1996;37 Suppl 3:28-32. doi: 10.1111/j.1528-1157.1996.tb01816.x.
- Background: PubMed 10408553Leidy NK, Elixhauser A, Vickrey B, Means E, Willian MK. Seizure frequency and the health-related quality of life of adults with epilepsy. Neurology. 1999 Jul 13;53(1):162-6. doi: 10.1212/wnl.53.1.162.
- Derived from this study: PubMed 25564232Nugent AC, Martinez A, D'Alfonso A, Zarate CA, Theodore WH. The relationship between glucose metabolism, resting-state fMRI BOLD signal, and GABAA-binding potential: a preliminary study in healthy subjects and those with temporal lobe epilepsy. J Cereb Blood Flow Metab. 2015 Mar 31;35(4):583-91. doi: 10.1038/jcbfm.2014.228.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William H Theodore, M.D. principal investigator
National Institute of Neurological Disorders and Stroke (NINDS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Epilepsy and Epilepsy, Temporal Lobe, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary outcome measures will include GABA(A) binding potential and regional glucose metabolic rate as measured by PET, and GABA and glutamate levels as measured by MRS.. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00931619, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2019.