Protocol Number: 02-N-0256

Title:

Role of Serum Gonadal and Neuroactive Steroids in the Seizure Susceptibility of Women with Catamenial Epilepsy

Number:

02-N-0256

Summary:

This study will measure and compare hormone levels in women with catamenial epilepsy (epilepsy in which seizures are more frequent during menstrual periods), women with seizures not related to their menstrual cycle, and normal control subjects. It will determine whether there are differences among the three groups in their hormone levels or in how fast the levels change. It will also examine what relationship, if any, exists between hormone changes and seizures in women with catamenial epilepsy. The hormones under study include the gonadal hormones estrone, estradiol and progesterone, and the neuroactive steroids allopregnanolone, pregnenolone, and dehydroepiandrosterone.

Women who meet the following criteria may be eligible for this 3-month study:

- Between 18 and 45 years of age, with catamenial epilepsy

- Between 18 and 45 years of age, with seizures, but not catamenial epilepsy

- Between 18 and 45 years of age, without seizures

All participants will have a physical examination at the beginning of the study, at each clinic visit, and at completion or withdrawal from the study. In addition, they will undergo the following procedures:

Baseline Monitoring

For the first 2 months, all participants will keep a diary of their temperature and onset of menses. Women with epilepsy will also record their seizures.

Electroencephalography (EEG)

Healthy volunteers will have a 45-minute EEG (recording of the electrical activity of the brain) at the beginning of each menstrual cycle and each day during the menses. Women with epilepsy will have continuous EEG monitoring for 8 days, beginning 5 days before their menstrual period is expected. The continuous monitoring can be done on an outpatient basis, using a portable EEG recording device, or as an inpatient, with admission to the hospital for the 8 days of recording.

Blood Sampling

All participants will have a small blood sample (2 teaspoons) drawn once a day on days 10, 14, 17, 19 and 21 of their menstrual cycle and three times a day on day 6 and for a period of 8 days, starting 5 days before the expected menses and continuing for 3 days of the next cycle. For the days with three blood draws, a small needle that can stay in place for up to 72 hours will be placed in the arm to avoid the discomfort of multiple needle sticks.

Sponsoring Institute:

National Institute of Neurological Disorders and Stroke (NINDS)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Female

Referral Letter Required: No

Population Exclusion(s): Male

Eligibility Criteria:

INCLUSION CRITERIA:

Group A subjects will be 8 women between 18 and 45 years of age who have complex partial seizures with Type 1 catamenial seizure exacerbation as previously defined.

Group B subjects will be 8 women between 18 and 45 years of age with complex partial seizures who do not meet the criteria for catamenial seizure exacerbations. The presence or absence of Type 1 catamenial seizure exacerbation will be documented by a standard seizure calendar self-reported for at least two consecutive menstrual cycles.

Patients receiving antiepileptic drug therapy will continue on their mediations.

All subjects must agree to use double barrier contraceptives, have an intrauterine device in place or practice abstinence during the course of the study.

Patients will be recruited from the epilepsy patient population at the National Institutes of Health.

Subjects in groups A and B will be matched for seizure frequency. Volunteers will be matched with the subjects in group A by age. In this pilot study, no attempt will be made to match patients according to anticonvulsant medications.

The patient will be properly informed of the nature and risks of the study and give informed consent in writing, prior to entering the study.

EXCLUSION CRITERIA:

Any of the following conditions are cause for exclusion from the study:

Any illness requiring chronic drug therapy other than antiepileptic drugs.

Any history of an illness likely to be adversely affected by the trial.

Psychiatric hospitalization lasting more than 2 months at any time prior to the study.

Use of tricyclic antidepressants within 4 weeks prior to randomization and/or anti-psychotic drugs within 2 weeks prior to randomization.

Children will not be included in this pilot study, because the profile of hormonal secretion undergoes profound changes during puberty.

Use of illicit drugs, alcoholism or binge drinking as per medical history inventory.

Women who are unwilling to use an alternative to oral contraceptives for contraception, (double barrier contraceptives, intrauterine device or abstinence), and establish that they are currently not pregnant by submitting to a pregnancy test.

Exposure to any other investigational drug within 12 weeks prior to randomization.

Any history of endocrine dysfunction.

Women will be excluded if they do not have regular menstrual cycle intervals between 27 and 32 days or if they are pregnant, nursing or taking oral contraceptives or other reproductive hormones.

If a need should arise to change the antiepileptic regime during the study this subject will be excluded and replaced with another patient.

Women currently taking Phenobarbital or another barbiturate.

Women who are unwilling to refrain from strenuous exercise during the study.

Women who are unwilling to refrain from usage of herbal and soy products.

Special Instructions: Currently Not Provided

Keywords:

Neurosteroids

Complex Partial Seizure

Menstrual Cycle

Allopregnanolone

Catamenial Epilepsy

Recruitment Keywords:

Seizures

Epilepsy

Catamenial Epilepsy

Healthy Volunteer

HV

Normal Control

Conditions:

Epilepsy

Investigational Drug(s):

None

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Berga SL Understanding premenstrual syndromeLancet 1998 Feb 14;351(9101):465-6 No abstract available

Herzog AG Progesterone therapy in women with complex partial and secondary generalizedseizuresNeurology 1995 Sep;45(9):1660-2

Herzog AG, Klein P, Ransil BJ Three patterns of catamenial epilepsyEpilepsia 1997 Oct;38(10):1082-8

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
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