Polycystic Ovary SyndromeEarly Phase 1NCT01909141
Ovulation Induction in Women With Clomiphene Citrate Resistant PCOS
A Early Phase 1 study testing induction of ovulation using letrozole-pioglitazone-metformin, induction of ovulation using clomiphene citrate-pioglitazone-metformin and transvaginal ultrasound in people with Polycystic Ovary Syndrome and Infertility, run by Cairo University at 1 site in Egypt.
Trial summary
Polycystic ovary syndrome (PCOS) affects 5-10% of women in childbearing age. Hyperinsulinemia contributes to chronic anovulation commonly encountered in women with PCOS. The first choice therapy is clomiphene citrate (CC). Read more about this study
- Who is it for?
- Ages 20 to 40 years, women only
- Conditions the study is for
- Polycystic Ovary Syndrome, Infertility
- What is being tested?
- induction of ovulation using letrozole-pioglitazone-metformin, induction of ovulation using clomiphene citrate-pioglitazone-metformin and transvaginal ultrasound
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteEgypt
- Study dates
- Aug 2013to Apr 2014
- Phase
- Early Phase 1
- 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 20 to 40 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 20-40 years old
- PCOS infertile women resistant to CC for3 cycles
Who cannot join
- presence of medical disorders as diabetes, hypertension, cardiac problems, liver or kidney diseases, hyperprolactinemia or thyroid dysfunction.
- use of gonadotropins before
- previous ovarian drilling
- presence of urinary symptoms especially bloody urine
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Combined Letrozole-metformin-pioglitazone Versus Combined Clomiphene Citrate-metformin-pioglitazone in Clomiphene Citrate-resistant Women With Polycystic Ovary Syndrome
Polycystic ovary syndrome (PCOS) affects 5-10% of women in childbearing age. Hyperinsulinemia contributes to chronic anovulation commonly encountered in women with PCOS. The first choice therapy is clomiphene citrate (CC). In CC resistant cases, the American College of Obstetrics and Gynecology (ACOG) recommends the use of insulin sensitizer metformin. Other insulin sensitizing agents include rosiglitazone and pioglitazone. Pioglitazone is said to improve fertility and ovulation in patients with PCOS.CC may be associated with poor endometrial thickening due to its antiestrogenic effect. Letrozole may improve this condition. In this study we will compare the effect of combined letrozole-metformin-pioglitazone with that of combined CC-metformin-pioglitazone in ovulation induction in CC-resistant PCOS women.
Read the detailed description
Polycystic ovary syndrome (PCOS) affects 5-10% of women in childbearing age. Hyperinsulinemia contributes to chronic anovulation commonly encountered in women with PCOS. The first choice therapy is clomiphene citrate (CC). In CC resistant cases, the ACOG recommends the use of insulin sensitizer metformin. Other insulin sensitizing agents include rosiglitazone and pioglitazone. Pioglitazone is said to improve fertility and ovulation in patients with PCOS.CC has a long half-life (2 weeks), and this may have a negative effect on the cervical mucus and endometrium, leading to discrepancy between ovulation and conception rates. There has been a search for a compound capable of inducing ovulation but devoid of the adverse antiestrogenic effects of CC. recent studies have suggested that letrozole, an aromatase inhibitor, does not possess the adverse antiestrogenic effects of CC and is associated with higher pregnancy rates than CC treatment in patients with PCOS.
In this study we shall compare the effect of combined letrozole-metformin-pioglitazone with that of combined CC-metformin-pioglitazone in ovulation induction in CC-resistant PCOS women.This will be a prospective comparative clinical trial in which 2 groups of women will be generated (groups A and B) using the sealed envelopes randomization method.Group A (40 women) will receive: letrozole 2.5 mg/day from 3rd day of the cycle for 5 days and (pioglitazone 15 mg + metformin 850 mg) once daily from 1st day of the cycle for 10 days. Group B (40 women) will receive clomiphene citrate 100 mg/day from 3rd day of the cycle for 5 days and (pioglitazone 15 mg + metformin 850 mg) once daily from 1st day of the cycle for 10 days. Ovulation will be monitored by vaginal ultrasound and serum estrogen and progesterone.
- Conditions
- Polycystic Ovary Syndrome, Infertility
- Being tested
- induction of ovulation using letrozole-pioglitazone-metformin, induction of ovulation using clomiphene citrate-pioglitazone-metformin, transvaginal ultrasound, body mass index (BMI) calculation, day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone
- Keywords
- letrozole, clomiphene citrate, pioglitazone, metformin, ovulation induction, PCOS
- Medical subject headings
- Polycystic Ovary Syndrome, Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
induction of ovulation using letrozole-pioglitazone-metforminDrug
induction of ovulation will be done for arm 1 for 3 consecutive cycles unless pregnancy occured.
induction of ovulation using clomiphene citrate-pioglitazone-metforminDrug
induction of ovulation for arm 2 will be done in 3 consecutive cycles unless pregnancy occured.
transvaginal ultrasoundRadiation
transvaginal ultrasound will be done starting from day 10 and every 48 hours until finding a follicle of > 18 mm or till day 20 of the cycle
body mass index (BMI) calculationOther
BMI will be calculated for all women by dividing the weight in kilograms by the height in meters squared
day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosteroneOther
baseline hormonal assay (day 3 FSH, LH, TSH and total testosterone) will be done for all women.
pretreatment blood urea and serum creatinineOther
blood urea and serum creatinine will be assayed before stating induction of ovulation to have baseline levels.
serum estradiol (E2) on day 12Other
serum E2 will be assayed on day 12 of the cycle for all women.
serum progesterone on day 21Other
serum progesterone will be assayed on day 21 for all women to monitor ovulation.
blood urea and serum creatinine every monthOther
blood urea and serum creatinine will be assayed every month during the treatment period to find out any hazards on kidney functions
| Study group | Role | What they receive |
|---|---|---|
| arm 1:letrozole-pioglitazone -metformin group | Active comparator | Arm 1 will receive letrozole 2.5 mg/day starting from the 3rd day of the cycle and for 5 days and (combined pioglitazone 15 mg+ metformin 850 mg) once daily from the first day of the cycle for 10 days. Receives: Drug: induction of ovulation using letrozole-pioglitazone-metformin; Radiation: transvaginal ultrasound; Other: body mass index (BMI) calculation; Other: day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone; Other: pretreatment blood urea and serum creatinine; Other: serum estradiol (E2) on day 12; Other: serum progesterone on day 21; Other: blood urea and serum creatinine every month |
| arm 2: clomiphene citrate-pioglitazone-metformin | Active comparator | Arm 2 will receive clomiphene citrate 100 mg/day starting from the 3rd day of the cycle for 5 days and (combined pioglitazone 15 mg + metformin 850 mg) once daily from the first day of the cycle for 10 days. Receives: Drug: induction of ovulation using clomiphene citrate-pioglitazone-metformin; Radiation: transvaginal ultrasound; Other: body mass index (BMI) calculation; Other: day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone; Other: pretreatment blood urea and serum creatinine; Other: serum estradiol (E2) on day 12; Other: serum progesterone on day 21; Other: blood urea and serum creatinine every month |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ovulation Rate
Measured: 3 months
Secondary outcomes (3)
Number of Follicles>18mm.
Measured: 3 months
Endometrial Thickness
Measured: 3 months
Pregnancy Rate
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2013 (estimated)
- Study startAug 2013
- Primary completionFeb 2014
- Study completionApr 2014
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 (1)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 Cairo UniversityThe 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cairo University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ghada Abdel Fattah, Cairo University
- Investigators
- Ghada Abdel Fattah Abdel Moety, lecturer, Principal investigator, Cairo University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01909141
- Sponsor's protocol ID
- fem2013
- Status last verified
- Sep 2015
- First submitted
- 15 Jul 2013
- Last updated
- 20 Oct 2015
- Results posted
- Yes, on ClinicalTrials.gov
Publications
El-khayat W, Abdel Moety G, Al Mohammady M, Hamed D. A randomized controlled trial of clomifene citrate, metformin, and pioglitazone versus letrozole, metformin, and pioglitazone for clomifene-citrate-resistant polycystic ovary syndrome. Int J Gynaecol Obstet. 2016 Feb;132(2):206-9. doi: 10.1016/j.ijgo.2015.06.063. Epub 2015 Nov 6.
PubMed 26613820
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combined Letrozole-metformin-pioglitazone Versus Combined Clomiphene Citrate-metformin-pioglitazone in Clomiphene Citrate-resistant Women With Polycystic Ovary Syndrome
- ClinicalTrials.gov ID
- NCT01909141
- Acronym / sponsor ID
- fem2013
- Conditions
- Polycystic Ovary Syndrome, Infertility
- Keywords
- letrozole, clomiphene citrate, pioglitazone, metformin, ovulation induction, PCOS
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Cairo UniversityUniversity, hospital or other
- Study start
- Aug 2013
- Primary completion
- Feb 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 26 Jul 2013 (estimated)
- Results
- Posted 2 Mar 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Polycystic ovary syndrome (PCOS) affects 5-10% of women in childbearing age. Hyperinsulinemia contributes to chronic anovulation commonly encountered in women with PCOS. The first choice therapy is clomiphene citrate (CC). In CC resistant cases, the American College of Obstetrics and Gynecology (ACOG) recommends the use of insulin sensitizer metformin. Other insulin sensitizing agents include rosiglitazone and pioglitazone. Pioglitazone is said to improve fertility and ovulation in patients with PCOS.CC may be associated with poor endometrial thickening due to its antiestrogenic effect. Letrozole may improve this condition. In this study we will compare the effect of combined letrozole-metformin-pioglitazone with that of combined CC-metformin-pioglitazone in ovulation induction in CC-resistant PCOS women.
Detailed description
Polycystic ovary syndrome (PCOS) affects 5-10% of women in childbearing age. Hyperinsulinemia contributes to chronic anovulation commonly encountered in women with PCOS. The first choice therapy is clomiphene citrate (CC). In CC resistant cases, the ACOG recommends the use of insulin sensitizer metformin. Other insulin sensitizing agents include rosiglitazone and pioglitazone. Pioglitazone is said to improve fertility and ovulation in patients with PCOS.CC has a long half-life (2 weeks), and this may have a negative effect on the cervical mucus and endometrium, leading to discrepancy between ovulation and conception rates. There has been a search for a compound capable of inducing ovulation but devoid of the adverse antiestrogenic effects of CC. recent studies have suggested that letrozole, an aromatase inhibitor, does not possess the adverse antiestrogenic effects of CC and is associated with higher pregnancy rates than CC treatment in patients with PCOS.
In this study we shall compare the effect of combined letrozole-metformin-pioglitazone with that of combined CC-metformin-pioglitazone in ovulation induction in CC-resistant PCOS women.This will be a prospective comparative clinical trial in which 2 groups of women will be generated (groups A and B) using the sealed envelopes randomization method.Group A (40 women) will receive: letrozole 2.5 mg/day from 3rd day of the cycle for 5 days and (pioglitazone 15 mg + metformin 850 mg) once daily from 1st day of the cycle for 10 days. Group B (40 women) will receive clomiphene citrate 100 mg/day from 3rd day of the cycle for 5 days and (pioglitazone 15 mg + metformin 850 mg) once daily from 1st day of the cycle for 10 days. Ovulation will be monitored by vaginal ultrasound and serum estrogen and progesterone.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| arm 1:letrozole-pioglitazone -metformin group | Active comparator | Drug: induction of ovulation using letrozole-pioglitazone-metformin, Radiation: transvaginal ultrasound, Other: body mass index (BMI) calculation, Other: day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone, Other: pretreatment blood urea and serum creatinine, Other: serum estradiol (E2) on day 12, Other: serum progesterone on day 21, Other: blood urea and serum creatinine every monthArm 1 will receive letrozole 2.5 mg/day starting from the 3rd day of the cycle and for 5 days and (combined pioglitazone 15 mg+ metformin 850 mg) once daily from the first day of the cycle for 10 days. |
| arm 2: clomiphene citrate-pioglitazone-metformin | Active comparator | Drug: induction of ovulation using clomiphene citrate-pioglitazone-metformin, Radiation: transvaginal ultrasound, Other: body mass index (BMI) calculation, Other: day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone, Other: pretreatment blood urea and serum creatinine, Other: serum estradiol (E2) on day 12, Other: serum progesterone on day 21, Other: blood urea and serum creatinine every monthArm 2 will receive clomiphene citrate 100 mg/day starting from the 3rd day of the cycle for 5 days and (combined pioglitazone 15 mg + metformin 850 mg) once daily from the first day of the cycle for 10 days. |
Who may qualify
- Ages
- 20 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- 20-40 years old
- PCOS infertile women resistant to CC for3 cycles
Key exclusion criteria (4 listed)
- presence of medical disorders as diabetes, hypertension, cardiac problems, liver or kidney diseases, hyperprolactinemia or thyroid dysfunction.
- use of gonadotropins before
- previous ovarian drilling
- presence of urinary symptoms especially bloody urine
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 |
|---|---|---|
| induction of ovulation using letrozole-pioglitazone-metformininduction of ovulation will be done for arm 1 for 3 consecutive cycles unless pregnancy occured. | Drug | arm 1:letrozole-pioglitazone -metformin group |
| induction of ovulation using clomiphene citrate-pioglitazone-metformininduction of ovulation for arm 2 will be done in 3 consecutive cycles unless pregnancy occured. | Drug | arm 2: clomiphene citrate-pioglitazone-metformin |
| transvaginal ultrasoundtransvaginal ultrasound will be done starting from day 10 and every 48 hours until finding a follicle of > 18 mm or till day 20 of the cycle | Radiation | arm 1:letrozole-pioglitazone -metformin group, arm 2: clomiphene citrate-pioglitazone-metformin |
| body mass index (BMI) calculationBMI will be calculated for all women by dividing the weight in kilograms by the height in meters squared | Other | arm 1:letrozole-pioglitazone -metformin group, arm 2: clomiphene citrate-pioglitazone-metformin |
| day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosteronebaseline hormonal assay (day 3 FSH, LH, TSH and total testosterone) will be done for all women. | Other | arm 1:letrozole-pioglitazone -metformin group, arm 2: clomiphene citrate-pioglitazone-metformin |
| pretreatment blood urea and serum creatinineblood urea and serum creatinine will be assayed before stating induction of ovulation to have baseline levels. | Other | arm 1:letrozole-pioglitazone -metformin group, arm 2: clomiphene citrate-pioglitazone-metformin |
| serum estradiol (E2) on day 12serum E2 will be assayed on day 12 of the cycle for all women. | Other | arm 1:letrozole-pioglitazone -metformin group, arm 2: clomiphene citrate-pioglitazone-metformin |
| serum progesterone on day 21serum progesterone will be assayed on day 21 for all women to monitor ovulation. | Other | arm 1:letrozole-pioglitazone -metformin group, arm 2: clomiphene citrate-pioglitazone-metformin |
| blood urea and serum creatinine every monthblood urea and serum creatinine will be assayed every month during the treatment period to find out any hazards on kidney functions | Other | arm 1:letrozole-pioglitazone -metformin group, arm 2: clomiphene citrate-pioglitazone-metformin |
Primary outcome
Ovulation Rate
Time frame: 3 months
3 secondary outcomes
Number of Follicles>18mm.
Time frame: 3 months
Endometrial Thickness
Time frame: 3 months
Pregnancy Rate
Time frame: 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26613820El-khayat W, Abdel Moety G, Al Mohammady M, Hamed D. A randomized controlled trial of clomifene citrate, metformin, and pioglitazone versus letrozole, metformin, and pioglitazone for clomifene-citrate-resistant polycystic ovary syndrome. Int J Gynaecol Obstet. 2016 Feb;132(2):206-9. doi: 10.1016/j.ijgo.2015.06.063. Epub 2015 Nov 6.
- Related InfoLink provided by the sponsor.
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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.
Ghada Abdel Fattah Abdel Moety, lecturer principal investigator
Cairo University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing induction of ovulation using letrozole-pioglitazone-metformin, induction of ovulation using clomiphene citrate-pioglitazone-metformin and transvaginal ultrasound in people with Polycystic Ovary Syndrome and Infertility, run by Cairo University at 1 site in Egypt.
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 4 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 20 Oct 2015. 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 Egypt. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 2 Mar 2015). 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?
Ovulation Rate (time frame: 3 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 NCT01909141, 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 20 Oct 2015.