The National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, is looking for individuals to participate in clinical studies. Participating in clinical trials allows you to play an active role in research on the nature and causes of many disorders of the brain and nervous system, and to possibly help physician-scientists develop future treatments. The information below is designed to help you quickly learn about actively recruiting research studies for which you or someone you know may be eligible.

Description:

The purpose of this study (11-N-0039) is to find out if an experimental drug called PRX-00023 reduces the frequency of seizures in people with localization-related epilepsy. Localization-related epilepsy is a type of epilepsy that starts in only one part of the brain.

The brain chemical serotonin helps nerve cells communicate. Previous research suggests that serotonin activity may be lower in brain areas where seizures start. Increasing activity at the receptor site on nerve cells that bind serotonin may help prevent seizures. In the study, researchers will use PRX-00023—which attaches to serotonin receptors and increases serotonin activity—to test if the drug can reduce seizure frequency in people whose seizures are not well-controlled with anti-seizure medication.

Thirty people with localization-related epilepsy will participate in this study. The study is comprised of six phases, and requires 9 visits to the NIH Clinical Center in Bethesda, MD—over an approximately 34-week period. All study visits will take place at the NIH Clinical Center.

In phase 1, volunteers will be screened to determine eligibility. Screening will include information collected from protocol 01-N-0139, a routine screening protocol, as well as medical history, a physical examination, an electroencephalogram (EEG), and blood and urine testing.

In phase 2, researchers will observe and evaluate how frequently participants’ seizures occur before they begin the study medication. Participants will have mood, learning, and memory tests, and a PET scan, and be given a calendar to track seizures for 6 weeks. Some participants may also have an EEG and be asked to provide a saliva sample for genetic testing.

In phase 3—the first study medication phase—each participant will receive either the study medication (PRX-00023) or a placebo (inactive medication) for 12 weeks. Participants will keep a calendar to track their seizures, response to the medication, and any side effects. During the study visit, participants will have a physical examination, blood test, and an electrocardiogram (ECG).

At the phase 4 interim period, participants will have a study visit which will include an ECG and neuropsychological and mood rating tests. Researchers will gradually decrease the study medication dosage over a 10-day period and then stop the medication completely. Participants will then go through a washout period in which they will stay off of the study medication for 2-3 weeks.

In phase 5, participants will begin the second study medication phase for another 12-week period. If participants received study medication during phase 3, they will receive placebo during phase 5. If participants received placebo during phase 3, then they will receive study medication during phase 5.

In phase 6, one month after study medication has stopped, participants will return to the NIH Clinical Center for follow-up evaluation which will include a physical exam, ECG, blood, urine tests, and mood tests.

Eligibility Criteria:

INCLUSION CRITERIA:

  1. Enrolled in protocol 01-N-0139
  2. Age 18 to 65
  3. Localization-related epilepsy diagnosed by standard clinical criteria that has not responded to treatment with up to two standard antiepileptic drugs either sequentially or in combination.
  4. Patients must be able to provide informed consent.
  5. Patients must be able to remain on their baseline AED drugs and doses for the duration of the study
  6. Patients must be able to use seizure calendars to record seizures throughout the trial.
  7. Experiences 4 seizures within a 6-week period

 

EXCLUSION CRITERIA:

  1. Pregnancy or lactation
  2. Women of child-bearing potential and men who are unable or unwilling to take adequate contraceptive precautions, including one of the following: - hormonal contraception (birth control pills, injected hormones or vaginal ring); - intrauterine device; - barrier methods (condom or diaphragm) combined with spermicide; - surgical sterilization (hysterectomy, tubal ligation, or vasectomy in a partner
  3. Current treatment for another significant medical disorder, such as diabetes, or heart disease, or an untreated disorder, that is discovered during the screening examination and might interfere with the study and is determined by the PI to warrant exclusion of the participant.
  4. An abnormality on clinical laboratory tests, physical examination, EEG or ECG that might increase the risk associated with trial participation or investigational product administration, such as hepatic enzyme elevation greater than twice normal, or hematocrit lower than 30.
  5. A level 4 or 5 on the Columbia Suicide Severity Rating Scale rating for symptoms during the last month
  6. Concomitant treatment with more than 2 AEDs
  7. Evidence for a potentially progressive neurologic disorder, such as an astrocytoma 8. Use of sublingual lorazepam for seizure clusters more than once per wee 9. Use of any of the following prohibited medications/classes with less than required interval period: - Any other Investigational drugs; required interval period (weeks prior to baseline) is 4 - benzodiazepines; required interval period (weeks prior to baseline) is 4 - MAO Inhibitors anti depressant; required interval period (weeks prior to baseline) is 4 - Buspirone; required interval period (weeks prior to baseline) is 2 - other psychotropic medicines; required interval period (weeks prior to baseline) is 2 - potent CYP3A4 inducers/inhibitors; required interval period (weeks prior to baseline) is 2 for: - Itraconazole - ketoconazole - HIV antivirals - clarithromycin - phenytoin - Prornolol is 2

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Study Location:

Maryland