Unexplained InfertilityNIMONCT01672801
Nimodipine to Prevent LH Surge During Ovulation Induction: Blinded Placebo-controlled RCT
A study testing Nimodipine in people with Unexplained Infertility and Polycystic Ovarian Syndrome, run by Boston IVF at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 25 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Unexplained Infertility, Polycystic Ovarian Syndrome, Anovulatory
- What is being tested?
- Nimodipine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2012to Apr 2014
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 40 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 24Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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).
Read the 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.
- Being tested
- Placebo, Nimodipine
- Medical subject headings
- Polycystic Ovary Syndrome, Anovulation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
oral administration
NimodipineDrug
Also called Nimotop
oral administration
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Nimodipine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 7 days
Secondary outcomes (1)
Number of Participants Experiencing Side Effects
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.
Measured: Starting day 0 of intervention to pregnancy test (approximately 15 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2012 (estimated)
- Study startSep 2012
- Primary completionApr 2014
- Study completionApr 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Unexplained InfertilityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston IVF
- Sponsor type
- University, hospital or other
- Collaborators
- Village Fertility Pharmacy
- Responsible party
- Principal investigator, Alan Penzias, Boston IVF
- Investigators
- Alan S Penzias, MD, Principal investigator, Beth Israel Deaconess Medical Center / Boston IVF
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01672801
- Sponsor's protocol ID
- 2012P-000186
- Acronym
- NIMO
- Status last verified
- Aug 2020
- First submitted
- 22 Aug 2012
- Last updated
- 11 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 15350253Krsmanovic 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.
PubMed 1326758Nunez 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.
PubMed 10830284
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01672801
- Acronym / sponsor ID
- NIMO / 2012P-000186
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Boston IVFUniversity, hospital or other
- Collaborators
- Village Fertility Pharmacy
- Study start
- Sep 2012 (actual)
- Primary completion
- Apr 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 27 Aug 2012 (estimated)
- Results
- Posted 11 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboAll 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 |
| Nimodipine | Active comparator | Drug: NimodipineAll 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 |
Who may qualify
- Ages
- 25 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebooral administration | Drug | Placebo |
| NimodipineAlso: Nimotoporal administration | Drug | Nimodipine |
Primary outcome
LH Surge
Time frame: 7 days
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).
1 secondary outcome
Number of Participants Experiencing Side Effects
Time frame: Starting day 0 of intervention to pregnancy test (approximately 15 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15350253Chen 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.
- Background: PubMed 1326758Krsmanovic 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.
- Background: PubMed 10830284Nunez 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.
- Individual participant dataSharing planned: No
Related trials for Unexplained Infertility
Recruiting
Sperm Preparation Prior to Intrauterine Insemination Study
Infertility, Infertility Secondary
Recruiting
Hormone-free Antral Retrieval for Viable Embryo Storage & Transfer
Infertility
Active, not recruitingPhase 3
FRIEND: Fibroids and Unexplained Infertility Treatment With Epigallocatechin Gallate; A Natural CompounD in Green Tea
Leiomyoma, Uterine
Recruiting
Royal Jelly Supplementation in Unexplained Male Infertility
Unexplained Infertility, Male Infertility
Not yet recruitingObservational study
ERA in Young Primary Infertile RIF Patients
Recurrent Implantation Failure
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alan S Penzias, MD principal investigator
Beth Israel Deaconess Medical Center / Boston IVF
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Nimodipine in people with Unexplained Infertility and Polycystic Ovarian Syndrome, run by Boston IVF at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
LH Surge (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01672801, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2020.