Frozen Embryo TransferPhase 2AMLODIPNCT04954196
Benefit of Amlodipine in HRT Cycle for Frozen Embryo Transfer in the Correction of Uterine Pulsatility Index
A Phase 2 study testing Amlodipine 5mg in people with Frozen Embryo Transfer, run by University Hospital, Montpellier.
Trial summary
Embryo implantation depends on two main factors: embryo grading quality and endometrial receptivity.Numerous tools have been suggested to evaluate these two factors. Measurement of the pulsatility index (PI) of the uterine arteries is associated with extremely low chances of pregnancy when it is high, especially… Read more about this study
- Who is it for?
- Ages 18 to 38 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Frozen Embryo Transfer
- What is being tested?
- Amlodipine 5mg
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 8 Oct 2021to 8 Sep 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 18 to 38 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Female subject
- 18 years (≤) age (≤) 38 years
- Patient scheduled for a blastocyst frozen transfer (vitrification on Day 5) on HRT cycle (hormone replacement therapy)
- Measurement of at least one of the two uterine PI (pulsatility index) greater than 3 (> 3) at the first monitoring Dm (corresponding to Day 13-Day 16 of the cycle)
- BMI ≤ 30 kg / m2
- Carrying out a transfer test qualified as easy (passage through the cervix of a flexible or rigid catheter, without anesthesia or Pozzi forceps)
- Collection and signature of free and informed consent
- Subject affiliated to or beneficiary of a health insurance plan
Who cannot join
- Active smoker patient (at least one cigarette a day at the enrollment in the study)
- Oocyte recipient patient
- A pre-implantation genetic screening (PGS) is planned for the patient
- Patient with stage 3 or 4 endometriosis, or adenomyosis
- Contraindication to the use of amlodipine (recent myocardial infarction less than one month old, severe angina pectoris, severe hepatic insufficiency, treatment with ciclosporin, hypotension, hypersensitivity to amlodipine, dihydropyridine derivatives)
- Concomitant use of inhibitors or enzyme inducers of CYP3A4
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- Patient already being treated for high blood pressure
- Patient with an ovarian follicle recruitmant (> 12mm) during the first monitoring (the most conservative case)
- Patient participating in another human intervention study
- Patient in the exclusion period determined by a previous study
- Patient has already participated in this study
- Patient under legal protection, guardianship or curatorship
- Impossibility to give the patient clarifying information
- Impossibility to perform monitoring by an experienced sonographer
- Breastfeeding patient according to article L1121-5 of the CSP
- Patient protected or unable to give consent according to article L1121-8 of the Public Health Code (CSP)
- Vulnerable person according to article L1121-6 of the CSP
About this study
Official title: Benefit of Amlodipine in HRT Cycle (Hormone Replacement Therapy) for Frozen Embryo Transfer in the Correction of Uterine Pulsatility Index: Randomized Controlled Double-blind Trial.
Embryo implantation depends on two main factors: embryo grading quality and endometrial receptivity.Numerous tools have been suggested to evaluate these two factors. Measurement of the pulsatility index (PI) of the uterine arteries is associated with extremely low chances of pregnancy when it is high, especially higher than 3.
A pilot study of women with premature ovarian failure with at least one of the uterine PIs greater than 3 showed the efficiency of nifedipine in uterine vascularization. This calcium channel blocker, used sublingually in this study, significantly lowered uterine PI in nearly half an hour.
We are therefore interested in exploring this accessible, non-invasive and inexpensive tool, in the evaluation of endometrial receptivity before an embryo transfer.
Read the detailed description
Embryo implantation is a key stage that depends on two main factors: embryo grading quality and endometrial receptivity. Numerous tools have been suggested to evaluate these two factors, without making it possible to predict with certainty the outcome of an embryo transfer in terms of pregnancy. However, some diagnostic tests have shown a good negative predictive value: it is the case of the measurement of the pulsatility index (PI) of the uterine arteries which is associated with extremely low chances of pregnancy when it is high, especially higher than 3 (Cacciatore et al., 1996; Steer et al., 1992).
The Pulsatility Index PI is calculated by the ratio between the maximum amplitude of the tracing and the mean velocity. It evolves according to downstream resistance. Uterine hypoperfusion would readily be associated with subfertility (Goswamy et al., 1988). The uterine arterial pulsatility index is easily accessible during pelvic ultrasound, with satisfactory intra- and inter-observer reproducibility (Steer et al., 1995). There is no significant difference between the measurement of the right and left uterine PI (Favre et al., 1993). Uterine PIs vary during the menstrual cycle (Goswamy and Steptoe, 1988) and depending on hormonal effects (de Ziegler et al., 1991; Strigini et al., 1995) or ovarian micropolycystic status (PCOS, syndrome of polycystic ovaries) of the patient (Resende et al., 2001). The impact of tobacco (Battaglia et al., 2011) and parity (Guedes-Martins et al., 2015) on uterine PIs is described in the literature. Age, although controversial, does not seem to have an impact on uterine PIs, at least in premenopausal women case (Check et al., 2000). Likewise, body mass index (BMI) could have an impact on PIs, as in increased PIs in obese women (Battaglia et al., 1996; Zeng et al., 2013) If high uterine PIs are associated with reduced chances of pregnancy, how can they be improved? A pilot study of women with premature ovarian failure with uterine PIs greater than 3 showed the efficiency of nifedipine in uterine vascularization. This calcium channel blocker, used sublingually in this study, significantly lowered uterine PI in nearly half an hour (Huissoud et al., 2004). This medication could therefore be promising in the treatment of patients in assisted medical reproduction (ART) for whom the measurements of the uterine PIs would be greater than 3 and therefore have lower chances of pregnancy.
This study aims to investigate weither the use of a calcium channel blocker (amlodipine) improves the value of uterine PIs in patients with at least one of the uterine PIs greater than 3, during a cycle for frozen embryo transfer (FET).
- Conditions
- Frozen Embryo Transfer
- Being tested
- Amlodipine 5mg, Placebo
- Keywords
- Frozen embryo transfer, Uterine artery pulsatility index, Implantation, Calcium channel blocker
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Amlodipine 5mgDrug
Also called AMLODIPINE ARROW GÉNÉRIQUES 5 mg
HRT administration: On Day 1 of the cycle, HRT is planned in accordance with the department's standard practice.
- The frozen embryo transfer will be performed 6 days after progesterone initiation.
- The HRT will be maintained until the pregnancy test is performed: If the test is positive,HRT will be continued for up to 12 weeks of amenorrhea at the same doses and then gradually stopped. If the test is negative,HRT will be stopped gradually
Amlodipine administration: On the day of the first monitoring Dm (corresponding to D13 D16 of the cycle), a single per os dose of amlodipine 5 mg is taken at night, neither the patient nor the investigator knows what drug is the patient getting. Monitoring is systematically performed the next morning.The treatment will be maintained until the pregnancy test is performed then if the test is positive, the treatment will be maintained for a total duration of 7 weeks.
PlaceboDrug
HRT administration: On Day 1 of the cycle, HRT is planned in accordance with the department's standard practice.
- The frozen embryo transfer will be performed 6 days after progesterone initiation.
- The HRT will be maintained until the pregnancy test is performed: If the test is positive, HRT will be continued for up to 12 weeks of amenorrhea at the same doses and then gradually stopped. If the test is negative, HRT will be stopped gradually
Placebo administration:On the day of the first monitoring Dm (corresponding to D13-D16 of the cycle), a single per os dose of placebo (Microcrystalline cellulose) is taken at night, neither the patient nor the investigator knows what drug is the patient getting. Monitoring is systematically performed the next morning.. The treatment will be maintained until the pregnancy test is performed, then if the test is positive, the treatment will be maintained for a total duration of 7 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Amlodipine arm | Experimental | Single dose per os Amlodipine 5mg administration per day Receives: Drug: Amlodipine 5mg |
| Placebo arm | Placebo comparator | Single dose per os placebo (microcrystalline cellulose) administration per day Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with 2 PI less then 3 Vs number of patients who performed ultrasound
Compare the rate of patients with two PIs on Dm + 7 (corresponding to D20-23 of the cycle) less than 3 out of the number of patients who performed the Doppler ultrasound in both arms.
Measured: seven days after initiation of treatment: Dm+7
Secondary outcomes (3)
Number of clinical pregnancies VS number of embryo transfers
Compare the rate of embryo transfers performed vs the rate of clinical pregnancies in both arms.
Clinical pregnancy is defined as pregnancy diagnosed by ultrasound with at least one gestational sac. Neither ectopic pregnancy nor pregnancy of undetermined location are considered to be pregnancy. This endpoint is measured by an independent blinded sonographer
Measured: 6 to 8 weeks after embryo transfer
number of miscarriages Vs number of embryo transfers
Compare the rate of embryo transfers performed vs the rate of miscariages in both arms Miscarriage is defined as the loss of a clinical intrauterine pregnancy before 20 weeks of amenorrhea, confirmed by ultrasound
Measured: before 20 weeks of menorrhea
Number of live births Vs number of embryo transfers
Compare the rate of embryo transfers performed vs the rate of live births in both arms Live birth is defined as the birth after 20 weeks of at least one child born alive. The birth of twins or more is counted as a live birth.
Measured: Delivery time starting 20 weeks of amenorrhea
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2021
- Study start8 Oct 2021 (estimated)
- Primary completion8 Oct 2023 (estimated)
- Study completion8 Sep 2024 (estimated)
Why it stopped: No participants enrolled
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Frozen Embryo TransferStudies of the same condition, open and under way.
- More trials run by University Hospital, MontpellierThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Montpellier
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Noémie RANISAVLJEVIC, MD, Study director, Arnaud de Villeneuve University Hospital, Montpellier
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04954196
- Sponsor's protocol ID
- RECHMPL20_0092
- Acronym
- AMLODIP
- Status last verified
- Mar 2023
- First submitted
- 5 Jul 2021
- Last updated
- 13 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Benefit of Amlodipine in HRT Cycle (Hormone Replacement Therapy) for Frozen Embryo Transfer in the Correction of Uterine Pulsatility Index: Randomized Controlled Double-blind Trial.
- ClinicalTrials.gov ID
- NCT04954196
- Acronym / sponsor ID
- AMLODIP / RECHMPL20_0092
- Conditions
- Frozen Embryo Transfer
- Keywords
- Frozen embryo transfer, Uterine artery pulsatility index, Implantation, Calcium channel blocker
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No participants enrolled
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University Hospital, MontpellierUniversity, hospital or other
- Study start
- 8 Oct 2021 (estimated)
- Primary completion
- 8 Oct 2023 (estimated)
- Study completion
- 8 Sep 2024 (estimated)
- First posted
- 8 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Embryo implantation depends on two main factors: embryo grading quality and endometrial receptivity.Numerous tools have been suggested to evaluate these two factors. Measurement of the pulsatility index (PI) of the uterine arteries is associated with extremely low chances of pregnancy when it is high, especially higher than 3.
A pilot study of women with premature ovarian failure with at least one of the uterine PIs greater than 3 showed the efficiency of nifedipine in uterine vascularization. This calcium channel blocker, used sublingually in this study, significantly lowered uterine PI in nearly half an hour.
We are therefore interested in exploring this accessible, non-invasive and inexpensive tool, in the evaluation of endometrial receptivity before an embryo transfer.
Detailed description
Embryo implantation is a key stage that depends on two main factors: embryo grading quality and endometrial receptivity. Numerous tools have been suggested to evaluate these two factors, without making it possible to predict with certainty the outcome of an embryo transfer in terms of pregnancy. However, some diagnostic tests have shown a good negative predictive value: it is the case of the measurement of the pulsatility index (PI) of the uterine arteries which is associated with extremely low chances of pregnancy when it is high, especially higher than 3 (Cacciatore et al., 1996; Steer et al., 1992).
The Pulsatility Index PI is calculated by the ratio between the maximum amplitude of the tracing and the mean velocity. It evolves according to downstream resistance. Uterine hypoperfusion would readily be associated with subfertility (Goswamy et al., 1988). The uterine arterial pulsatility index is easily accessible during pelvic ultrasound, with satisfactory intra- and inter-observer reproducibility (Steer et al., 1995). There is no significant difference between the measurement of the right and left uterine PI (Favre et al., 1993). Uterine PIs vary during the menstrual cycle (Goswamy and Steptoe, 1988) and depending on hormonal effects (de Ziegler et al., 1991; Strigini et al., 1995) or ovarian micropolycystic status (PCOS, syndrome of polycystic ovaries) of the patient (Resende et al., 2001). The impact of tobacco (Battaglia et al., 2011) and parity (Guedes-Martins et al., 2015) on uterine PIs is described in the literature. Age, although controversial, does not seem to have an impact on uterine PIs, at least in premenopausal women case (Check et al., 2000). Likewise, body mass index (BMI) could have an impact on PIs, as in increased PIs in obese women (Battaglia et al., 1996; Zeng et al., 2013) If high uterine PIs are associated with reduced chances of pregnancy, how can they be improved? A pilot study of women with premature ovarian failure with uterine PIs greater than 3 showed the efficiency of nifedipine in uterine vascularization. This calcium channel blocker, used sublingually in this study, significantly lowered uterine PI in nearly half an hour (Huissoud et al., 2004). This medication could therefore be promising in the treatment of patients in assisted medical reproduction (ART) for whom the measurements of the uterine PIs would be greater than 3 and therefore have lower chances of pregnancy.
This study aims to investigate weither the use of a calcium channel blocker (amlodipine) improves the value of uterine PIs in patients with at least one of the uterine PIs greater than 3, during a cycle for frozen embryo transfer (FET).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Amlodipine arm | Experimental | Drug: Amlodipine 5mgSingle dose per os Amlodipine 5mg administration per day |
| Placebo arm | Placebo comparator | Drug: PlaceboSingle dose per os placebo (microcrystalline cellulose) administration per day |
Who may qualify
- Ages
- 18 to 38 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Female subject
- 18 years (≤) age (≤) 38 years
- Patient scheduled for a blastocyst frozen transfer (vitrification on Day 5) on HRT cycle (hormone replacement therapy)
- Measurement of at least one of the two uterine PI (pulsatility index) greater than 3 (> 3) at the first monitoring Dm (corresponding to Day 13-Day 16 of the cycle)
- BMI ≤ 30 kg / m2
Key exclusion criteria (17 listed)
- Active smoker patient (at least one cigarette a day at the enrollment in the study)
- Oocyte recipient patient
- A pre-implantation genetic screening (PGS) is planned for the patient
- Patient with stage 3 or 4 endometriosis, or adenomyosis
- Contraindication to the use of amlodipine (recent myocardial infarction less than one month old, severe angina pectoris, severe hepatic insufficiency, treatment with ciclosporin, hypotension, hypersensitivity to amlodipine, dihydropyridine derivatives)
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 |
|---|---|---|
| Amlodipine 5mgAlso: AMLODIPINE ARROW GÉNÉRIQUES 5 mgHRT administration: On Day 1 of the cycle, HRT is planned in accordance with the department's standard practice. * The frozen embryo transfer will be performed 6 days after progesterone initiation. * The HRT will be maintained until the pregnancy test is performed: If the test is positive,HRT will be continued for up to 12 weeks of amenorrhea at the same doses and then gradually stopped. If the test is negative,HRT will be stopped gradually Amlodipine administration: On the day of the first monitoring Dm (corresponding to D13 D16 of the cycle), a single per os dose of amlodipine 5 mg is taken at night, neither the patient nor the investigator knows what drug is the patient getting. Monitoring is systematically performed the next morning.The treatment will be maintained until the pregnancy test is performed then if the test is positive, the treatment will be maintained for a total duration of 7 weeks. | Drug | Amlodipine arm |
| PlaceboHRT administration: On Day 1 of the cycle, HRT is planned in accordance with the department's standard practice. * The frozen embryo transfer will be performed 6 days after progesterone initiation. * The HRT will be maintained until the pregnancy test is performed: If the test is positive, HRT will be continued for up to 12 weeks of amenorrhea at the same doses and then gradually stopped. If the test is negative, HRT will be stopped gradually Placebo administration:On the day of the first monitoring Dm (corresponding to D13-D16 of the cycle), a single per os dose of placebo (Microcrystalline cellulose) is taken at night, neither the patient nor the investigator knows what drug is the patient getting. Monitoring is systematically performed the next morning.. The treatment will be maintained until the pregnancy test is performed, then if the test is positive, the treatment will be maintained for a total duration of 7 weeks. | Drug | Placebo arm |
Primary outcome
Number of patients with 2 PI less then 3 Vs number of patients who performed ultrasound
Time frame: seven days after initiation of treatment: Dm+7
Compare the rate of patients with two PIs on Dm + 7 (corresponding to D20-23 of the cycle) less than 3 out of the number of patients who performed the Doppler ultrasound in both arms.
3 secondary outcomes
Number of clinical pregnancies VS number of embryo transfers
Time frame: 6 to 8 weeks after embryo transfer
number of miscarriages Vs number of embryo transfers
Time frame: before 20 weeks of menorrhea
Number of live births Vs number of embryo transfers
Time frame: Delivery time starting 20 weeks of amenorrhea
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2023.
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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.
Noémie RANISAVLJEVIC, MD study director
Arnaud de Villeneuve University Hospital, Montpellier
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Amlodipine 5mg in people with Frozen Embryo Transfer, run by University Hospital, Montpellier.
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 8 inclusion and 17 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: withdrawn, as of the sponsor's last update on 13 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Number of patients with 2 PI less then 3 Vs number of patients who performed ultrasound (time frame: seven days after initiation of treatment: Dm+7). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Mar 2023.