EpilepsyPhase 3NCT00029536
Progesterone vs Placebo Therapy for Women With Epilepsy
A Phase 3 study testing Progesterone Lozenges in people with Epilepsy, run by Beth Israel Deaconess Medical Center at 15 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 13 to 45 years, women only
- Conditions the study is for
- Epilepsy
- What is being tested?
- Progesterone Lozenges
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 294 participants
- Where
- 15 sitesin 2 countries
- Study dates
- Oct 2000to Jun 2010
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 to 45 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
15 sites in 2 countries.
15 sites in 2 countries
United States14 sites
Emory University School of Medicine
Atlanta, Georgia, 30322
University of Maryland
Baltimore, Maryland, 21201
Johns Hopkins Bayview Medical Center; Johns Hopkins Hospital
Baltimore, Maryland, 21287
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Beth Israel Deaconess Medical Center, Harvard Neuroendocrine Unit
Boston, Massachusetts, 02215
University of Virginia
Charlottesville, Virginia, 22908
Ohio State University
Columbus, Ohio, 43210
Henry Ford Hospital
Detroit, Michigan, 48202
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756
University of Southern California, Keck School of Medicine
Los Angeles, California, 90033
MINCEP Epilepsy Care
Minneapolis, Minnesota, 55416
New York Presbyterian Hospital- Weill Medical College of Cornell University, Comprehensive Epilepsy Center
New York, New York, 10021
Columbia Medical Center
New York, New York, 10032
Thomas Jefferson University Hospital, Comprehensive Epilepsy Center
Philadelphia, Pennsylvania, 19107
About this study
Official title: 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.
Read the 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.
- Conditions
- Epilepsy
- Being tested
- Progesterone Lozenges, Matched Placebo Lozenges
- Keywords
- Epilepsy, Seizure, Hormone, Progesterone, Catamenial
- Medical subject headings
- Epilepsy, Seizures
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Progesterone LozengesBiological
200mg Progesterone Lozenges
Matched Placebo LozengesOther
Matched Placebo Lozenges
| Study group | Role | What they receive |
|---|---|---|
| Catamenial Epilepsy: Progesterone Lozenges | Experimental | Subjects with catamenial epilepsy received 200 mg progesterone lozenges Receives: Biological: Progesterone Lozenges |
| Catamenial Epilepsy: Placebo Lozenges | Placebo comparator | Subjects with catamenial epilepsy received matched placebo lozenges Receives: Other: Matched Placebo Lozenges |
| Noncatamenial Epilespy:Progesterone Lozenges | Experimental | Subjects without catamenial epilepsy received 200 mg progesterone lozenges Receives: Biological: Progesterone Lozenges |
| Noncatamenial Epilespy: Placebo Lozenges | Placebo comparator | Subjects without catamenial epilepsy received matched placebo lozenges Receives: Other: Matched Placebo Lozenges |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 9 years
Secondary outcomes (4)
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.
Measured: 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
Measured: 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.
Measured: 9 years
Change in Serum Levels of Antiepileptic Drugs on Progesterone and Placebo for Subjects With Catamenial and Non-catamenial Epilepsy.
Measured: 9 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2002 (estimated)
- Study startOct 2000
- Primary completionJun 2010
- Study completionJun 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for EpilepsyStudies of the same condition, open and under way.
- More trials run by Beth Israel Deaconess Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 294 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beth Israel Deaconess Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Brigham and Women's Hospital, Columbia University, Dartmouth-Hitchcock Medical Center, Emory University, Johns Hopkins University, 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, Minnesota Comprehensive Epilepsy Program
- Responsible party
- Principal investigator, Andrew Herzog, Beth Israel Deaconess Medical Center
- Investigators
- Andrew G Herzog, M.D., M.Sc., Principal investigator, Beth Israel Deaconess Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00029536
- Sponsor's protocol ID
- 2001P001408
- Other IDs
- NINDS NS39466, CRC
- Status last verified
- Jun 2017
- First submitted
- 15 Jan 2002
- Last updated
- 5 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 7675223Herzog 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.
PubMed 10371551Herzog 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.
PubMed 9579954Herzog 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.
PubMed 15349872Maguire 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.
PubMed 34528245
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 3 Study of Progesterone vs Placebo Therapy
- ClinicalTrials.gov ID
- NCT00029536
- Acronym / sponsor ID
- 2001P001408
- Conditions
- Epilepsy
- Keywords
- Epilepsy, Seizure, Hormone, Progesterone, Catamenial
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 294 participants (actual)
- Lead sponsor
- Beth Israel Deaconess Medical CenterUniversity, hospital or other
- Collaborators
- Brigham and Women's Hospital, Columbia University, Dartmouth-Hitchcock Medical Center, Emory University, Johns Hopkins University, 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, Minnesota Comprehensive Epilepsy Program
- Study start
- Oct 2000
- Primary completion
- Jun 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 16 Jan 2002 (estimated)
- Results
- Posted 5 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Catamenial Epilepsy: Progesterone Lozenges | Experimental | Biological: Progesterone LozengesSubjects with catamenial epilepsy received 200 mg progesterone lozenges |
| Catamenial Epilepsy: Placebo Lozenges | Placebo comparator | Other: Matched Placebo LozengesSubjects with catamenial epilepsy received matched placebo lozenges |
| Noncatamenial Epilespy:Progesterone Lozenges | Experimental | Biological: Progesterone LozengesSubjects without catamenial epilepsy received 200 mg progesterone lozenges |
| Noncatamenial Epilespy: Placebo Lozenges | Placebo comparator | Other: Matched Placebo LozengesSubjects without catamenial epilepsy received matched placebo lozenges |
Who may qualify
- Ages
- 13 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Progesterone Lozenges200mg Progesterone Lozenges | Biological | Catamenial Epilepsy: Progesterone Lozenges, Noncatamenial Epilespy:Progesterone Lozenges |
| Matched Placebo LozengesMatched Placebo Lozenges | Other | Catamenial Epilepsy: Placebo Lozenges, Noncatamenial Epilespy: Placebo Lozenges |
Primary outcome
Percent of Women Who Show a Greater Than 50% Decline in Average Daily Seizure Frequency
Time frame: 9 years
Percent of women who show a greater than 50% decline in average daily seizure frequency
4 secondary outcomes
Percent of Women Who Show a >50% Decline in Average Daily Seizure Frequency for the Most Severe Seizure Type.
Time frame: 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
Time frame: 9 years
Changes in Serum Progesterone Levels in Subjects at Baseline and After Treatment.
Time frame: 9 years
Change in Serum Levels of Antiepileptic Drugs on Progesterone and Placebo for Subjects With Catamenial and Non-catamenial Epilepsy.
Time frame: 9 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 7675223Herzog 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.
- Background: PubMed 10371551Herzog 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.
- Background: PubMed 9579954Herzog 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.
- Results publication: PubMed 15349872Herzog 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.
- Derived from this study: PubMed 34528245Maguire 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew G Herzog, M.D., M.Sc. principal investigator
Beth Israel Deaconess Medical Center
15 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Progesterone Lozenges in people with Epilepsy, run by Beth Israel Deaconess Medical Center at 15 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent of Women Who Show a Greater Than 50% Decline in Average Daily Seizure Frequency (time frame: 9 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00029536, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2017.