Epilepsy
Conditions
Keywords
Epilepsy, Seizure, Hormone, Progesterone, Catamenial
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.
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.
Interventions
BIOLOGICALProgesterone Lozenges
200mg Progesterone Lozenges
OTHERMatched Placebo Lozenges
Matched Placebo Lozenges
Sponsors
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
Beth Israel Deaconess Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention 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.
Eligibility
Sex/Gender
FEMALE
Age
13 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Women Who Show a Greater Than 50% Decline in Average Daily Seizure Frequency | 9 years | Percent of women who show a greater than 50% decline in average daily seizure frequency |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Women Who Show a >50% Decline in Average Daily Seizure Frequency for the Most Severe Seizure Type. | 9 years | Percent of women who show a \>50% decline in average daily seizure frequency for the most severe seizure type. |
| 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 | 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 |
| Changes in Serum Progesterone Levels in Subjects at Baseline and After Treatment. | 9 years | Changes in serum progesterone levels in subjects at baseline and after treatment with progesterone or placebo. |
| Change in Serum Levels of Antiepileptic Drugs on Progesterone and Placebo for Subjects With Catamenial and Non-catamenial Epilepsy. | 9 years | — |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Catamenial Epilepsy: Progesterone Lozenges Subjects with catamenial epilepsy received 200 mg progesterone lozenges | 85 |
| Catamenial Epilepsy: Placebo Lozenges Subjects with catamenial epilepsy received matched placebo lozenges | 45 |
| Noncatamenial Epilespy:Progesterone Lozenges Subjects without catamenial epilepsy received 200 mg progesterone lozenges | 105 |
| Noncatamenial Epilespy: Placebo Lozenges Subjects without catamenial epilepsy received matched placebo lozenges | 59 |
| Total | 294 |
Baseline characteristics
| Characteristic | Catamenial Epilepsy: Progesterone Lozenges | Catamenial Epilepsy: Placebo Lozenges | Noncatamenial Epilespy:Progesterone Lozenges | Noncatamenial Epilespy: Placebo Lozenges | Total |
|---|---|---|---|---|---|
| Age, Continuous | 31.4 years STANDARD_DEVIATION 8.68 | 32.31 years STANDARD_DEVIATION 8.5 | 30.71 years STANDARD_DEVIATION 8.16 | 32.42 years STANDARD_DEVIATION 7.87 | 31.71 years STANDARD_DEVIATION 8.3 |
| Sex: Female, Male Female | 85 Participants | 45 Participants | 105 Participants | 59 Participants | 294 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 85 | 0 / 45 | 1 / 105 | 0 / 59 |
| other Total, other adverse events | 37 / 85 | 23 / 45 | 55 / 105 | 27 / 59 |
| serious Total, serious adverse events | 3 / 85 | 1 / 45 | 3 / 105 | 2 / 59 |
Outcome results
Primary
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
Time frame: 9 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Catamenial Epilepsy: Progesterone Lozenges | Percent of Women Who Show a Greater Than 50% Decline in Average Daily Seizure Frequency | 22.8 percentage of participants |
| Catamenial Epilepsy: Placebo Lozenges | Percent of Women Who Show a Greater Than 50% Decline in Average Daily Seizure Frequency | 20.0 percentage of participants |
| Noncatamenial Epilespy:Progesterone Lozenges | Percent of Women Who Show a Greater Than 50% Decline in Average Daily Seizure Frequency | 20.2 percentage of participants |
| Noncatamenial Epilespy: Placebo Lozenges | Percent of Women Who Show a Greater Than 50% Decline in Average Daily Seizure Frequency | 19.2 percentage of participants |
Secondary
Change in Serum Levels of Antiepileptic Drugs on Progesterone and Placebo for Subjects With Catamenial and Non-catamenial Epilepsy.
Time frame: 9 years
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Catamenial Epilepsy: Progesterone Lozenges | Change in Serum Levels of Antiepileptic Drugs on Progesterone and Placebo for Subjects With Catamenial and Non-catamenial Epilepsy. | Levitracetam | 23.2 mcg/mL | Standard Deviation 17.1 |
| Catamenial Epilepsy: Progesterone Lozenges | Change in Serum Levels of Antiepileptic Drugs on Progesterone and Placebo for Subjects With Catamenial and Non-catamenial Epilepsy. | Topirimate | 10.9 mcg/mL | Standard Deviation 6.9 |
| Catamenial Epilepsy: Progesterone Lozenges | Change in Serum Levels of Antiepileptic Drugs on Progesterone and Placebo for Subjects With Catamenial and Non-catamenial Epilepsy. | Lamotrigine | 11.1 mcg/mL | Standard Deviation 8.2 |
| Catamenial Epilepsy: Progesterone Lozenges | Change in Serum Levels of Antiepileptic Drugs on Progesterone and Placebo for Subjects With Catamenial and Non-catamenial Epilepsy. | Phenytoin | 19.7 mcg/mL | Standard Deviation 6.5 |
| Catamenial Epilepsy: Progesterone Lozenges | Change in Serum Levels of Antiepileptic Drugs on Progesterone and Placebo for Subjects With Catamenial and Non-catamenial Epilepsy. | Carbamazepine | 8.9 mcg/mL | Standard Deviation 2.5 |
| Catamenial Epilepsy: Placebo Lozenges | Change in Serum Levels of Antiepileptic Drugs on Progesterone and Placebo for Subjects With Catamenial and Non-catamenial Epilepsy. | Phenytoin | 17.9 mcg/mL | Standard Deviation 3.9 |
| Catamenial Epilepsy: Placebo Lozenges | Change in Serum Levels of Antiepileptic Drugs on Progesterone and Placebo for Subjects With Catamenial and Non-catamenial Epilepsy. | Carbamazepine | 9.6 mcg/mL | Standard Deviation 1.8 |
| Catamenial Epilepsy: Placebo Lozenges | Change in Serum Levels of Antiepileptic Drugs on Progesterone and Placebo for Subjects With Catamenial and Non-catamenial Epilepsy. | Levitracetam | 22.6 mcg/mL | Standard Deviation 12.5 |
| Catamenial Epilepsy: Placebo Lozenges | Change in Serum Levels of Antiepileptic Drugs on Progesterone and Placebo for Subjects With Catamenial and Non-catamenial Epilepsy. | Lamotrigine | 8.4 mcg/mL | Standard Deviation 4.8 |
| Catamenial Epilepsy: Placebo Lozenges | Change in Serum Levels of Antiepileptic Drugs on Progesterone and Placebo for Subjects With Catamenial and Non-catamenial Epilepsy. | Topirimate | 9.3 mcg/mL | Standard Deviation 4.6 |
Secondary
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.
Time frame: 9 years
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Catamenial Epilepsy: Progesterone Lozenges | Changes in Serum Progesterone Levels in Subjects at Baseline and After Treatment. | Baseline | 9.8 ng/ml |
| Catamenial Epilepsy: Progesterone Lozenges | Changes in Serum Progesterone Levels in Subjects at Baseline and After Treatment. | Treatment | 44.4 ng/ml |
| Catamenial Epilepsy: Placebo Lozenges | Changes in Serum Progesterone Levels in Subjects at Baseline and After Treatment. | Treatment | 9.2 ng/ml |
| Catamenial Epilepsy: Placebo Lozenges | Changes in Serum Progesterone Levels in Subjects at Baseline and After Treatment. | Baseline | 9.1 ng/ml |
| Noncatamenial Epilespy:Progesterone Lozenges | Changes in Serum Progesterone Levels in Subjects at Baseline and After Treatment. | Baseline | 10.8 ng/ml |
| Noncatamenial Epilespy:Progesterone Lozenges | Changes in Serum Progesterone Levels in Subjects at Baseline and After Treatment. | Treatment | 49.6 ng/ml |
| Noncatamenial Epilespy: Placebo Lozenges | Changes in Serum Progesterone Levels in Subjects at Baseline and After Treatment. | Baseline | 9.1 ng/ml |
| Noncatamenial Epilespy: Placebo Lozenges | Changes in Serum Progesterone Levels in Subjects at Baseline and After Treatment. | Treatment | 12.0 ng/ml |
Secondary
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
Time frame: 9 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Catamenial Epilepsy: Progesterone Lozenges | 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 | SGMS | 39.39 percentage of participants |
| Catamenial Epilepsy: Progesterone Lozenges | 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 | SPS | 41.12 percentage of participants |
| Catamenial Epilepsy: Progesterone Lozenges | 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 | CPS | 23.68 percentage of participants |
| Catamenial Epilepsy: Placebo Lozenges | 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 | SGMS | 29.41 percentage of participants |
| Catamenial Epilepsy: Placebo Lozenges | 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 | SPS | 41.21 percentage of participants |
| Catamenial Epilepsy: Placebo Lozenges | 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 | CPS | 18.60 percentage of participants |
| Noncatamenial Epilespy:Progesterone Lozenges | 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 | CPS | 21.21 percentage of participants |
| Noncatamenial Epilespy:Progesterone Lozenges | 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 | SGMS | 21.21 percentage of participants |
| Noncatamenial Epilespy:Progesterone Lozenges | 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 | SPS | 42.22 percentage of participants |
| Noncatamenial Epilespy: Placebo Lozenges | 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 | SGMS | 20.83 percentage of participants |
| Noncatamenial Epilespy: Placebo Lozenges | 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 | SPS | 31.82 percentage of participants |
| Noncatamenial Epilespy: Placebo Lozenges | 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 | CPS | 13.73 percentage of participants |
Secondary
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.
Time frame: 9 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Catamenial Epilepsy: Progesterone Lozenges | Percent of Women Who Show a >50% Decline in Average Daily Seizure Frequency for the Most Severe Seizure Type. | 30.4 percentage of participants |
| Catamenial Epilepsy: Placebo Lozenges | Percent of Women Who Show a >50% Decline in Average Daily Seizure Frequency for the Most Severe Seizure Type. | 24.4 percentage of participants |
| Noncatamenial Epilespy:Progesterone Lozenges | Percent of Women Who Show a >50% Decline in Average Daily Seizure Frequency for the Most Severe Seizure Type. | 22.2 percentage of participants |
| Noncatamenial Epilespy: Placebo Lozenges | Percent of Women Who Show a >50% Decline in Average Daily Seizure Frequency for the Most Severe Seizure Type. | 28.8 percentage of participants |