Nimodipine to Prevent LH Surge During Ovulation Induction: Blinded Placebo-controlled RCT

NCT01672801 | Completed Results DMC

• 1 other identifier: 2012P-000186
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to test the effectiveness of nimodipine in preventing a luteinizing hormone (LH) surge in women undergoing ovulation induction with clomiphene citrate. It is important to prevent the premature LH surge in controlled ovarian stimulation to allow adequate recruitment of follicles, proper maturation of a dominant follicle before ovulation, and effectively time insemination with semen to allow fertilization of a mature egg to occur. The investigators are also conducting this study to determine medication side effect profile (including lightheadedness or dizziness from low blood pressure or rapid heart rate, headache, and nausea), patient treatment compliance, and clinical pregnancy (positive pregnancy test and ultrasound evidence of fetal heart rate). Finally, LH and follicle stimulating hormone (FSH) serum levels will be measured to determine effect of nimodipine on these hormones. As a calcium channel blocker, nimodipine has been shown to block calcium mediated release of gonadotropin releasing hormone in animal and preliminary human studies. The investigators hypothesize that nimodipine, a calcium channel blocker, will prevent or delay the LH surge during controlled ovarian stimulation cycles using clomiphene citrate in subfertile patients undergoing assisted reproduction with intrauterine insemination (IUI).

Conditions

Unexplained Infertility; Polycystic Ovarian Syndrome; Anovulatory

Outcome Measures

Primary Outcomes (1)

• LH Surge

  Compare the change between placebo treated and nimodipine treated patients by the presence or absence of an LH surge on intervention Day 1 and Day 2. LH surge will be determined by serum LH levels at least two times the baseline serum LH (baseline serum LH = (cycle day 3 serum \[LH\] + cycle day 7 serum \[LH\])/2).

  7 days

Secondary Outcomes (1)

• Number of Participants Experiencing Side Effects

  Starting day 0 of intervention to pregnancy test (approximately 15 days)

Other Outcomes (1)

• Gonadotropin Levels

  Intervention day 0 to ovulation (approximately 1-7 days)

Study Arms (2)

Placebo

PLACEBO COMPARATOR

All subjects in both arms will receive Clomid 100 mg tablets by mouth for 5 days prior to receiving either placebo comparator or active comparator. Placebo comparator subjects will receive 8 total doses of liquid placebo orally 4 times a day for 8 total doses in pre-filled liquid placebo containing syringes

Drug: Placebo

Nimodipine

ACTIVE COMPARATOR

All subjects in both arms will receive Clomid 100 mg tablets by mouth for 5 days prior to receiving either placebo comparator or active comparator. Active comparator subjects will receive Nimodipine 30mg liquid orally 4 times a day for 8 total doses in pre-filled syringes

Drug: Nimodipine

Interventions

Placebo DRUG

oral administration

Placebo

Nimodipine DRUG

oral administration

Also known as: Nimotop

Nimodipine

Eligibility Criteria

• Age: 25 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 25-40 years at the time of enrollment
• Both ovaries intact by history and ultrasound assessment
• Early follicular phase (day 2-4) serum FSH level \<20 mIU/mL
• Diagnosis of subfertility with a recommended treatment of COH and IUI
• Providing written informed consent in English

You may not qualify if:

• Body mass index (BMI) \>38 kg/m2
• Early follicular phase (day 2-4) serum FSH level ≥20 mIU/mL
• History of overstimulated cycle defined as \>3 mature follicles of ≥17 mm
• Abnormal uterine cavity and/or tubal disease (as evidenced by sonohysterogram or hysterosalpingogram)
• Diagnosis of infertility with a clear indication for in-vitro fertilization, such as bilateral tubal occlusion
• Severe male factor infertility: Total Motile Sperm Count \< 2x106 post washing (sperm deemed inadequate for IUI preparation)
• Any ovarian or abdominal abnormality that may interfere with adequate TV ultrasound evaluation
• Absence of one or both ovaries
• Any contraindication to being pregnant or carrying a pregnancy to term
• Unexplained gynecological bleeding
• Any medical condition that would jeopardize the patient or the integrity of the data obtained including:
• Prior reaction or side effects from previous calcium channel blocker use
• Any medical condition that may interfere with the absorption, distribution, metabolism or excretion of nimodipine such as hepatic disease, hypertension, seizure, concurrent infection, depression, reflux (see #12 below).
• Mental health status resulting in cognitive or emotional impairment that would preclude study participation
• The concurrent use of any of the following drugs: \[These medications have been shown to effect the availability of the medication or worsen hypotension symptoms\]

Sponsors & Collaborators

• Boston IVF: lead
• Village Fertility Pharmacy: collaborator

Study Sites (1)

Boston IVF

Waltham, Massachusetts, 02451, United States

Location

Related Publications (3)

• Chen EC, Javors MA, Norris C, Siler-Khodr T, Schenken RS, King TS. Dependence of 3',5'-cyclic adenosine monophosphate--stimulated gonadotropin-releasing hormone release on intracellular calcium levels and L-type calcium channels in superfused GT1-7 neurons. J Soc Gynecol Investig. 2004 Sep;11(6):393-8. doi: 10.1016/j.jsgi.2004.02.010.

  PMID: 15350253 BACKGROUND

• Krsmanovic LZ, Stojilkovic SS, Merelli F, Dufour SM, Virmani MA, Catt KJ. Calcium signaling and episodic secretion of gonadotropin-releasing hormone in hypothalamic neurons. Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8462-6. doi: 10.1073/pnas.89.18.8462.

  PMID: 1326758 BACKGROUND

• Nunez L, Villalobos C, Boockfor FR, Frawley LS. The relationship between pulsatile secretion and calcium dynamics in single, living gonadotropin-releasing hormone neurons. Endocrinology. 2000 Jun;141(6):2012-7. doi: 10.1210/endo.141.6.7491.

  PMID: 10830284 BACKGROUND

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Anovulation

Interventions

Nimodipine

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Alan Penzias
• Organization: Boston IVF

apenzias@bostonivf.com

781-434-6500

Study Officials

• Alan S Penzias, MD

  Beth Israel Deaconess Medical Center / Boston IVF

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Obstetrics, Gynecology and Reproductive Biology

Study Record Dates

• First Submitted: August 22, 2012
• First Posted: August 27, 2012
• Study Start: September 1, 2012
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: August 11, 2020
• Results First Posted: August 11, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)