| City: |
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Bethesda |
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State:
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MD |
| Zip Code: |
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20892 |
| Conditions: |
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Epilepsy |
| Purpose: |
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This study will examine the safety and effectiveness of infusing a chemical called muscimol
into the brain to control seizures in patients with intractable epilepsy (frequent seizures
that persist despite therapy). Muscimol, which is similar to a naturally occurring brain
chemical called GABA, has been shown to reduce seizures in rats. After the infusion study,
patients will undergo a standard surgical procedure for controlling seizures.
Patients 18 years of age or older with intractable epilepsy may be eligible for this study.
Before entering protocol 00-N-0158, candidates will be screened under protocol 01-N-0139,
Evaluation and Treatment of Patients with Epilepsy, with a medical history, physical and
neurologic examination, chest X-ray, electrocardiogram, blood and urine tests,
electroencephalographic (EEG) monitoring and magnetic resonance imaging (MRI) of the head.
Patients enrolled in this study will have the following procedures:
1. Computerized tomography (CT) and magnetic resonance imaging (MRI) of the head to guide
catheter/electrode placement (see #2).
2. Depth catheter/electrode placement into the presumed location of the seizure focus (the
part of the brain where the seizures originate) - A small hole is drilled through the
skull. A depth electrode with a hole in the center of the tubing is passed through the
brain into the structures usually involved in intractable epilepsy. MRI will be done to
check electrode placement. Video-EEG monitoring will continue for 5 days for this part
of the study. Patients will be tested for their ability to understand and produce
speech, see normally, move their arms and legs, distinguish sharp and dull objects, and
put pegs in a pegboard. They will be questioned about headache, weakness, numbness or
sleepiness. The electrode will be left in place for muscimol infusion (see #3).
3. Muscimol infusion - Into the seizure focus, patients will be given two infusions-one of
saline (salt water) alone and one of muscimol diluted in saline. Each infusion will be
given over a period of one-half to 5 1/2 days, infused at the rate of 0.1 ml (1/50th of
a teaspoon) per hour. During the infusions video-EEG recordings will continue and
patients will be interviewed and examined as described in #2 above).
4. Blood testing - About 2 tablespoons of blood will be drawn daily during the testing
period and for the first 2 days after surgery (see #5).
5. Surgery - Temporal lobectomy or topectomy (removal of a small, specific area of brain
tissue) is the standard surgical treatment for medically intractable epilepsy whose
seizure focus is not in a critical brain region, such as an area that controls
language, movement, or sensation. If the patient's seizures arise from one of these
areas, an alternative procedure called multiple subpial transection will be offered. In
this procedure, vertical cuts are made in the seizure focus to prevent neurons (nerve
cells that transmit electrical impulses) in the focus from spreading the seizure to the
rest of the brain.
6. Surgery follow-up - Patients will be monitored in the surgical intensive care unit for
24 to 48 hours and then in the NINDS nursing unit for 4 to 8 days before being
discharged to home. Another visit in the NINDS outpatient clinic will be scheduled for
6-12 weeks after surgery.
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| Study summary: |
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Objectives: The objectives of this study are to test the hypotheses that direct infusion of
the brain (convection enhanced delivery) with neurotransmitter receptor agonists is 1) safe
and 2) can be used to study the basic pathophysiology of the epileptic focus in human
subjects. The approach described may be a new approach for precise localization of a
seizure focus. It may also prove to indicate the distribution of suppression (in space)
required for elimination of seizure activity in individual patients and, by doing so, may
more accurately define the minimum treatment area that is required for success. Finally,
the data obtained may support the treatment of patients with medically intractable epilepsy
with neurotransmitter-specific agents infused directly into the epileptic focus.
Study Population: The study population will include adult patients with medically
intractable epilepsy who are candidates for surgical resection of their epileptic region.
Design: Adult patients who are candidates for standard surgical care for medically
intractable epilepsy will undergo standard noninvasive evaluation to identify the location
of the seizure focus. After surface EEG confirms the side and approximate location of the
seizure focus, a depth electrode with a central lumen will be placed in the seizure focus
for the purpose of this research study. The lumen in the depth electrode will be used to
deliver vehicle (artificial cerebrospinal fluid) or muscimol, a neurotransmitter
(gamma-aminobutyric acid, GABA) receptor agonist that suppresses neuronal activity. During
the infusion trials, patients will be monitored by neurologic examination and by video-EEG.
Following the trials, the epileptic focus will be resected, which is standard care for
medically intractable epilepsy, and the surgical specimen will be examined for any
histological changes caused by the infusions.
Outcome Measures: Basic pathophysiology of the epileptic focus will be examined by
assessing the effect of the infusion on seizure frequency (the primary end point), EEG
recordings, motor function, and visual object naming. Safety will be assessed by neurologic
examination and by pathologic examination (gross and microscopic) of the resected surgical
specimen (presence or absence of infusion-induced injury). |
| Criteria: |
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- INCLUSION CRITERIA:
To be eligible for entry into the study, candidates must meet all the following criteria:
1. Be 18 years of age or older.
2. Have simple or complex partial seizures.
3. Seizures must persist at 6 or more per month, despite medical therapy.
4. Be able to give informed consent.
5. Have been determined by the NIH neurology staff to have medically intractable
epilepsy.
6. Have a seizure focus in a single region of one cerebral hemisphere.
EXCLUSION CRITERIA:
Candidates will be excluded if they:
1. Are pregnant.
2. Have a contraindication to MRI scanning.
3. Have a bleeding disorder that cannot be corrected before testing or treatment.
4. Are unable to comprehend the risks of the testing and surgical therapy.
5. Have seizure foci in more than one region of one hemisphere or in both cerebral
hemispheres.
6. Have a positive HIV test, because such patients would have increased risk of
infection due to their immune deficiency. |
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| Study is available at: |
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National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, MD 20892
United States
Primary Contact:
Patient Recruitment and Public Liaison Office
Email: prpl@mail.cc.nih.gov
Phone: (800) 411-1222 |
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If you are interested in this clinical trial please use the contact information above. If you would like to get additional information about this clinical trial please visit ClinicalTrials.gov.
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| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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March 21, 2011 |
Modifications to
this listing: |
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Only selected fields are shown, please use the link
above to view all information about this clinical trial. |
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