Progesterone vs Placebo Therapy for Women With Epilepsy

NCT00029536 | Completed Phase 3 Results DMC

• 3 other identifiers: 2001P001408NINDS NS39466CRC
• Study Type: interventional
• Target: 294
• Locations: 2 countries
• Sites: 15

Brief Summary

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.

Conditions

Epilepsy

Keywords

Epilepsy; Seizure; Hormone; Progesterone; Catamenial

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

  9 years

• Changes in Serum Progesterone Levels in Subjects at Baseline and After Treatment.

  9 years

• Change in Serum Levels of Antiepileptic Drugs on Progesterone and Placebo for Subjects With Catamenial and Non-catamenial Epilepsy.

  9 years

Study Arms (4)

Catamenial Epilepsy: Progesterone Lozenges

EXPERIMENTAL

Subjects with catamenial epilepsy received 200 mg progesterone lozenges

Biological: Progesterone Lozenges

Catamenial Epilepsy: Placebo Lozenges

PLACEBO COMPARATOR

Subjects with catamenial epilepsy received matched placebo lozenges

Other: Matched Placebo Lozenges

Noncatamenial Epilespy:Progesterone Lozenges

EXPERIMENTAL

Subjects without catamenial epilepsy received 200 mg progesterone lozenges

Biological: Progesterone Lozenges

Noncatamenial Epilespy: Placebo Lozenges

PLACEBO COMPARATOR

Subjects without catamenial epilepsy received matched placebo lozenges

Other: Matched Placebo Lozenges

Interventions

Progesterone Lozenges BIOLOGICAL

200mg Progesterone Lozenges

Catamenial Epilepsy: Progesterone Lozenges; Noncatamenial Epilespy:Progesterone Lozenges

Matched Placebo Lozenges OTHER

Matched Placebo Lozenges

Catamenial Epilepsy: Placebo Lozenges; Noncatamenial Epilespy: Placebo Lozenges

Eligibility Criteria

• Age: 13 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

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

You may not qualify if:

• Subject that is pregnant or lactating.
• Subject that is on major tranquilizers, antidepressant medications, or reproductive hormones.
• Subject that is unable to document seizures.
• Subject that has progressive neurological or systemic disorder or \> 2-fold elevation in liver enzyme levels

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• Brigham and Women's Hospital: collaborator
• Columbia University: collaborator
• Dartmouth-Hitchcock Medical Center: collaborator
• Emory University: collaborator
• Johns Hopkins University: collaborator
• Montreal Neurological Institute and Hospital: collaborator
• Ohio State University: collaborator
• Thomas Jefferson University: collaborator
• University of Maryland: collaborator
• University of Southern California: collaborator
• University of Virginia: collaborator
• Weill Medical College of Cornell University: collaborator
• Minnesota Comprehensive Epilepsy Program: collaborator

Study Sites (15)

University of Southern California, Keck School of Medicine

Los Angeles, California, 90033, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins Bayview Medical Center; Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center, Harvard Neuroendocrine Unit

Boston, Massachusetts, 02215, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

MINCEP Epilepsy Care

Minneapolis, Minnesota, 55416, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

New York Presbyterian Hospital- Weill Medical College of Cornell University, Comprehensive Epilepsy Center

New York, New York, 10021, United States

Location

Columbia Medical Center

New York, New York, 10032, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Thomas Jefferson University Hospital, Comprehensive Epilepsy Center

Philadelphia, Pennsylvania, 19107, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Montreal Neurological Institute

Montreal, Quebec, H3A 2B4, Canada

Location

Related Publications (5)

• 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.

  PMID: 7675223 BACKGROUND

• 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.

  PMID: 10371551 BACKGROUND

• 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.

  PMID: 9579954 BACKGROUND

• 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.

  PMID: 15349872 RESULT

• 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.

  PMID: 34528245 DERIVED

MeSH Terms

Conditions

Epilepsy; Seizures

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Andrew G. Herzog
• Organization: Beth Israel Deaconess Medical Center

aherzog@bidmc.harvard.edu

781-431-0277

Study Officials

• Andrew G Herzog, M.D., M.Sc.

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology

Model Details: This was a phase III, randomized, double-blind, placebo-controlled, multicenter trial. Randomization was carried out separately for women with and without catamenial epilepsy, 2:1 to progesterone or placebo.

Study Record Dates

• First Submitted: January 15, 2002
• First Posted: January 16, 2002
• Study Start: October 1, 2000
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: June 5, 2017
• Results First Posted: June 5, 2017

Record last verified: 2017-06

Locations

CA (1); US (14)