Ignite Creation Date:
2024-05-05 @ 11:08 AM
Last Modification Date:
2024-10-26 @ 9:05 AM
Study NCT ID:
NCT00005925
Status:
TERMINATED
Last Update Posted:
2018-07-05
First Post:
2000-06-24
Brief Title:
Brain Infusion of Muscimol to Treat Epilepsy
Sponsor:
National Institute of Neurological Disorders and Stroke NINDS
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Trial of Intracerebral Infusion in Patients With Medically Intractable Epilepsy
Status:
TERMINATED
Status Verified Date:
2014-12-24
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 catheterelectrode placement see 2
2 Depth catheterelectrode 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 12 days infused at the rate of 01 ml 150th 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 patients 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
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 catheterelectrode placement see 2
2 Depth catheterelectrode 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 12 days infused at the rate of 01 ml 150th 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 patients 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
Detailed Description:
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
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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 00-N-0158 | None | None | None |