Infertility, Female Infertility, Male InfertilityPhase 4OPTOMALHNCT01936077
Severe LH Suppressed Patients After Administration of a GnRH Antagonist
A Phase 4 study testing Recombinant LH (Luveris) in people with Infertility, Female Infertility, Male Infertility, run by Assuta Hospital Systems at 1 site in Israel.
Trial summary
The ideal stimulation protocol for ovarian stimulation is under constant debate, as we gain more pharmacological control over the patient hormonal milieu. Specifically, the debate focuses around the ideal LH levels. The concept of an "LH window" was suggested. Read more about this study
- Who is it for?
- Ages 18 to 39 years, women only
- Conditions the study is for
- Infertility, Female Infertility, Male Infertility
- What is being tested?
- Recombinant LH (Luveris)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteIsrael
- Study dates
- Jun 2010to Aug 2013
- Phase
- Phase 4
- 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 39 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 1. The patient is eligible for IVF and will be treated according to the Summary of Product Characteristics (SmPC) and routine practice in participating centres.
- 2. The patient must be willing and able to comply with the protocol for the duration of the study.
- 3. The patient has given written informed consent with the understanding that the consent may be withdrawn by her at any time without prejudice for her future medical care.
- 4. Must be hyper-responder to antagonist according definition
Who cannot join
- Ovarian, uterine or mammary cancer.
- Tumours of the hypothalamus and pituitary gland.
- Uterine myoma requiring treatment.
- Ovarian enlargement or cyst of unknown aetiology.
- A clinically significant systemic disease.
- Abnormal gynaecological bleeding of undetermined origin.
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- Known allergy or hypersensitivity to human gonadotrophin preparations.
- Entered previously into this study or simultaneous participation in another clinical study.
- Age > 39 yrs,
- BMI > 32 kg/m2,
- Patient with no cycles: PCOS or an anovulatory patient. -
Trial locations and contacts
1 site in 1 country.
About this study
Official title: To Define the Individual Need of Exogenous LH During Ovarian Stimulation for Severe LH Suppressed Patients After Administration of a GnRH Antagonist
The ideal stimulation protocol for ovarian stimulation is under constant debate, as we gain more pharmacological control over the patient hormonal milieu. Specifically, the debate focuses around the ideal LH levels. The concept of an "LH window" was suggested.
The need for a threshold level of LH is clearly demonstrated in hypogonado-tropic hypogonadism patients, but also in cycling patients receiving high doses of GnRH antagonist. The Ganirelix dose finding study demonstrated very low implantation rates in the high dose groups (1 mg, 2 mg).
Read more
The stimulation dynamics in these patients were remarkable for very low E2 and LH levels on the day of hCG. In fact, a functional state of hypogonadotropic hypogonadism is achieved, explaining the poor clinical results (1.5% implantation rate under 2 mg Ganirelix). The same protocol was repeated with added Luveris resulting in excellent pregnancy rates.
The recommended daily dose of GnRH antagonist is 0.25 mg which on the average provides a protection from premature LH surge, with moderate suppression of LH. Therefore, most patients do not need supplemented LH after the antagonist is initiated.
However, there is a subgroup of patients who hyper-respond to the antagonist (in 0.25 mg dose) with a sharp decrease in LH. This explains contradictory findings in the available studies. The basic assumption in the background of this proposal is that there is a wide range of pituitary responses to GnRH antagonist. Obeying a bell-shape curve, most women have an average response, however, some hypo-respond might ovulate prematurely, and others hyper-respond. In the latter cases, pituitary response will behave as if exposed to a higher dose.
How to identify an exposure to a presumed higher dose?
Below is a figure from the original paper. A close look indicates that the immediate response to all Ganirelix doses are similar in terms of LH drop, however, the big difference lies in the pituitary recovery 24 hours post Ganirelix dose.
While small doses allow for a quick recovery to almost pre-treatment LH levels, high doses result in incomplete recovery. Hence, it is reasonable to speculate that the high response to 0.25 mg dose will lead to slow or incomplete recovery of LH levels 24 hours post the initial dose.
It is estimated that about 15% of patients are antagonist hyper-responders. Efforts to individualize patient protocol must target this group as candidates for supplemented LH. This estimate is similar to study findings: Huirne et al Human Reproduction 2005, 20: 359.
- Being tested
- Recombinant LH (Luveris)
- Keywords
- Infertility, IVF, ovarian stimulation, rec LH, GnRH antagonist
- Medical subject headings
- Infertility, Infertility, Female, Infertility, Male
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recombinant LH (Luveris)Drug
Also called Luveris
150 IU recombinant LH daily.
| Study group | Role | What they receive |
|---|---|---|
| GnRH antagomnist hyper-responders | Experimental | Those defined as hyper-responders will be given recombinant LH. Receives: Drug: Recombinant LH (Luveris) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint will be the proportion of patients who, after receiving Cetrotide after 4 or 5 days of Gonal -F stimulation, are severely down-regulated.
If LH drops more than 50% from its baseline (as measured before Cetrotide) the patient is defined as "Cetrotide hyper-responder"
Measured: 24 hours after first administration of Cetrotide.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2013 (estimated)
- Study startJun 2010
- Primary completionMay 2013
- Study completionAug 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Infertility, Female Infertility, Male 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 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assuta Hospital Systems
- Sponsor type
- University, hospital or other
- Collaborators
- Maccabi Healthcare Services, Israel
- Responsible party
- Principal investigator, shahar kol, Assuta Hospital Systems
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01936077
- Sponsor's protocol ID
- 2010036
- Acronym
- OPTOMALH
- Status last verified
- Sep 2013
- First submitted
- 28 Oct 2010
- Last updated
- 5 Sep 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Kol S. Individualized Treatment from Theory to Practice: The Private Case of Adding LH during GnRH Antagonist-based Stimulation Protocol. Clin Med Insights Reprod Health. 2014 Oct 14;8:59-64. doi: 10.4137/CMRH.S17788. eCollection 2014.
PubMed 25452708
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- To Define the Individual Need of Exogenous LH During Ovarian Stimulation for Severe LH Suppressed Patients After Administration of a GnRH Antagonist
- ClinicalTrials.gov ID
- NCT01936077
- Acronym / sponsor ID
- OPTOMALH / 2010036
- Keywords
- Infertility, IVF, ovarian stimulation, rec LH, GnRH antagonist
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Assuta Hospital SystemsUniversity, hospital or other
- Collaborators
- Maccabi Healthcare Services, Israel
- Study start
- Jun 2010
- Primary completion
- May 2013 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 5 Sep 2013 (estimated)
- 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.
The ideal stimulation protocol for ovarian stimulation is under constant debate, as we gain more pharmacological control over the patient hormonal milieu. Specifically, the debate focuses around the ideal LH levels. The concept of an "LH window" was suggested.
The need for a threshold level of LH is clearly demonstrated in hypogonado-tropic hypogonadism patients, but also in cycling patients receiving high doses of GnRH antagonist. The Ganirelix dose finding study demonstrated very low implantation rates in the high dose groups (1 mg, 2 mg).
The stimulation dynamics in these patients were remarkable for very low E2 and LH levels on the day of hCG. In fact, a functional state of hypogonadotropic hypogonadism is achieved, explaining the poor clinical results (1.5% implantation rate under 2 mg Ganirelix). The same protocol was repeated with added Luveris resulting in excellent pregnancy rates.
The recommended daily dose of GnRH antagonist is 0.25 mg which on the average provides a protection from premature LH surge, with moderate suppression of LH. Therefore, most patients do not need supplemented LH after the antagonist is initiated.
However, there is a subgroup of patients who hyper-respond to the antagonist (in 0.25 mg dose) with a sharp decrease in LH. This explains contradictory findings in the available studies. The basic assumption in the background of this proposal is that there is a wide range of pituitary responses to GnRH antagonist. Obeying a bell-shape curve, most women have an average response, however, some hypo-respond might ovulate prematurely, and others hyper-respond. In the latter cases, pituitary response will behave as if exposed to a higher dose.
How to identify an exposure to a presumed higher dose?
Below is a figure from the original paper. A close look indicates that the immediate response to all Ganirelix doses are similar in terms of LH drop, however, the big difference lies in the pituitary recovery 24 hours post Ganirelix dose.
While small doses allow for a quick recovery to almost pre-treatment LH levels, high doses result in incomplete recovery. Hence, it is reasonable to speculate that the high response to 0.25 mg dose will lead to slow or incomplete recovery of LH levels 24 hours post the initial dose.
It is estimated that about 15% of patients are antagonist hyper-responders. Efforts to individualize patient protocol must target this group as candidates for supplemented LH. This estimate is similar to study findings: Huirne et al Human Reproduction 2005, 20: 359.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GnRH antagomnist hyper-responders | Experimental | Drug: Recombinant LH (Luveris)Those defined as hyper-responders will be given recombinant LH. |
Who may qualify
- Ages
- 18 to 39 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 1. The patient is eligible for IVF and will be treated according to the Summary of Product Characteristics (SmPC) and routine practice in participating centres.
- 2. The patient must be willing and able to comply with the protocol for the duration of the study.
- 3. The patient has given written informed consent with the understanding that the consent may be withdrawn by her at any time without prejudice for her future medical care.
- 4. Must be hyper-responder to antagonist according definition
Key exclusion criteria (11 listed)
- Ovarian, uterine or mammary cancer.
- Tumours of the hypothalamus and pituitary gland.
- Uterine myoma requiring treatment.
- Ovarian enlargement or cyst of unknown aetiology.
- A clinically significant systemic disease.
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 |
|---|---|---|
| Recombinant LH (Luveris)Also: Luveris150 IU recombinant LH daily. | Drug | GnRH antagomnist hyper-responders |
Primary outcome
The primary endpoint will be the proportion of patients who, after receiving Cetrotide after 4 or 5 days of Gonal -F stimulation, are severely down-regulated.
Time frame: 24 hours after first administration of Cetrotide.
If LH drops more than 50% from its baseline (as measured before Cetrotide) the patient is defined as "Cetrotide hyper-responder"
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2013.
- Derived from this study: PubMed 25452708Kol S. Individualized Treatment from Theory to Practice: The Private Case of Adding LH during GnRH Antagonist-based Stimulation Protocol. Clin Med Insights Reprod Health. 2014 Oct 14;8:59-64. doi: 10.4137/CMRH.S17788. eCollection 2014.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Recombinant LH (Luveris) in people with Infertility, Female Infertility, Male Infertility, run by Assuta Hospital Systems at 1 site in Israel.
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 4 inclusion and 11 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 5 Sep 2013. 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 Israel. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
The primary endpoint will be the proportion of patients who, after receiving Cetrotide after 4 or 5 days of Gonal -F stimulation, are severely down-regulated. (time frame: 24 hours after first administration of Cetrotide.). 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 NCT01936077, which also lists 1 linked publication.
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 5 Sep 2013.