ObesityPhase 4NCT02606500
Efficacy of Corifollitropin Alfa in Obese Women in Terms of Clinical and Molecular Parameters of IVF Success
A Phase 4 study testing Elonva in people with Obesity, run by University Medical Centre Ljubljana at 1 site in Slovenia.
Trial summary
The aim of the present study is to determine, whether clinical efficacy of 150 mcg of Corifollitropin alfa is the same in normal weighing and obese women. Furthermore, investigators want to determine whether oocytes retrieved from normal weighing and obese women, after COH using 150 mcg of Corifollitropin alfa, are of… Read more about this study
- Who is it for?
- Ages 18 to 38 years, women only
- Conditions the study is for
- Obesity
- What is being tested?
- Elonva
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteSlovenia
- Study dates
- Mar 2016to Mar 2017
- Phase
- Phase 4
- 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 18 to 38 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- BMI > 30 kg/m2
- BMI 18.5-24.9 kg/m2
Who cannot join
- polycystic ovary syndrome, severely abnormal sperm parameters, and age > 38 years
Trial locations and contacts
1 site in 1 country.
Slovenia1 site
Division of gynecology, Department of human reproduction
Ljubljana, 1000
About this study
The aim of the present study is to determine, whether clinical efficacy of 150 mcg of Corifollitropin alfa is the same in normal weighing and obese women. Furthermore, investigators want to determine whether oocytes retrieved from normal weighing and obese women, after COH using 150 mcg of Corifollitropin alfa, are of same quality on the molecular level.
Read the detailed description
The dosage of Corifollitropin alfa used for controlled ovarian hyperstimulation (COH) is adjusted according to the patient's body weight. Meaning, in women with a body weight ≤ 60 kg, a single dose of 100 mcg of Corifollitropin alfa is administered for COH and in women with a body weight > 60 kg, a single dose of 150 micrograms of Corifollitropin alfa is administered for COH. These two protocols are comparable in safety and efficacy of follicular stimulation.
On the other hand, knowledge about the clinical efficacy of 150 mcg of Corifollitropin alfa in obese women (BMI>30 kg/m2) is lacking.
Cumulus cells (CC) surround the oocyte and bi-directional communication between oocyte and CC is necessary for the development of mature and quality oocytes. It has been proposed, that analysis of genes, expressed in CC, can serve as an objective indicator of the oocyte's maturity and developmental potential. Expression of genes in CC as hyaluronan synthase 2 (HAS2), follicle-stimulating hormone receptor (FSHR), versican (VCAN), progesterone receptor (PR), vascular endothelial growth factor C (VEGFC), serine protease inhibitor E2 (SERPINE2), glutathione peroxidase (GPX3), pentraxin 3(PTX3) was reported to correlate with oocyte maturity and developmental potential.
The effect of Corifollitropin alfa on expression of these genes however, is unknown.
- Conditions
- Obesity
- Being tested
- Elonva
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ElonvaDrug
20 obese women will be the study group and 20 normal weighing women will be the control group. Both groups will receive 150 mcg of Elonva for controlled ovarian hyperstimulation (COH). Gonadotropin-releasing hormone (GnRH) antagonist will be used to prevent premature luteinizing hormone (LH) surge. Additional daily doses of 200 IU of recombinant follicle stimulating hormone (rFSH) will be used if necessary. Human chorionic gonadotropin (hCG) will be used for oocyte maturation. 2 mature follicles will be aspirated separately in each patient. Cumulus cell (CC) samples will be collected and stored on -80 oC for subsequent analysis. Clinical and molecular parameters of IVF success will be assessed and compared between the groups.
The exclusion criteria will be: polycystic ovary syndrome, severely abnormal sperm parameters, and age > 38 years.
| Study group | Role | What they receive |
|---|---|---|
| Elonva 150 mcg | Experimental | Elonva 150 mcg intramuscular daily obese Receives: Drug: Elonva |
| Elonva 100 mcg | Active comparator | Elonva 100 mcg intramuscular daily normal weight Receives: Drug: Elonva |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Oocytes Retrieved Per Patient
Number of oocytes obtained in the study group was compared to the number of oocytes obtained in the control group
Measured: 1 month
Number of Mature Oocytes
Number of mature oocytes obtained was compared between groups
Measured: 1 month
Number of Fertilized Oocytes
Measured: 1 month
Number of Frozen Embryos
Measured: 1 month
Biochemical Pregnancy Rate
Measured: 1 year
Secondary outcomes (1)
Real-time PCR Analysis of Genes That Were Proposed as Biomarkers of Oocyte Quality to Determine Effect of Corifollitropin Alpha on Oocyte Quality on Molecular Level
Expression of some genes that were proposed as biomarkers of oocyte quality was analysed in CC using real-time PCR. Relative expression values of genes were compared between mature oocytes derived from obese women and mature oocytes derived from normal weighing women.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2015 (estimated)
- Study startMar 2016
- Primary completionJan 2017
- Study completionMar 2017
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 (5)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by University Medical Centre LjubljanaThe 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 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Centre Ljubljana
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Tanja Burnik Papler, University Medical Centre Ljubljana
- Investigators
- Eda Vrtacnik Bokal, professor, Study chair, Head of the department of Human reproduction
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02606500
- Sponsor's protocol ID
- Merck-01
- Status last verified
- May 2018
- First submitted
- 6 Nov 2015
- Last updated
- 26 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Burnik Papler T, Vrtacnik Bokal E, Maver A, Kopitar AN, Lovrecic L. Transcriptomic Analysis and Meta-Analysis of Human Granulosa and Cumulus Cells. PLoS One. 2015 Aug 27;10(8):e0136473. doi: 10.1371/journal.pone.0136473. eCollection 2015.
PubMed 26313571Burnik Papler T, Vrtacnik Bokal E, Maver A, Lovrecic L. Specific gene expression differences in cumulus cells as potential biomarkers of pregnancy. Reprod Biomed Online. 2015 Apr;30(4):426-33. doi: 10.1016/j.rbmo.2014.12.011. Epub 2015 Jan 12.
PubMed 25682305Burnik Papler T, Vrtacnik Bokal E, Lovrecic L, Kopitar AN, Maver A. No specific gene expression signature in human granulosa and cumulus cells for prediction of oocyte fertilisation and embryo implantation. PLoS One. 2015 Mar 13;10(3):e0115865. doi: 10.1371/journal.pone.0115865. eCollection 2015.
PubMed 25769026Devjak R, Fon Tacer K, Juvan P, Virant Klun I, Rozman D, Vrtacnik Bokal E. Cumulus cells gene expression profiling in terms of oocyte maturity in controlled ovarian hyperstimulation using GnRH agonist or GnRH antagonist. PLoS One. 2012;7(10):e47106. doi: 10.1371/journal.pone.0047106. Epub 2012 Oct 17.
PubMed 23082142Vrtacnik-Bokal E, Virant Klun I, Verdenik I. Follicular oestradiol and VEGF after GnRH antagonists or GnRH agonists in women with PCOS. Reprod Biomed Online. 2009 Jan;18(1):21-8. doi: 10.1016/s1472-6483(10)60420-8.
PubMed 19146765
Study at a glance
From the registry record, last updated by the sponsor on 26 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Corifollitropin Alfa in Obese Women in Terms of Clinical and Molecular Parameters of IVF Success
- ClinicalTrials.gov ID
- NCT02606500
- Acronym / sponsor ID
- Merck-01
- Conditions
- Obesity
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- University Medical Centre LjubljanaUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Mar 2016 (actual)
- Primary completion
- Jan 2017 (actual)
- Study completion
- Mar 2017 (actual)
- First posted
- 17 Nov 2015 (estimated)
- Results
- Posted 26 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the present study is to determine, whether clinical efficacy of 150 mcg of Corifollitropin alfa is the same in normal weighing and obese women. Furthermore, investigators want to determine whether oocytes retrieved from normal weighing and obese women, after COH using 150 mcg of Corifollitropin alfa, are of same quality on the molecular level.
Detailed description
The dosage of Corifollitropin alfa used for controlled ovarian hyperstimulation (COH) is adjusted according to the patient's body weight. Meaning, in women with a body weight ≤ 60 kg, a single dose of 100 mcg of Corifollitropin alfa is administered for COH and in women with a body weight > 60 kg, a single dose of 150 micrograms of Corifollitropin alfa is administered for COH. These two protocols are comparable in safety and efficacy of follicular stimulation.
On the other hand, knowledge about the clinical efficacy of 150 mcg of Corifollitropin alfa in obese women (BMI>30 kg/m2) is lacking.
Cumulus cells (CC) surround the oocyte and bi-directional communication between oocyte and CC is necessary for the development of mature and quality oocytes. It has been proposed, that analysis of genes, expressed in CC, can serve as an objective indicator of the oocyte's maturity and developmental potential. Expression of genes in CC as hyaluronan synthase 2 (HAS2), follicle-stimulating hormone receptor (FSHR), versican (VCAN), progesterone receptor (PR), vascular endothelial growth factor C (VEGFC), serine protease inhibitor E2 (SERPINE2), glutathione peroxidase (GPX3), pentraxin 3(PTX3) was reported to correlate with oocyte maturity and developmental potential.
The effect of Corifollitropin alfa on expression of these genes however, is unknown.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Elonva 150 mcg | Experimental | Drug: ElonvaElonva 150 mcg intramuscular daily obese |
| Elonva 100 mcg | Active comparator | Drug: ElonvaElonva 100 mcg intramuscular daily normal weight |
Who may qualify
- Ages
- 18 to 38 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- BMI > 30 kg/m2
- BMI 18.5-24.9 kg/m2
Key exclusion criteria (1 listed)
- polycystic ovary syndrome, severely abnormal sperm parameters, and age > 38 years
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 |
|---|---|---|
| Elonva20 obese women will be the study group and 20 normal weighing women will be the control group. Both groups will receive 150 mcg of Elonva for controlled ovarian hyperstimulation (COH). Gonadotropin-releasing hormone (GnRH) antagonist will be used to prevent premature luteinizing hormone (LH) surge. Additional daily doses of 200 IU of recombinant follicle stimulating hormone (rFSH) will be used if necessary. Human chorionic gonadotropin (hCG) will be used for oocyte maturation. 2 mature follicles will be aspirated separately in each patient. Cumulus cell (CC) samples will be collected and stored on -80 oC for subsequent analysis. Clinical and molecular parameters of IVF success will be assessed and compared between the groups. The exclusion criteria will be: polycystic ovary syndrome, severely abnormal sperm parameters, and age > 38 years. | Drug | Elonva 100 mcg, Elonva 150 mcg |
Primary outcome
Number of Oocytes Retrieved Per Patient
Time frame: 1 month
Number of oocytes obtained in the study group was compared to the number of oocytes obtained in the control group
Number of Mature Oocytes
Time frame: 1 month
Number of mature oocytes obtained was compared between groups
Number of Fertilized Oocytes
Time frame: 1 month
Number of Frozen Embryos
Time frame: 1 month
Biochemical Pregnancy Rate
Time frame: 1 year
1 secondary outcome
Real-time PCR Analysis of Genes That Were Proposed as Biomarkers of Oocyte Quality to Determine Effect of Corifollitropin Alpha on Oocyte Quality on Molecular Level
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 26313571Burnik Papler T, Vrtacnik Bokal E, Maver A, Kopitar AN, Lovrecic L. Transcriptomic Analysis and Meta-Analysis of Human Granulosa and Cumulus Cells. PLoS One. 2015 Aug 27;10(8):e0136473. doi: 10.1371/journal.pone.0136473. eCollection 2015.
- Background: PubMed 25682305Burnik Papler T, Vrtacnik Bokal E, Maver A, Lovrecic L. Specific gene expression differences in cumulus cells as potential biomarkers of pregnancy. Reprod Biomed Online. 2015 Apr;30(4):426-33. doi: 10.1016/j.rbmo.2014.12.011. Epub 2015 Jan 12.
- Background: PubMed 25769026Burnik Papler T, Vrtacnik Bokal E, Lovrecic L, Kopitar AN, Maver A. No specific gene expression signature in human granulosa and cumulus cells for prediction of oocyte fertilisation and embryo implantation. PLoS One. 2015 Mar 13;10(3):e0115865. doi: 10.1371/journal.pone.0115865. eCollection 2015.
- Background: PubMed 23082142Devjak R, Fon Tacer K, Juvan P, Virant Klun I, Rozman D, Vrtacnik Bokal E. Cumulus cells gene expression profiling in terms of oocyte maturity in controlled ovarian hyperstimulation using GnRH agonist or GnRH antagonist. PLoS One. 2012;7(10):e47106. doi: 10.1371/journal.pone.0047106. Epub 2012 Oct 17.
- Background: PubMed 19146765Vrtacnik-Bokal E, Virant Klun I, Verdenik I. Follicular oestradiol and VEGF after GnRH antagonists or GnRH agonists in women with PCOS. Reprod Biomed Online. 2009 Jan;18(1):21-8. doi: 10.1016/s1472-6483(10)60420-8.
Related trials for Obesity
RecruitingObservational study
Endoscopic Sleeve Gastroplasty (ESG) Prospective Trial for Obesity (EGO-Trial)
Obesity
Active, not recruitingPhase 4
Effects of Sequential Therapy With Mexidol® (Intravenous) and Mexidol® FORTE 250 (Oral) on Functional Brain Activity Assessed by Functional Magnetic Resonance Imaging and Biochemical Parameters in Patients With Chronic Cerebral Ischemia: A Comparison of Patients With and Without Metabolic Disorders
Metabolic Abnormalities, Obesity & Overweight
Recruiting
Exercise Training and Vitamin D Metabolism
Obesity & Overweight, Vitamin D
Recruiting
Metabolic Health, Bones and Nuts During Weight Loss in Adults
Weight Loss, Bone Density
Active, not recruiting
Effect of Probiotics on Insulin Sensitivity in Overweight and Obese Pregnancy
Obesity & Overweight, Gestational Diabetes Mellitus (GDM)
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.
Eda Vrtacnik Bokal, professor study chair
Head of the department of Human reproduction
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 Elonva in people with Obesity, run by University Medical Centre Ljubljana at 1 site in Slovenia.
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 2 inclusion and 1 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 26 Nov 2018. 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 Slovenia. 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?
Yes. Results are posted in the registry (first posted 26 Nov 2018). 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?
Number of Oocytes Retrieved Per Patient (time frame: 1 month). The study lists 5 primary outcomes in all. 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 NCT02606500, which also lists 5 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 26 Nov 2018.