Obesity
Conditions
Keywords
Obesity, Body weight, Emergency contraception, Levonogestrel, Ulipristal acetate
Brief summary
Obese women are significantly more likely than their normal BMI counterparts to experience failure of orally-dosed emergency contraceptives. The PI's preliminary data provides evidence for testing a dose escalation strategy in an effort to provide improved efficacy from orally-dosed emergency contraceptives in obese women. The overall project will be focused on both levonorgestrel (LNG) - and ulipristal acetate-containing emergency contraception but this protocol registration is for the LNG aspect of the study procedures.
Detailed description
Emergency contraception (EC) provides a woman with an additional line of defense against unintended pregnancy following an act of unprotected intercourse. Orally-dosed EC works by delaying ovulation and reduces the risk of pregnancy for a single act of unprotected intercourse by 50-70%. Unfortunately, obese women are significantly more likely than their normal BMI counterparts to experience failure of orally-dosed EC and in some instances EC is equivalent to placebo. The PI's preliminary data provides evidence for testing a dose escalation strategy in an effort to provide improved efficacy from orally-dosed EC in obese women. The hypothesis is that increasing the dose of orally-dosed EC agents will normalize the pharmacokinetics resulting in the expected treatment effect (delay in follicle rupture) in obese women. In the overall proposal, the investigators plan to perform detailed pharmacokinetic and pharmacodynamic studies of ulipristal acetate-based EC in obese women and expand upon the preliminary findings of levonorgestrel-based EC. This protocol registration is for the LNG aspect of the study procedures focused on the pharmacodynamics of LNG dose escalation
Interventions
DRUGLevonorgestrel-based emergency contraception 1.5 mg
Evaluating pharmacodynamic outcomes in obese women using 1.5mg versus 3.0mg of LNG-based EC
DRUGLevonorgestrel-based emergency contraception 3.0mg
Evaluating pharmacodynamic outcomes in obese women using 1.5mg versus 3.0mg of LNG-based EC
Sponsors
National Institutes of Health (NIH)
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Generally health women * Aged 18-35 years old * Regular menses (every 21-35 days) experiencing an ovulatory screening cycle with a progesterone level of 3ng/ml or greater. * Subjects must have a BMI of \>30 kg/m2 and weigh at least 80 kg or more.
Exclusion criteria
* Metabolic disorders including uncontrolled thyroid dysfunction and Polycystic Ovarian Syndrome * Impaired liver or renal function * Actively seeking or involved in a weight loss program (must be weight stable) pregnancy, breastfeeding, or seeking pregnancy * Recent (within last 8 weeks) use of hormonal contraception * Current use of drugs that interfere with metabolism of sex steroids * Smokers.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants in Two Treatment Groups (1.5mg Levonorgestrel and 3mg Levonorgestrel) With no Follicle Rupture at 5 Days Within One Menstrual (Treatment) Cycle. | 5 days post-LNG dosing | No evidence of follicle rupture achieved by participant in one menstrual (treatment) cycle at 5 days post LNG dosing. Follicle rupture is defined as the disappearance of or \>50% reduction in the size of the leading follicle. Dosing occurred after a dominant follicle measuring 15 mm or greater in at least one dimension was visualized on ultrasound. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Follicle Rupture Before 5 Days | 5 days | Among the participants with follicle rupture before 5 days, the time to rupture was measured and reported for each day up to day 5. If the date of follicle rupture was unclear by ultrasonographic imaging (eg, collapse was seen, but reduction of size was less than 50%), serum hormone levels were used to adjudicate day of ruptures. |
Countries
United States
Participant flow
Recruitment details
Recruitment took place at Oregon Health & Science University and Eastern Virginia Medical School from June 2017 to February 2021. The study recruited healthy individuals aged 18-35 years with regular menstrual cycles (21-35 days) and BMIs higher than 30 with weights of 176 pounds or more.
Pre-assignment details
After enrollment, participants started their treatment cycle at the time of next menses or could delay for 1-2 menstrual cycles if a scheduling conflict occurred. On days 6-8 of the treatment cycle, participants were monitored every other day for follicular activity with transvaginal ultrasonographic examination, as well as blood sampling for progesterone, estradiol, and LH until a dominant follicle measuring 15 mm or greater in at least one dimension was visualized.
Participants by arm
| Arm | Count |
|---|---|
| LNG-ECx1 Levonorgestrel 1.5 mg orally x 1 dose. Timing of dosage depends on ovarian follicle measurements.
Levonorgestrel-based emergency contraception 1.5 mg: Evaluating pharmacodynamic outcomes in obese women using 1.5mg versus 3.0mg of LNG-based EC | 35 |
| LNG-ECx2 Levonorgestrel 3mg orally x 1 dose. Timing of dosage depends on ovarian follicle measurements.
Levonorgestrel-based emergency contraception 3.0mg: Evaluating pharmacodynamic outcomes in obese women using 1.5mg versus 3.0mg of LNG-based EC | 35 |
| Total | 70 |
Baseline characteristics
| Characteristic | LNG-ECx2 | Total | LNG-ECx1 |
|---|---|---|---|
| Age, Continuous | 29.3 years STANDARD_DEVIATION 4.4 | 28.7 years STANDARD_DEVIATION 4 | 28.2 years STANDARD_DEVIATION 3.5 |
| BMI | 38.8 kg/m^2 STANDARD_DEVIATION 5.8 | 38.0 kg/m^2 STANDARD_DEVIATION 5.6 | 37.3 kg/m^2 STANDARD_DEVIATION 5.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 12 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants | 58 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Nulligravid | 19 Participants | 35 Participants | 16 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 10 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 27 Participants | 54 Participants | 27 Participants |
| Region of Enrollment United States | 35 participants | 70 participants | 35 participants |
| Sex: Female, Male Female | 35 Participants | 70 Participants | 35 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Weight (lbs) | 236.4 pounds STANDARD_DEVIATION 39.1 | 230.7 pounds STANDARD_DEVIATION 36.5 | 224.9 pounds STANDARD_DEVIATION 33.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 35 |
| other Total, other adverse events | 13 / 35 | 14 / 35 |
| serious Total, serious adverse events | 0 / 35 | 0 / 35 |
Outcome results
Primary
The Number of Participants in Two Treatment Groups (1.5mg Levonorgestrel and 3mg Levonorgestrel) With no Follicle Rupture at 5 Days Within One Menstrual (Treatment) Cycle.
No evidence of follicle rupture achieved by participant in one menstrual (treatment) cycle at 5 days post LNG dosing. Follicle rupture is defined as the disappearance of or \>50% reduction in the size of the leading follicle. Dosing occurred after a dominant follicle measuring 15 mm or greater in at least one dimension was visualized on ultrasound.
Time frame: 5 days post-LNG dosing
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LNG-ECx1 | The Number of Participants in Two Treatment Groups (1.5mg Levonorgestrel and 3mg Levonorgestrel) With no Follicle Rupture at 5 Days Within One Menstrual (Treatment) Cycle. | 18 participants |
| LNG-ECx2 | The Number of Participants in Two Treatment Groups (1.5mg Levonorgestrel and 3mg Levonorgestrel) With no Follicle Rupture at 5 Days Within One Menstrual (Treatment) Cycle. | 24 participants |
Secondary
Number of Participants With Follicle Rupture Before 5 Days
Among the participants with follicle rupture before 5 days, the time to rupture was measured and reported for each day up to day 5. If the date of follicle rupture was unclear by ultrasonographic imaging (eg, collapse was seen, but reduction of size was less than 50%), serum hormone levels were used to adjudicate day of ruptures.
Time frame: 5 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LNG-ECx1 | Number of Participants With Follicle Rupture Before 5 Days | 17 Participants |
| LNG-ECx2 | Number of Participants With Follicle Rupture Before 5 Days | 11 Participants |