Nimodipine to Prevent LH Surge During Ovulation Induction: Blinded Placebo-controlled RCT
| Status: | Completed |
|---|---|
| Conditions: | Women's Studies |
| Therapuetic Areas: | Reproductive |
| Healthy: | No |
| Age Range: | 25 - 40 |
| Updated: | 4/21/2016 |
| Start Date: | September 2012 |
| End Date: | October 2015 |
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
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).
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).
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.
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.
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
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