Polycystic Ovary SyndromePhase 4NCT02280057
Trial With Metformin in Women With Polycystic Ovary Syndrome
A Phase 4 study testing Metformin in people with Polycystic Ovary Syndrome, run by Herning Hospital at 1 site in Denmark.
Trial summary
The investigators wanted to elucidate the effects of metformin in Polycystic Ovary Syndrome (PCOS) by performing a randomized, double-blinded, placebo-controlled cross-over study. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Polycystic Ovary Syndrome
- What is being tested?
- Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 56 participants
- Where
- 1 siteDenmark
- Study dates
- Sep 2001to Dec 2002
- 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 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- testosterone value above the upper normal limit and
- oligo- or amenorrhea,
Who cannot join
- periclimacteric gonadotrophin values,
- hyperprolactinaemia,
- diabetes mellitus,
- impaired thyroid,
- renal or hepatic function,
- hormonal treatment,
- pregnancy,
- lactation or a wish for fertility treatment.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized, Cross-over Trial With Metformin in Women With Polycystic Ovary Syndrome
The investigators wanted to elucidate the effects of metformin in Polycystic Ovary Syndrome (PCOS) by performing a randomized, double-blinded, placebo-controlled cross-over study.
Read the detailed description
Eligible women who gave written informed consent were assigned to 6 months of treatment with either 850 mg of metformin or placebo twice daily, followed by a wash-out period of 3 months before cross-over to the alternate treatment for another 6 months. Randomization defining treatment sequence was done at inclusion by random number tables. The appearance of the tablets was identical, and patients and investigators were blinded to treatment allocation. The randomization code was stored in a closed envelope until all participants had finished the treatment. Participants were seen by one of the investigators before inclusion and every second month during treatment periods, always in the morning after an overnight fast of at least 8 h. They were weighed wearing light clothing. Waist circumference was measured at the umbilical level and hip circumference at the trochanter region. Systolic and diastolic blood pressure was measured with a semiautomatic blood pressure monitor and a blood sample was drawn for immediate analysis without respect to bleeding periods. All participants registered their bleeding periods in a calendar during both study periods and the 3 months wash-out period. Calculation of sample size was based on the assumption that at least 50% of the women would experience at least 30% more menstrual periods on metformin than on placebo. Based on a power of 90 (b = 0.10) to detect a significant difference [two-sided P-value of 0.05], the minimum sampling size was calculated to 44 subjects.
We also assumed a 10% drop-out rate, and thus aimed at including 50 women. As drop-out rate quickly rose higher than expected, we decided to include 60 women. In the intention-to-treat analysis, the values of each participant after 6 months of metformin or placebo were compared with the baseline values. Linear regression analysis with the changes in testosterone and homeostasis model assessment (HOMA) index as dependent variables was performed to examine potential relations between the changes. The per protocol analysis included data from participants completing both study periods, i.e. the difference between the values of each participant after placebo and metformin, respectively, was calculated, and a significance test performed on the differences.
- Conditions
- Polycystic Ovary Syndrome
- Being tested
- Metformin, Placebo
- Keywords
- PCOS, metformin, obesity, randomized controlled trial
- Medical subject headings
- Polycystic Ovary Syndrome, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Metformin 1500 mg (=2 pills) per day in six months
PlaceboDrug
2 pills per day in six months; pills look like metformin pills
| Study group | Role | What they receive |
|---|---|---|
| Metformin | Active comparator | Metformin 850 mg x 2 in six months Receives: Drug: Metformin |
| Placebo | Placebo comparator | Placebo 2 tablets daily for six months Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Testosterone (Levels of free testosterone)
Levels of free testosterone
Measured: six months
Secondary outcomes (1)
Insulin sensitivity (measured homeostasis model assessment (HOMA) index)
Insulin sensitivity measured homeostasis model assessment (HOMA) index
Measured: Six months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2014 (estimated)
- Study startSep 2001
- Primary completionDec 2002
- Study completionDec 2002
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Polycystic Ovary SyndromeStudies 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
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Herning Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- GEA A/S Denmark
- Responsible party
- Principal investigator, Finn Friis Lauszus, Herning Hospital
- Investigators
- Finn F Lauszus, MD, PhD, Principal investigator, Gyn Dept. Herning Hospital, Herning, Denmark
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02280057
- Sponsor's protocol ID
- 2166-00
- Status last verified
- Feb 2017
- First submitted
- 28 Oct 2014
- Last updated
- 23 Feb 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Trolle B, Flyvbjerg A, Kesmodel U, Lauszus FF. Efficacy of metformin in obese and non-obese women with polycystic ovary syndrome: a randomized, double-blinded, placebo-controlled cross-over trial. Hum Reprod. 2007 Nov;22(11):2967-73. doi: 10.1093/humrep/dem271. Epub 2007 Aug 31.
PubMed 17766923Trolle B, Lauszus FF, Frystyk J, Flyvbjerg A. Adiponectin levels in women with polycystic ovary syndrome: impact of metformin treatment in a randomized controlled study. Fertil Steril. 2010 Nov;94(6):2234-8. doi: 10.1016/j.fertnstert.2010.01.057. Epub 2010 Mar 2.
PubMed 20189560Greibe E, Trolle B, Bor MV, Lauszus FF, Nexo E. Metformin lowers serum cobalamin without changing other markers of cobalamin status: a study on women with polycystic ovary syndrome. Nutrients. 2013 Jul 5;5(7):2475-82. doi: 10.3390/nu5072475.
PubMed 23857221Madsen HN, Lauszus FF, Trolle B, Ingerslev HJ, Torring N. Impact of metformin on anti-Mullerian hormone in women with polycystic ovary syndrome: a secondary analysis of a randomized controlled trial. Acta Obstet Gynecol Scand. 2015 May;94(5):547-51. doi: 10.1111/aogs.12605. Epub 2015 Mar 4.
PubMed 25736975
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Cross-over Trial With Metformin in Women With Polycystic Ovary Syndrome
- ClinicalTrials.gov ID
- NCT02280057
- Acronym / sponsor ID
- 2166-00
- Conditions
- Polycystic Ovary Syndrome
- Keywords
- PCOS, metformin, obesity, randomized controlled trial
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Herning HospitalUniversity, hospital or other
- Collaborators
- GEA A/S Denmark
- Study start
- Sep 2001
- Primary completion
- Dec 2002 (actual)
- Study completion
- Dec 2002 (actual)
- First posted
- 31 Oct 2014 (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 investigators wanted to elucidate the effects of metformin in Polycystic Ovary Syndrome (PCOS) by performing a randomized, double-blinded, placebo-controlled cross-over study.
Detailed description
Eligible women who gave written informed consent were assigned to 6 months of treatment with either 850 mg of metformin or placebo twice daily, followed by a wash-out period of 3 months before cross-over to the alternate treatment for another 6 months. Randomization defining treatment sequence was done at inclusion by random number tables. The appearance of the tablets was identical, and patients and investigators were blinded to treatment allocation. The randomization code was stored in a closed envelope until all participants had finished the treatment. Participants were seen by one of the investigators before inclusion and every second month during treatment periods, always in the morning after an overnight fast of at least 8 h. They were weighed wearing light clothing. Waist circumference was measured at the umbilical level and hip circumference at the trochanter region. Systolic and diastolic blood pressure was measured with a semiautomatic blood pressure monitor and a blood sample was drawn for immediate analysis without respect to bleeding periods. All participants registered their bleeding periods in a calendar during both study periods and the 3 months wash-out period. Calculation of sample size was based on the assumption that at least 50% of the women would experience at least 30% more menstrual periods on metformin than on placebo. Based on a power of 90 (b = 0.10) to detect a significant difference [two-sided P-value of 0.05], the minimum sampling size was calculated to 44 subjects.
We also assumed a 10% drop-out rate, and thus aimed at including 50 women. As drop-out rate quickly rose higher than expected, we decided to include 60 women. In the intention-to-treat analysis, the values of each participant after 6 months of metformin or placebo were compared with the baseline values. Linear regression analysis with the changes in testosterone and homeostasis model assessment (HOMA) index as dependent variables was performed to examine potential relations between the changes. The per protocol analysis included data from participants completing both study periods, i.e. the difference between the values of each participant after placebo and metformin, respectively, was calculated, and a significance test performed on the differences.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metformin | Active comparator | Drug: MetforminMetformin 850 mg x 2 in six months |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo 2 tablets daily for six months |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- testosterone value above the upper normal limit and
- oligo- or amenorrhea,
Key exclusion criteria (8 listed)
- periclimacteric gonadotrophin values,
- hyperprolactinaemia,
- diabetes mellitus,
- impaired thyroid,
- renal or hepatic function,
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 |
|---|---|---|
| MetforminMetformin 1500 mg (=2 pills) per day in six months | Drug | Metformin |
| Placebo2 pills per day in six months; pills look like metformin pills | Drug | Placebo |
Primary outcome
Testosterone (Levels of free testosterone)
Time frame: six months
Levels of free testosterone
1 secondary outcome
Insulin sensitivity (measured homeostasis model assessment (HOMA) index)
Time frame: Six months
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 23 Feb 2017.
- Results publication: PubMed 17766923Trolle B, Flyvbjerg A, Kesmodel U, Lauszus FF. Efficacy of metformin in obese and non-obese women with polycystic ovary syndrome: a randomized, double-blinded, placebo-controlled cross-over trial. Hum Reprod. 2007 Nov;22(11):2967-73. doi: 10.1093/humrep/dem271. Epub 2007 Aug 31.
- Results publication: PubMed 20189560Trolle B, Lauszus FF, Frystyk J, Flyvbjerg A. Adiponectin levels in women with polycystic ovary syndrome: impact of metformin treatment in a randomized controlled study. Fertil Steril. 2010 Nov;94(6):2234-8. doi: 10.1016/j.fertnstert.2010.01.057. Epub 2010 Mar 2.
- Results publication: PubMed 23857221Greibe E, Trolle B, Bor MV, Lauszus FF, Nexo E. Metformin lowers serum cobalamin without changing other markers of cobalamin status: a study on women with polycystic ovary syndrome. Nutrients. 2013 Jul 5;5(7):2475-82. doi: 10.3390/nu5072475.
- Results publication: PubMed 25736975Madsen HN, Lauszus FF, Trolle B, Ingerslev HJ, Torring N. Impact of metformin on anti-Mullerian hormone in women with polycystic ovary syndrome: a secondary analysis of a randomized controlled trial. Acta Obstet Gynecol Scand. 2015 May;94(5):547-51. doi: 10.1111/aogs.12605. Epub 2015 Mar 4.
- Individual participant dataSharing planned: No
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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.
Finn F Lauszus, MD, PhD principal investigator
Gyn Dept. Herning Hospital, Herning, Denmark
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 Metformin in people with Polycystic Ovary Syndrome, run by Herning Hospital at 1 site in Denmark.
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 8 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 23 Feb 2017. 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 Denmark. 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. 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 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?
Testosterone (Levels of free testosterone) (time frame: six months). 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 NCT02280057, which also lists 4 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 23 Feb 2017.