Polycystic Ovary SyndromePhase 4NCT03353948
The Effect of a Liraglutide on IVF in Obese PCOS
A Phase 4 study testing MET and COMBI in people with Polycystic Ovary Syndrome and Obesity, run by University Medical Centre Ljubljana.
Trial summary
The aim of this study was to evaluate the impact of low dose liraglutide in combination with metformin compared to metformin alone on IVF pregnancy rate (PR) and cumulatively PR (IVF and spontaneous) in infertile obese women with PCOS who had been previously poor responders regarding weight reduction with lifestyle… Read more about this study
- Who is it for?
- Ages 18 to 37 years, women only
- Conditions the study is for
- Polycystic Ovary Syndrome, Obesity, Infertility, Female
- What is being tested?
- MET and COMBI
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- 1 Sep 2014to 1 Sep 2016
- 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 37 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 18 years old to 38 years old
- polycystic ovary syndrome (rotterdam criteria)
- BMI of 30 kg/m² or higher
- Infertility
- Before IVF
Who cannot join
- type 1 or type 2 diabetes mellitus
- history of carcinoma
- Cushing's syndrome or congenital (non-classic) adrenal hyperplasia
- personal or family history of MEN 2
- significant cardiovascular, kidney or hepatic disease
- the use of medications known or suspected to affect reproductive or metabolic functions
- the use of statins, within 90 days prior to study entry no other ovarian pathology normal male semen
About this study
Official title: The Effect of Liraglutide on Pregnancy Rates in Obese Women With PCOS Undergoing in Vitro Fertilization: a Pilot Randomized Study
The aim of this study was to evaluate the impact of low dose liraglutide in combination with metformin compared to metformin alone on IVF pregnancy rate (PR) and cumulatively PR (IVF and spontaneous) in infertile obese women with PCOS who had been previously poor responders regarding weight reduction with lifestyle modification and resistant to first line reproductive treatments.
Read the detailed description
Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility, in particular when PCOS is linked to obesity. Obese PCOS has poor IVF outcomes associated with impaired oocyte and embryo parameters and morphology. The purpose of this pilot prospective study was to investigate the effect of the novel medical therapy (combination of metformin and liraglutide (COMBI)) in the specific infertile obese PCOS population. GLP-1 has been investigated in regulation of reproductive system in animal models. Current observations suggest that it directly regulates kisspeptin and GnRH expression and that ovaries express GLP-1 mRNA. In obese PCOS, GLP-1 receptor agonist liraglutide provided positive effects on weight reduction and glucose homeostasis
- Conditions
- Polycystic Ovary Syndrome, Obesity, Infertility, Female
- Being tested
- MET, COMBI
- Keywords
- Polycystic Ovary Syndrome, Obesity, Infertility, IVF
- Medical subject headings
- Polycystic Ovary Syndrome, Obesity, Infertility, Female, Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
METDrug
Also called Glucophage tbl
In the MET group metformin was initiated at a dose of 500 mg once per day and increased by 500 mg every 3 days up to 1000 mg BID per os for 12 weeks. After 1 month IVF was done.
COMBIDrug
Also called Victoza 6 mg/ml solution for injection in pre-filled pen
In the COMBI group the initial dose of MET was 500 mg for at least 2 wk and gradually increased to a final dose of 1000 mg BID. Liraglutide 1.2 mg QD s.c. was added after first two weeks of monotherapy with MET. After 1 month IVF was done.
| Study group | Role | What they receive |
|---|---|---|
| Metfrormin group (MET) | Active comparator | Drug: Metformin Receives: Drug: MET |
| COMBI group (COMBI) | Active comparator | Drug: liraglutide Receives: Drug: COMBI |
What is being measured
The primary outcome is the main question the study is designed to answer.
IVF pregnancy rates
Clinical pregnancy rate defined as the presence of a fetal heart beat by ultrasound
Measured: 14 days
BMI
Patient's BMI was defined as the patient's body mass in kilograms divided by the square of their height in meters.
Measured: Patient's BMI was measured at the beginning and every four weeks during 12 weeks of clinical trial. ]
Cumulative pregnancy rates
Number of all pregnancies (IVF pregnancies and spontaneous pregnancies) per patient
Measured: The pregnancies were collected by phone interview after one year
Secondary outcomes (2)
Oocyte nuclear maturation
The number of metaphase 2 oocytes, metaphase 1 oocytes, and germinal vesicles
Measured: 2 days
Embryo quality
The embryo quality assessed by standard cleavage stage embryo grading system on day 3 of embryo culture. For any embryos grown to day 5, the embryo quality assessed by standard blastocyst grading system on day 5 of embryo culture
Measured: 6 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2017
- Study start1 Sep 2014
- Primary completion31 May 2016
- Study completion1 Sep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Polycystic Ovary SyndromeStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Centre Ljubljana
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Vesna Salamun, University Medical Centre Ljubljana
- Investigators
- Eda Vrtacnik Bokal, professor, Study chair, UMC Ljubljana
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03353948
- Sponsor's protocol ID
- Obese PCOS IVF
- Status last verified
- Nov 2017
- First submitted
- 15 Nov 2017
- Last updated
- 27 Nov 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Jensterle Sever M, Kocjan T, Pfeifer M, Kravos NA, Janez A. Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin. Eur J Endocrinol. 2014 Feb 7;170(3):451-9. doi: 10.1530/EJE-13-0797. Print 2014 Mar.
PubMed 24362411Salamun V, Rizzo M, Lovrecic L, Hocevar K, Papler Burnik T, Janez A, Jensterle M, Vrtacnik Bokal E, Peterlin B, Maver A. The Endometrial Transcriptome of Metabolic and Inflammatory Pathways During the Window of Implantation Is Deranged in Infertile Obese Polycystic Ovarian Syndrome Women. Metab Syndr Relat Disord. 2022 Sep;20(7):384-394. doi: 10.1089/met.2021.0149. Epub 2022 Jul 13.
PubMed 35834645
Study at a glance
From the registry record, last updated by the sponsor on 27 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Liraglutide on Pregnancy Rates in Obese Women With PCOS Undergoing in Vitro Fertilization: a Pilot Randomized Study
- ClinicalTrials.gov ID
- NCT03353948
- Acronym / sponsor ID
- Obese PCOS IVF
- Conditions
- Polycystic Ovary Syndrome, Obesity, Infertility, Female
- Keywords
- Polycystic Ovary Syndrome, Obesity, Infertility, IVF
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University Medical Centre LjubljanaUniversity, hospital or other
- Study start
- 1 Sep 2014 (actual)
- Primary completion
- 31 May 2016 (actual)
- Study completion
- 1 Sep 2016 (actual)
- First posted
- 27 Nov 2017 (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.
The aim of this study was to evaluate the impact of low dose liraglutide in combination with metformin compared to metformin alone on IVF pregnancy rate (PR) and cumulatively PR (IVF and spontaneous) in infertile obese women with PCOS who had been previously poor responders regarding weight reduction with lifestyle modification and resistant to first line reproductive treatments.
Detailed description
Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility, in particular when PCOS is linked to obesity. Obese PCOS has poor IVF outcomes associated with impaired oocyte and embryo parameters and morphology. The purpose of this pilot prospective study was to investigate the effect of the novel medical therapy (combination of metformin and liraglutide (COMBI)) in the specific infertile obese PCOS population. GLP-1 has been investigated in regulation of reproductive system in animal models. Current observations suggest that it directly regulates kisspeptin and GnRH expression and that ovaries express GLP-1 mRNA. In obese PCOS, GLP-1 receptor agonist liraglutide provided positive effects on weight reduction and glucose homeostasis
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metfrormin group (MET) | Active comparator | Drug: METDrug: Metformin |
| COMBI group (COMBI) | Active comparator | Drug: COMBIDrug: liraglutide |
Who may qualify
- Ages
- 18 to 37 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 18 years old to 38 years old
- polycystic ovary syndrome (rotterdam criteria)
- BMI of 30 kg/m² or higher
- Infertility
- Before IVF
Key exclusion criteria (7 listed)
- type 1 or type 2 diabetes mellitus
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 |
|---|---|---|
| METAlso: Glucophage tblIn the MET group metformin was initiated at a dose of 500 mg once per day and increased by 500 mg every 3 days up to 1000 mg BID per os for 12 weeks. After 1 month IVF was done. | Drug | Metfrormin group (MET) |
| COMBIAlso: Victoza 6 mg/ml solution for injection in pre-filled penIn the COMBI group the initial dose of MET was 500 mg for at least 2 wk and gradually increased to a final dose of 1000 mg BID. Liraglutide 1.2 mg QD s.c. was added after first two weeks of monotherapy with MET. After 1 month IVF was done. | Drug | COMBI group (COMBI) |
Primary outcome
IVF pregnancy rates
Time frame: 14 days
Clinical pregnancy rate defined as the presence of a fetal heart beat by ultrasound
BMI
Time frame: Patient's BMI was measured at the beginning and every four weeks during 12 weeks of clinical trial. ]
Patient's BMI was defined as the patient's body mass in kilograms divided by the square of their height in meters.
Cumulative pregnancy rates
Time frame: The pregnancies were collected by phone interview after one year
Number of all pregnancies (IVF pregnancies and spontaneous pregnancies) per patient
2 secondary outcomes
Oocyte nuclear maturation
Time frame: 2 days
Embryo quality
Time frame: 6 days
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 27 Nov 2017.
- Background: PubMed 24362411Jensterle Sever M, Kocjan T, Pfeifer M, Kravos NA, Janez A. Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin. Eur J Endocrinol. 2014 Feb 7;170(3):451-9. doi: 10.1530/EJE-13-0797. Print 2014 Mar.
- Derived from this study: PubMed 35834645Salamun V, Rizzo M, Lovrecic L, Hocevar K, Papler Burnik T, Janez A, Jensterle M, Vrtacnik Bokal E, Peterlin B, Maver A. The Endometrial Transcriptome of Metabolic and Inflammatory Pathways During the Window of Implantation Is Deranged in Infertile Obese Polycystic Ovarian Syndrome Women. Metab Syndr Relat Disord. 2022 Sep;20(7):384-394. doi: 10.1089/met.2021.0149. Epub 2022 Jul 13.
- Individual participant dataSharing planned: Undecided
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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.
Eda Vrtacnik Bokal, professor study chair
UMC Ljubljana
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing MET and COMBI in people with Polycystic Ovary Syndrome and Obesity, run by University Medical Centre Ljubljana.
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 7 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 27 Nov 2017. 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. 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?
IVF pregnancy rates (time frame: 14 days). The study lists 3 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 NCT03353948, which also lists 2 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 27 Nov 2017.