Use of a Calcium Channel Blocker to Prevent Premature Luteinizing Hormone Surges in Infertility Patients

NCT01551368 | Terminated Phase 2

• 1 other identifier: 09-0175-A
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Infertility

Keywords

male factor; intrauterine insemination; LH surge; controlled ovarian stimulation; clomiphene citrate; letrozole; human menopausal gonadotropins

Outcome Measures

Primary Outcomes (1)

• Delay of LH surge by at least 2 days

  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.

  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.

Secondary Outcomes (1)

• Side effect profile of nimodipine or placebo.

  During tablet administration at mid-cycle.

Study Arms (2)

Nimodipine

EXPERIMENTAL

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.

Drug: Nimodipine

Placebo

PLACEBO COMPARATOR

Same as for nimodipine but an identical placebo will be self-administered.

Drug: Placebo

Interventions

Nimodipine DRUG

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.

Also known as: Nimotop

Nimodipine

Placebo DRUG

Identical inactive tablets.

Also known as: placebo tablets

Placebo

Eligibility Criteria

• Age: 25 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age: 25-40 (at time of enrollment)
• Intact Normal Ovaries (Both)
• Early follicular phase (day 2-4) serum FSH level \< 20 mIU/ml
• Diagnosis of infertility with a recommended treatment of ovarian stimulation and IUI

You may not qualify if:

• BMI \> 38 kg/m2
• Early follicular phase (day 2-4) serum FSH level ≥ 20 mIU/ml
• Overstimulated cycle: \>3 mature follicles (≥17 mm)
• Abnormal uterine cavity and /or tubal blockage
• Diagnosis of infertility with a clear indication for IVF
• Severe male factor infertility: Total Motile Sperm Count \< 2x106 post washing

Sponsors & Collaborators

• Mount Sinai Hospital, Canada: lead

Study Sites (1)

Toronto Centre for Advanced reproductive Technology (TCART)

Toronto, Ontario, M5S2X9, Canada

Location

Related Publications (1)

• Fainaru O, Firestone R, Casper RF. Oral nimodipine inhibits the ovarian cycle in mice. Fertil Steril. 2011 Mar 15;95(4):1494-6. doi: 10.1016/j.fertnstert.2010.12.008. Epub 2010 Dec 31.

  PMID: 21195398 BACKGROUND

MeSH Terms

Conditions

Infertility

Interventions

Nimodipine

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nicotinic Acids

Study Officials

• Robert F Casper, MD

  Toronto Centre for Advanced Reproductive Technology and University of Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Obstetrics and Gynecology

Study Record Dates

• First Submitted: December 15, 2011
• First Posted: March 12, 2012
• Study Start: December 1, 2012
• Primary Completion: April 1, 2014
• Study Completion: July 1, 2017
• Last Updated: March 8, 2019

Record last verified: 2019-03

Locations

CA (1)