Brain Infusion of Muscimol to Treat Epilepsy

NCT00005925 | Terminated Phase 1

• 2 other identifiers: 00015800-N-0158
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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. 1.Computerized tomography (CT) and magnetic resonance imaging (MRI) of the head to guide catheter/electrode placement (see #2).
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. 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. 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. 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. 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.

Conditions

Epilepsy

Keywords

Video-EEG; Muscimol; Depth Electrode; Brain Catheter; Pharmacology; Epilepsy; Infusion; Magnetic Resonance Imaging

Interventions

Muscimol DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be eligible for entry into the study, candidates must meet all the following criteria:
• Be 18 years of age or older.
• Have simple or complex partial seizures.
• Seizures must persist at 2 or more per month, despite medical therapy.
• Be able to give informed consent.
• Have been determined by the NIH neurology staff to have medically intractable epilepsy.
• Have a seizure focus in a single region of one cerebral hemisphere.

You may not qualify if:

• Candidates will be excluded if they:
• Are pregnant.
• Have a contraindication to MRI scanning.
• Have a bleeding disorder that cannot be corrected before testing or treatment.
• Are unable to comprehend the risks of the testing and surgical therapy.
• Have seizure foci in more than one region of one hemisphere or in both cerebral hemispheres.
• Have a positive HIV test, because such patients would have increased risk of infection due to their immune deficiency.

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Sperling MR, Feldman H, Kinman J, Liporace JD, O'Connor MJ. Seizure control and mortality in epilepsy. Ann Neurol. 1999 Jul;46(1):45-50. doi: 10.1002/1531-8249(199907)46:13.0.co;2-i.

  PMID: 10401779 BACKGROUND

• Eder HG, Jones DB, Fisher RS. Local perfusion of diazepam attenuates interictal and ictal events in the bicuculline model of epilepsy in rats. Epilepsia. 1997 May;38(5):516-21. doi: 10.1111/j.1528-1157.1997.tb01134.x.

  PMID: 9184595 BACKGROUND

• Brailowsky S, Silva-Barrat C, Menini C, Riche D, Naquet R. Effects of localized, chronic GABA infusions into different cortical areas of the photosensitive baboon, Papio papio. Electroencephalogr Clin Neurophysiol. 1989 Feb;72(2):147-56. doi: 10.1016/0013-4694(89)90176-4.

  PMID: 2464486 BACKGROUND

• Heiss JD, Walbridge S, Morrison P, Hampton RR, Sato S, Vortmeyer A, Butman JA, O'Malley J, Vidwan P, Dedrick RL, Oldfield EH. Local distribution and toxicity of prolonged hippocampal infusion of muscimol. J Neurosurg. 2005 Dec;103(6):1035-45. doi: 10.3171/jns.2005.103.6.1035.

  PMID: 16381190 BACKGROUND

MeSH Terms

Conditions

Epilepsy

Interventions

Muscimol

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Oxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Mycotoxins; Toxins, Biological; Biological Factors

Study Officials

• John D Heiss, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2000
• First Posted: June 26, 2000
• Study Start: June 23, 2000
• Study Completion: December 24, 2014
• Last Updated: July 5, 2018

Record last verified: 2014-12-24

Locations

US (1)