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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01672801
Recruitment Status : Completed
First Posted : August 27, 2012
Last Update Posted : January 12, 2016
Village Fertility Pharmacy
Information provided by (Responsible Party):
Alan Penzias, Boston IVF

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).

Condition or disease Intervention/treatment Phase
Unexplained Infertility Polycystic Ovarian Syndrome Anovulatory Drug: Placebo Drug: Nimodipine Not Applicable

Detailed Description:

After enrollment, subjects will be randomized to Placebo Comparator or Active Comparator. All subjects will receive Clomid 100 mg for 5 days for the purpose of ovarian follicle recruitment. Intervention will be initiated once ovarian follicle maturation has been documented (≥1 ovarian follicle size of ≥ 17mm) and the absence of a premature LH surge has been confirmed - this will be classified as intervention day 0. Subjects will receive their assigned comparator (Placebo or Active) according the schedule below:

  • Intervention Day 0 - noon / afternoon / bedtime (3 doses)
  • Intervention Day 1 - morning / noon / afternoon / bedtime (4 doses)
  • Intervention Day 2 - morning (1 dose) Serum hormone levels and ultrasound examination will occur on days 0,1 and 2 for all subjects.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Using Nimodipine, a Calcium Channel Blocker, to Prevent LH Surge in Women Undergoing Controlled Ovarian Stimulation and Intrauterine Insemination: a Double-blinded, Randomized Controlled Study
Study Start Date : September 2012
Actual Primary Completion Date : April 2014
Actual Study Completion Date : October 2015

Resource links provided by the National Library of Medicine

Drug Information available for: Nimodipine

Arm Intervention/treatment
Placebo Comparator: Placebo
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
oral administration

Active Comparator: Nimodipine
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
oral administration
Other Name: Nimotop

Primary Outcome Measures :
  1. LH surge [ Time Frame: The presence or absence of an LH surge after start of intervention ]
    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).

Secondary Outcome Measures :
  1. Side effect profile [ Time Frame: Starting day 0 of intervention to pregnancy test (approximately 15 days) ]
    Medication side effect profile including: symptomatic hypotension (Note: vital signs will be recorded), symptomatic tachycardia (Note: vital signs will be recorded), headache, nausea. These will be self-reported with constructed questionnaire.

Other Outcome Measures:
  1. Gonadotropin levels [ Time Frame: Intervention day 0 to ovulation (approximately 1-7 days) ]
    Calculated changes in serum LH, FSH, and estradiol levels between patients in nimodipine and placebo arms

Information from the National Library of Medicine

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Ages Eligible for Study:   25 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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]
  • Antihypertensives (eg. ACE inhibitors, alpha-adrenergic blocking agents,methyldopa, beta-blockers, diuretics, PDE5 inhibitors, and other calcium antagonists)
  • Antiepileptics (eg. phenobarbital, phenytoin, carbamazepine or valproic acid)
  • Macrolide antibiotics (eg, erythromycin)
  • Azole antimycotics (eg, ketoconazole)
  • HIV protease inhibitors (eg, ritonavir)
  • Antidepressants (eg, nefazodone and fluoxetine)
  • Cimetidine
  • Patient unable to communicate adequately with the investigators and to comply with the requirements of the study
  • Unwillingness to give written informed consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01672801

United States, Massachusetts
Boston IVF
Waltham, Massachusetts, United States, 02451
Sponsors and Collaborators
Boston IVF
Village Fertility Pharmacy
Principal Investigator: Alan S Penzias, MD Beth Israel Deaconess Medical Center / Boston IVF

Publications of Results:
Responsible Party: Alan Penzias, Associate Professor of Obstetrics, Gynecology and Reproductive Biology, Boston IVF Identifier: NCT01672801     History of Changes
Other Study ID Numbers: 2012P-000186
First Posted: August 27, 2012    Key Record Dates
Last Update Posted: January 12, 2016
Last Verified: July 2015

Additional relevant MeSH terms:
Polycystic Ovary Syndrome
Genital Diseases, Male
Genital Diseases, Female
Ovarian Cysts
Ovarian Diseases
Adnexal Diseases
Gonadal Disorders
Endocrine System Diseases
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Vasodilator Agents