Polycystic Ovary SyndromePhase 4NCT00159575
Metformin in Assisted Reproduction-MET-AR-study
A Phase 4 study of Polycystic Ovary Syndrome, run by Norwegian University of Science and Technology at 2 sites in Norway.
Trial summary
Aim of study: To investigate whether four months of metformin treatment before IVF (in-vitro-fertilisation) or ICSI (intra-cytoplasmic-sperm-injection) might increase clinical pregnancy rate in normal-weight (body mass index [BMI] below 28 kg/m3) in PCOS (polycystic ovarian syndrome) women. 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
- Polycystic Ovary Syndrome
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 2 sitesNorway
- Study dates
- Mar 2005to Apr 2010
- 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 38 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Fulfilling Rotterdam criteria for PCOS
- Infertility more than 1 year
- First or second cycle of IVF/ICSI treatment
- Age below 38 years at inclusion
- BMI below 28 kg/m3 at inclusion
- Willing to be randomised to 4 months metformin or placebo
- Signed written informed consent
Who cannot join
- Not suitable for starting dose 112.5 IE
- Basal FSH above 10 IU/L
- Known renal disease or s-creatinine above 110 umol/L
- Known liver disease or s-ALAT above 80 IU/L
- Known alcoholism or drug abuse
- Known diabetes mellitus or fasting plasma glucose above 7 mmol/L
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- Corticosteroid treatment (oral)
- Treatment with cimetidine, anticoagulants, erythromycin or other macrolides
- Hyperprolactinemia (PRL above 700 mIU/L)
- Abnormal thyroid function tests
- Known congenital adrenal hyperplasia
- Androgen secreting tumours
- Cushing syndrome
- Metformin treatment within the last one month prior to screening
- Unfit to participate for any other reason
Trial locations and contacts
2 sites in 1 country.
Norway2 sites
Sigrun Kjøtrød
Trondheim, 7006
Fertility UNit- -St Olavs Hospital
Trondheim, 7046
About this study
Official title: Metformin Treatment Before IVF / ICSI in Non-obese Women With Polycystic Ovarian Syndrome
Aim of study: To investigate whether four months of metformin treatment before IVF (in-vitro-fertilisation) or ICSI (intra-cytoplasmic-sperm-injection) might increase clinical pregnancy rate in normal-weight (body mass index [BMI] below 28 kg/m3) in PCOS (polycystic ovarian syndrome) women.
Read the detailed description
PCOS is an hormonal disease including hyperandrogenism, oligo-or anovulation and/or polycystic ovaries by ultrasound. PCOS women often suffer insulin resistance or even diabetes risk as well as a full blown metabolic disease.
These women often suffer infertility due to their lack of regular ovulations. Metformin is a well known anti-diabetic drug, and in some PCOS women metformin might decrease the hyperandrogenism, improve insulin resistance and give more regular ovulations. Thereby increase chance of pregnancy. Our hypothesis is that metformin will increase clinical pregnancy rates both spontaneously and following IVF/ICSI.
- Conditions
- Polycystic Ovary Syndrome
- Being tested
- Metformin / Placebo treatment for 4 months
- Keywords
- Polycystic ovarian syndrome, Clinical pregnancy rate, Oligo- or anovulation
- 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.
Metformin / Placebo treatment for 4 monthsDrug
M: Metformin 2000mg daily- 12-14 weeks of pretreatment + metformin 2000mg daily through conventional IVF ending on the day of pregnancy test; IE. 14 days after embryo transfer. P: Or identical placebo treatment for the same period
| Study group | Role | What they receive |
|---|---|---|
| M: Metformin P: Placebo | Experimental | Not described Receives: Drug: Metformin / Placebo treatment for 4 months |
What is being measured
The primary outcome is the main question the study is designed to answer.
To investigate whether four months of Metformin treatment before IVF (in-vitro-fertilisation) or ICSI (intra-cytoplasmic sperm injection) will increase clinical pregnancy rate in normal weight PCOS-women
Measured: Vaginal ultrasound in pregnancy week 7
Secondary outcomes (2)
Spontaneous pregnancy rates during the pretreatment period, Spontaneous abortion rates (I or II trim.abortions), Live birth rates,
Measured: Vaginal ultrasound in pregnancy week 7
Number of oocytes collected, Embryo quality, Number of days of gonadotrophin treatment, Dose of gonadotrophin, total per cycle and daily, s-estradiol on day of hCG-administration, Occurrence of ovarian hyperstimulation syndrome (OHSS)
Measured: All data evaluated at study end, from september 2009 onwards
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2005 (estimated)
- Study startMar 2005
- Primary completionAug 2009
- Study completionApr 2010
Why it stopped: Slow patient recruitment and expiry of study medication(aug2009)
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 Norwegian University of Science and TechnologyThe 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- Norwegian University of Science and Technology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sven Carlsen, MD,PhD, Study chair, St Olavs Hospital- Endocrinological section
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00159575
- Sponsor's protocol ID
- MET-AR study -PCOS 5
- Other IDs
- EUDRACTNR. 2004-001124-20
- Status last verified
- Jan 2012
- First submitted
- 9 Sep 2005
- Last updated
- 5 Jan 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Kjotrod SB, Carlsen SM, Rasmussen PE, Holst-Larsen T, Mellembakken J, Thurin-Kjellberg A, Haapaniemikouru K, Morin-Papunen L, Humaidan P, Sunde A, von During V. Use of metformin before and during assisted reproductive technology in non-obese young infertile women with polycystic ovary syndrome: a prospective, randomized, double-blind, multi-centre study. Hum Reprod. 2011 Aug;26(8):2045-53. doi: 10.1093/humrep/der154. Epub 2011 May 23.
PubMed 21606131Tso LO, Costello MF, Albuquerque LET, Andriolo RB, Macedo CR. Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2020 Dec 21;12(12):CD006105. doi: 10.1002/14651858.CD006105.pub4.
PubMed 33347618
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metformin Treatment Before IVF / ICSI in Non-obese Women With Polycystic Ovarian Syndrome
- ClinicalTrials.gov ID
- NCT00159575
- Acronym / sponsor ID
- MET-AR study -PCOS 5
- Conditions
- Polycystic Ovary Syndrome
- Keywords
- Polycystic ovarian syndrome, Clinical pregnancy rate, Oligo- or anovulation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow patient recruitment and expiry of study medication(aug2009)
- Enrolment
- 150 participants (actual)
- Lead sponsor
- Norwegian University of Science and TechnologyUniversity, hospital or other
- Study start
- Mar 2005
- Primary completion
- Aug 2009 (actual)
- Study completion
- Apr 2010 (actual)
- First posted
- 12 Sep 2005 (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.
Aim of study: To investigate whether four months of metformin treatment before IVF (in-vitro-fertilisation) or ICSI (intra-cytoplasmic-sperm-injection) might increase clinical pregnancy rate in normal-weight (body mass index [BMI] below 28 kg/m3) in PCOS (polycystic ovarian syndrome) women.
Detailed description
PCOS is an hormonal disease including hyperandrogenism, oligo-or anovulation and/or polycystic ovaries by ultrasound. PCOS women often suffer insulin resistance or even diabetes risk as well as a full blown metabolic disease.
These women often suffer infertility due to their lack of regular ovulations. Metformin is a well known anti-diabetic drug, and in some PCOS women metformin might decrease the hyperandrogenism, improve insulin resistance and give more regular ovulations. Thereby increase chance of pregnancy. Our hypothesis is that metformin will increase clinical pregnancy rates both spontaneously and following IVF/ICSI.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| M: Metformin P: Placebo | Experimental | Drug: Metformin / Placebo treatment for 4 months |
Who may qualify
- Ages
- 18 to 38 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Fulfilling Rotterdam criteria for PCOS
- Infertility more than 1 year
- First or second cycle of IVF/ICSI treatment
- Age below 38 years at inclusion
- BMI below 28 kg/m3 at inclusion
Key exclusion criteria (15 listed)
- Not suitable for starting dose 112.5 IE
- Basal FSH above 10 IU/L
- Known renal disease or s-creatinine above 110 umol/L
- Known liver disease or s-ALAT above 80 IU/L
- Known alcoholism or drug abuse
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 |
|---|---|---|
| Metformin / Placebo treatment for 4 monthsM: Metformin 2000mg daily- 12-14 weeks of pretreatment + metformin 2000mg daily through conventional IVF ending on the day of pregnancy test; IE. 14 days after embryo transfer. P: Or identical placebo treatment for the same period | Drug | M: Metformin P: Placebo |
Primary outcome
To investigate whether four months of Metformin treatment before IVF (in-vitro-fertilisation) or ICSI (intra-cytoplasmic sperm injection) will increase clinical pregnancy rate in normal weight PCOS-women
Time frame: Vaginal ultrasound in pregnancy week 7
2 secondary outcomes
Spontaneous pregnancy rates during the pretreatment period, Spontaneous abortion rates (I or II trim.abortions), Live birth rates,
Time frame: Vaginal ultrasound in pregnancy week 7
Number of oocytes collected, Embryo quality, Number of days of gonadotrophin treatment, Dose of gonadotrophin, total per cycle and daily, s-estradiol on day of hCG-administration, Occurrence of ovarian hyperstimulation syndrome (OHSS)
Time frame: All data evaluated at study end, from september 2009 onwards
Results and safety
The study was stopped early (reason given: Slow patient recruitment and expiry of study medication(aug2009)). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2012.
- Results publication: PubMed 21606131Kjotrod SB, Carlsen SM, Rasmussen PE, Holst-Larsen T, Mellembakken J, Thurin-Kjellberg A, Haapaniemikouru K, Morin-Papunen L, Humaidan P, Sunde A, von During V. Use of metformin before and during assisted reproductive technology in non-obese young infertile women with polycystic ovary syndrome: a prospective, randomized, double-blind, multi-centre study. Hum Reprod. 2011 Aug;26(8):2045-53. doi: 10.1093/humrep/der154. Epub 2011 May 23.
- Derived from this study: PubMed 33347618Tso LO, Costello MF, Albuquerque LET, Andriolo RB, Macedo CR. Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2020 Dec 21;12(12):CD006105. doi: 10.1002/14651858.CD006105.pub4.
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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.
Sven Carlsen, MD,PhD study chair
St Olavs Hospital- Endocrinological section
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study of Polycystic Ovary Syndrome, run by Norwegian University of Science and Technology at 2 sites in Norway.
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 7 inclusion and 15 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: stopped early, as of the sponsor's last update on 5 Jan 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Norway. 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 was stopped early (reason given: Slow patient recruitment and expiry of study medication(aug2009)). Results are not available in the source record.
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?
To investigate whether four months of Metformin treatment before IVF (in-vitro-fertilisation) or ICSI (intra-cytoplasmic sperm injection) will increase clinical pregnancy rate in normal weight PCOS-women (time frame: Vaginal ultrasound in pregnancy week 7). 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 NCT00159575, 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 5 Jan 2012.