Study of a COX-2 Inhibitor for Prevention of Ovulation

Study Overview
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Brief Summary
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In this study the investigators propose to evaluate a COX-2 inhibitor(meloxicam) to assess its effect on follicular development and find out if this regimen delays or blocks ovulation while maintaining ovarian cyclicity. The investigators intend to administer 15 mg or 30 mg of meloxicam per day for 18 days starting on day 5 after onset of menses during 3 continuous cycles. The 3 treatment cycles will be preceded and followed by control cycles with no treatment. Ovulation or lack there of will be monitored by transvaginal ultrasound examinations (TVUs), estradiol, luteinizing hormone (LH), and progesterone levels in multiple blood samples in each cycle. The investigators will recruit a total of 56 women. Each woman will be randomly assigned to 1 of the 2 dose regimens of meloxicam, with 28 women assigned to each of the 2 dose regimens. Participating women will demonstrate an ovulatory cycle before starting meloxicam treatment and will be protected from pregnancy by prior sterilization.

Detailed Description
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In a recent study, following follicular development by daily ultrasound examinations in 22 women, meloxicam was administered when the dominant follicle reached a diameter of 18 mm (Jesam, Salvatierra et al. 2010). Results from this study indicate that meloxicam 30 mg given for five days in late follicular phase was more effective at delaying follicular rupture than 15 mg. Follicular rupture was delayed more than 48 hours in 11/22 (50%) volunteers in the group treated with 15 mg/day and in 20/22 (91%) volunteers in the group treated with 30 mg/day.

Official Title
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An Exploratory Study of a COX-2 Inhibitor(Meloxicam) for Prevention of Ovulation

Conditions
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Rupture; Graafian Follicle

Intervention / Treatment
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* Drug: Meloxicam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Proven fertility in the past 18- 40 years old Regular menstrual cycles in the past 3 months (24-35 days) Surgically sterilized Non-lactating Hemoglobin of at least 11 g/dl Willing to give informed consent in writing Exclusion Criteria: Allergy to meloxicam, aspirin, or other NSAIDs Currently pregnant or breast feeding History of gastrointestinal problems like stomach ulcer, bleeding or bowel problems History of heart attack, stroke, or blood clot Hemorrhagic or coagulation disorders Known liver and renal disorder History of or signs and symptoms of cancer, hyperprolactinemia, bloody breast discharge, diabetes, or any endocrine disturbance History of asthma, skin or mucosal allergies Hypertension: systolic blood pressure > 135 mm Hg or diastolic blood pressure >85 mmHg History of mental illness including depression or epilepsy Cigarette smoker Habitual user of anti-inflammatory drugs Alcoholism or any drug abuse Use of anticoagulants or steroids

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: meloxicam<br>15 mg versus 30 mg per day P.O for 15 days, during 3 menstrual cycles | Drug: Meloxicam<br>* 15 mg versus 30 mg per day P.O. for 15 days during 3 menstrual cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Test the efficacy of meloxicam in preventing ovulation as measured by ovarian follicular development and delay in rupture when is administered daily for 18 days, starting on the 5th day of the cycle. | To assess follicular outcomes transvaginal ultrasound will be done to all participants during treatment cycles | 3 menstrual cycles treated (3 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of functioning corpus luteum subsequent to unruptured follicles |  | 3 menstrual cycles treated (3 months) | 
| Bleeding pattern during treatment with meloxicam |  | 3 menstrual cycles treated (3 months) | 
| Incidence of adverse events | In all cycles adverse events will be evaluated with a questionnaire performed in all visits | 3 menstrual cycles treated (3 months) | 
| Pharmacokinetics of meloxicam | During the first treatment cycle, plasma levels of meloxicam will be measured in all participants to evaluate levels obtained with the administration of the drug for 15 consecutive days. Levels of the drug will be correlate with follicular outcomes | 1 menstrual cycle (1 month) | 
| Levels of estradiol |  | 3 menstrual cycles treated (3 months) | 
| Levels of progesterone |  | 3 menstrual cycles (3 months) | 
| Levels of LH |  | 3 menstrual cycles (3 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ovulation, unruptured luteinized follicle, meloxicam