Progesterone vs Placebo Therapy for Women With Epilepsy

• Number of women who show a >50% decline in average daily seizure frequency for the most severe seizure type. [ Time Frame: 9 years ] [ Designated as safety issue: Yes ]
• Number of women who show a greater than 50% decline in average daily seizure frequency for secondary generalized, complex partial and simple partial seizures considered separately [ Time Frame: 9 years ] [ Designated as safety issue: Yes ]
• Number of women who show a decline in average daily seizure frequency. [ Time Frame: 9 years ] [ Designated as safety issue: Yes ]
• Change in average daily seizure frequency during the entire cycle. [ Time Frame: 9 years ] [ Designated as safety issue: Yes ]
• Change in average daily seizure frequency during the period of progesterone use (Day 14 to -1) and no progesterone use (Day 1 to 13). [ Time Frame: 9 years ] [ Designated as safety issue: No ]
• Change in seizure severity on treatment versus baseline. [ Time Frame: 9 years ] [ Designated as safety issue: No ]
• Change in quality of life score. [ Time Frame: 9 years ] [ Designated as safety issue: No ]
• Association of change in seizure frequency with changes in serum levels of progesterone, allopregnanolone, estradiol and estradiol/progesterone. [ Time Frame: 9 years ] [ Designated as safety issue: No ]
• Association of change in seizure frequency with changes in serum levels of antiepileptic drugs [ Time Frame: 9 years ] [ Designated as safety issue: Yes ]

There is considerable evidence to suggest that natural progesterone has anti-seizure properties. The purpose of this study is to determine if progesterone supplement during the second half of the menstrual cycle lessens seizure frequency in women with epilepsy.

This is a 6-month study. The first 3 months will gather baseline information on seizures, antiepileptic drug levels , menstrual cycles, hormone levels, emotional function, and quality of life. The second 3 months will assess the effects of treatment on these parameters.

• Experimental: 1
  Progesterone Lozenges
  Intervention: Biological: Natural Progesterone
• Placebo Comparator: 2
  Matched Placebo
  Intervention: Biological: Natural Progesterone

• Herzog AG, Harden CL, Liporace J, Pennell P, Schomer DL, Sperling M, Fowler K, Nikolov B, Shuman S, Newman M. Frequency of catamenial seizure exacerbation in women with localization-related epilepsy. Ann Neurol. 2004 Sep;56(3):431-4.
• Herzog AG. Progesterone therapy in women with complex partial and secondary generalized seizures. Neurology. 1995 Sep;45(9):1660-2.
• Herzog AG. Progesterone therapy in women with epilepsy: a 3-year follow-up. Neurology. 1999 Jun 10;52(9):1917-8. No abstract available.
• Herzog AG, Klein P, Ransil BJ. Three patterns of catamenial epilepsy. Epilepsia. 1997 Oct;38(10):1082-8.

INCLUSION:

1. Subject must be between the ages of 13 and 45.
2. Subject must have a history of seizures (documented by EEG).
3. Subject must have had at least 2 seizures or auras per month during the past 3 months.
4. Subject must be on stable antiepileptic drug therapy for at least 2 months.
5. Subject must have cycle intervals between 21 and 35 days during 6 months prior to entry.

EXCLUSION:

1. Subject that is pregnant or lactating.
2. Subject that is on major tranquilizers, antidepressant medications, or reproductive hormones.
3. Subject that is unable to document seizures.

• Brigham and Women's Hospital
• Columbia University
• Dartmouth-Hitchcock Medical Center
• Emory University
• Johns Hopkins University
• MINCEP Epilepsy Care
• Montreal Neurological Institute and Hospital
• Ohio State University
• Thomas Jefferson University
• University of Maryland
• University of Southern California
• University of Virginia
• Weill Medical College of Cornell University