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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Village Fertility Pharmacy
Information provided by (Responsible Party):
Alan Penzias, Boston IVF
ClinicalTrials.gov Identifier:
NCT01672801
First received: August 22, 2012
Last updated: March 24, 2014
Last verified: March 2014
  Purpose

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 Intervention
Unexplained Infertility
Polycystic Ovarian Syndrome
Ovulatory Dysfunction (Absence of or Irregular Ovulation With Unknown Cause)
Drug: clomiphene citrate
Drug: Placebo
Drug: Nimodipine

Study Type: Interventional
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 LH Surge in Women Undergoing Controlled Ovarian Stimulation and Intrauterine Insemination: a Double-blinded, Randomized Controlled Study

Resource links provided by NLM:


Further study details as provided by Boston IVF:

Primary Outcome Measures:
  • LH surge [ Time Frame: The presence or absence of an LH surge after start of intervention ] [ Designated as safety issue: No ]
    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:
  • Side effect profile [ Time Frame: Starting day 0 of intervention to pregnancy test (approximately 15 days) ] [ Designated as safety issue: Yes ]
    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:
  • Gonadotropin levels [ Time Frame: Intervention day 0 to ovulation (approximately 1-7 days) ] [ Designated as safety issue: No ]
    Calculated changes in serum LH, FSH, and estradiol levels between patients in nimodipine and placebo arms


Estimated Enrollment: 90
Study Start Date: September 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Medication given will be 8 total doses of placebo orally 4 times a day for 8 total doses in pre-filled liquid containing syringes
Drug: clomiphene citrate
Other Name: Clomid
Drug: Placebo
Active Comparator: Nimodipine
Nimodipine 30mg liquid orally 4 times a day for 8 total doses in pre-filled syringes
Drug: clomiphene citrate
Other Name: Clomid
Drug: Nimodipine
Other Name: Nimotop

  Eligibility

Ages Eligible for Study:   25 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01672801

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

Publications:
Responsible Party: Alan Penzias, Associate Professor of Obstetrics, Gynecology and Reproductive Biology, Boston IVF
ClinicalTrials.gov Identifier: NCT01672801     History of Changes
Other Study ID Numbers: 2012P-000186
Study First Received: August 22, 2012
Last Updated: March 24, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Infertility
Polycystic Ovary Syndrome
Genital Diseases, Male
Genital Diseases, Female
Ovarian Cysts
Cysts
Neoplasms
Ovarian Diseases
Adnexal Diseases
Gonadal Disorders
Endocrine System Diseases
Nimodipine
Calcium Channel Blockers
Clomiphene
Enclomiphene
Zuclomiphene
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Fertility Agents, Female
Fertility Agents

ClinicalTrials.gov processed this record on October 19, 2014