Progesterone vs Placebo Therapy for Women With Epilepsy

Phase 3 Study of Progesterone vs Placebo Therapy

The purpose of this investigation was to determine if cyclic adjunctive progesterone supplement is superior to placebo in the treatment of intractable seizures in women with and without catamenial epilepsy.

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Biological: Progesterone Lozenges; Other: Matched Placebo Lozenges

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 294
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3A 2B4
      • Montreal Neurological Institute
• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California, Keck School of Medicine
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Bayview Medical Center; Johns Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center, Harvard Neuroendocrine Unit
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55416
      • MINCEP Epilepsy Care
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • New York
    • New York, New York, United States, 10032
      • Columbia Medical Center
    • New York, New York, United States, 10021
      • New York Presbyterian Hospital- Weill Medical College of Cornell University, Comprehensive Epilepsy Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital, Comprehensive Epilepsy Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 11 years to 43 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.
4. Subject that has progressive neurological or systemic disorder or > 2-fold elevation in liver enzyme levels

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Catamenial Epilepsy: Progesterone Lozenges; Subjects with catamenial epilepsy received 200 mg progesterone lozenges	Biological: Progesterone Lozenges; 200mg Progesterone Lozenges
Placebo Comparator: Catamenial Epilepsy: Placebo Lozenges; Subjects with catamenial epilepsy received matched placebo lozenges	Other: Matched Placebo Lozenges; Matched Placebo Lozenges
Experimental: Noncatamenial Epilespy:Progesterone Lozenges; Subjects without catamenial epilepsy received 200 mg progesterone lozenges	Biological: Progesterone Lozenges; 200mg Progesterone Lozenges
Placebo Comparator: Noncatamenial Epilespy: Placebo Lozenges; Subjects without catamenial epilepsy received matched placebo lozenges	Other: Matched Placebo Lozenges; Matched Placebo Lozenges

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Women Who Show a Greater Than 50% Decline in Average Daily Seizure Frequency	Percent of women who show a greater than 50% decline in average daily seizure frequency	9 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Women Who Show a >50% Decline in Average Daily Seizure Frequency for the Most Severe Seizure Type.	Percent of women who show a >50% decline in average daily seizure frequency for the most severe seizure type.	9 years
Percentage 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	Percentage 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	9 years
Changes in Serum Progesterone Levels in Subjects at Baseline and After Treatment.	Changes in serum progesterone levels in subjects at baseline and after treatment with progesterone or placebo.	9 years
Change in Serum Levels of Antiepileptic Drugs on Progesterone and Placebo for Subjects With Catamenial and Non-catamenial Epilepsy.		9 years

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Collaborators: Johns Hopkins University; University of Maryland; Columbia University; Emory University; University of Southern California; Brigham and Women's Hospital; Weill Medical College of Cornell University; Dartmouth-Hitchcock Medical Center; Ohio State University; University of Virginia; Thomas Jefferson University; Montreal Neurological Institute and Hospital; Minnesota Comprehensive Epilepsy Program
• Investigators: Principal Investigator: Andrew G Herzog, M.D., M.Sc., Beth Israel Deaconess Medical Center

Publications and helpful links

General Publications

• Herzog AG, Klein P, Ransil BJ. Three patterns of catamenial epilepsy. Epilepsia. 1997 Oct;38(10):1082-8. doi: 10.1111/j.1528-1157.1997.tb01197.x.
• Herzog AG. Progesterone therapy in women with complex partial and secondary generalized seizures. Neurology. 1995 Sep;45(9):1660-2. doi: 10.1212/wnl.45.9.1660.
• Herzog AG. Progesterone therapy in women with epilepsy: a 3-year follow-up. Neurology. 1999 Jun 10;52(9):1917-8. doi: 10.1212/wnl.52.9.1917-a. No abstract available.
• 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. doi: 10.1002/ana.20214.
• Maguire MJ, Nevitt SJ. Treatments for seizures in catamenial (menstrual-related) epilepsy. Cochrane Database Syst Rev. 2021 Sep 16;9(9):CD013225. doi: 10.1002/14651858.CD013225.pub3.

Study record dates

Study Major Dates

• Study Start: October 1, 2000
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: January 15, 2002
• First Submitted That Met QC Criteria: January 15, 2002
• First Posted (Estimate): January 16, 2002

Study Record Updates

• Last Update Posted (Actual): June 5, 2017
• Last Update Submitted That Met QC Criteria: June 2, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Epilepsy; Hormone; Progesterone; Seizure; Catamenial
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Progesterone
• Other Study ID Numbers: 2001P001408; CRC (NINDS); NINDS NS39466