Clinical trial NCT01346137: Study of a COX-2 Inhibitor for Prevention of Ovulation
Official title: An Exploratory Study of a COX-2 Inhibitor(Meloxicam) for Prevention of Ovulation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Rupture; Graafian Follicle
Keywords: ovulation
unruptured luteinized follicle
meloxicam
Lead sponsor: Instituto Chileno de Medicina Reproductiva
Sponsor class: OTHER
Collaborators: name: CONRAD
First posted: 2011-05-02
Enrollment: 56
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 3 menstrual cycles treated (3 months)
Secondary outcomes:
measure: Occurrence of functioning corpus luteum subsequent to unruptured follicles
timeFrame: 3 menstrual cycles treated (3 months)
measure: Bleeding pattern during treatment with meloxicam
timeFrame: 3 menstrual cycles treated (3 months)
measure: Incidence of adverse events
timeFrame: 3 menstrual cycles treated (3 months)
measure: Pharmacokinetics of meloxicam
timeFrame: 1 menstrual cycle (1 month)
measure: Levels of estradiol
timeFrame: 3 menstrual cycles treated (3 months)
measure: Levels of progesterone
timeFrame: 3 menstrual cycles (3 months)
measure: Levels of LH
timeFrame: 3 menstrual cycles (3 months)
Other outcomes:
Locations:
city: Santiago
country: Chile
facility: Instituto Chileno de Medicina Reproductiva (ICMER)
Study officials:
affiliation: Instituto Chileno de Medicina Reproductiva
name: Cristián Jesam, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jesam C, Salvatierra AM, Schwartz JL, Croxatto HB. Suppression of follicular rupture with meloxicam, a cyclooxygenase-2 inhibitor: potential for emergency contraception. Hum Reprod. 2010 Feb;25(2):368-73. doi: 10.1093/humrep/dep392. Epub 2009 Nov 19.
citation: Bata MS, Al-Ramahi M, Salhab AS, Gharaibeh MN, Schwartz J. Delay of ovulation by meloxicam in healthy cycling volunteers: A placebo-controlled, double-blind, crossover study. J Clin Pharmacol. 2006 Aug;46(8):925-32. doi: 10.1177/0091270006289483.
citation: Jesam C, Salvatierra AM, Schwartz JL, Fuentes A, Croxatto HB. Effect of oral administration of a continuous 18 day regimen of meloxicam on ovulation: experience of a randomized controlled trial. Contraception. 2014 Aug;90(2):168-73. doi: 10.1016/j.contraception.2014.04.011. Epub 2014 May 5.