Use of a Calcium Channel Blocker to Prevent Premature Luteinizing Hormone Surges in Infertility Patients (nimodipine)
Nimodipine (Nimotop® Bayer Pharmaceuticals Corporation), unlike other calcium channel blockers is fat soluble and therefore is able to cross the blood-brain barrier1. Gonadotropin releasing hormone (GnRH) neurons are clustered in the hypothalamus and are dependent on calcium flux to release GnRH responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. In a natural menstrual cycle a spontaneous LH surge occurs mid-cycle which triggers ovulation. The investigators hypothesized that nimodipine, by blocking calcium channels, may effectively suppress the release of GnRH and consequently the natural LH surge.
In this prospective double-blinded randomized study the investigators will evaluate the efficacy of nimodipine to inhibit the natural LH surge in women undergoing controlled ovarian stimulation (COS) and intrauterine insemination (IUI). Nimodipine, if successful, may represent an inexpensive oral medication as an alternative to the currently used GnRH agonists or GnRH antagonists in assisted reproductive technologies like IVF.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
|Official Title:||Using Nimodipine, a Calcium Channel Blocker, to Prevent the LH Surge and Ovulation in Women Undergoing Assisted Reproduction|
- Delay of LH surge by at least 2 days [ Time Frame: From cycle day 3 until a spontaneous LH surge detected in the blood or the administration of the hCG trigger shot. Estimated time frame is 14 days. ] [ Designated as safety issue: No ]Nimodipine or placebo will be administered four times daily once the criterion for hCG triggering (one or more follicles at 1.7 cm diameter on ultrasound) is present in women being monitored for IUI.
- Side effect profile of nimodipine or placebo. [ Time Frame: During tablet administration at mid-cycle. ] [ Designated as safety issue: Yes ]Any side effects (especially related to low blood pressure) will be reported by the subjects and recorded by the study investigators during the administration of nimodipine or placebo.
|Study Start Date:||December 2012|
|Estimated Study Completion Date:||July 2015|
|Primary Completion Date:||April 2014 (Final data collection date for primary outcome measure)|
Nimodipine 30 mg tablets will be self-administered by the subjects every 6 hours starting on the day that the ultrasound criterion for hCG triggering is met. The tablets will be taken for two days or until an LH surge is detected, whichever comes first. If no LH surge by 2 days, the hCG trigger (250 micrograms recombinant hCG) will be given followed by intrauterine insemination (IUI)in 40 hours. If the LH surge is detected, hCG will be given immediately and two IUIs will be performed 24 hours apart.
Nimodipine 30 mg tablets will be self-administered by the subjects every 6 hours starting on the day that the ultrasound criterion for hCG triggering is met. The tablets will be taken for two days or until an LH surge is detected, whichever comes first. If no LH surge by 2 days, the hCG trigger (250 micrograms recombinant hCG) will be given followed by intrauterine insemination (IUI)in 40 hours. If the LH surge is detected, hcg will be given immediately and two IUIs will be performed 24 hours apart.
Other Name: Nimotop
Placebo Comparator: Placebo
Same as for nimodipine but an identical placebo will be self-administered.
Identical inactive tablets.
Other Name: placebo tablets
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01551368
|Toronto Centre for Advanced reproductive Technology (TCART)|
|Toronto, Ontario, Canada, M5S2X9|
|Principal Investigator:||Robert F Casper, MD||Toronto Centre for Advanced Reproductive Technology and University of Toronto|