NCT01909141

Brief 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). 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
100

participants targeted

Target at P75+ for early_phase_1

Timeline
Completed

Started Aug 2013

Shorter than P25 for early_phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 15, 2013

Completed
11 days until next milestone

First Posted

Study publicly available on registry

July 26, 2013

Completed
6 days until next milestone

Study Start

First participant enrolled

August 1, 2013

Completed
6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2014

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2014

Completed
11 months until next milestone

Results Posted

Study results publicly available

March 2, 2015

Completed
Last Updated

October 20, 2015

Status Verified

September 1, 2015

Enrollment Period

6 months

First QC Date

July 15, 2013

Results QC Date

February 3, 2015

Last Update Submit

September 30, 2015

Conditions

Keywords

letrozoleclomiphene citratepioglitazonemetforminovulation inductionPCOS

Outcome Measures

Primary Outcomes (1)

  • Ovulation Rate

    3 months

Secondary Outcomes (3)

  • Number of Follicles>18mm.

    3 months

  • Endometrial Thickness

    3 months

  • Pregnancy Rate

    3 months

Other Outcomes (1)

  • Safety of Pioglitazone as Regards Serum Creatinine

    3 months

Study Arms (2)

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.

Drug: induction of ovulation using letrozole-pioglitazone-metforminRadiation: transvaginal ultrasoundOther: body mass index (BMI) calculationOther: day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosteroneOther: pretreatment blood urea and serum creatinineOther: serum estradiol (E2) on day 12Other: serum progesterone on day 21Other: 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.

Drug: induction of ovulation using clomiphene citrate-pioglitazone-metforminRadiation: transvaginal ultrasoundOther: body mass index (BMI) calculationOther: day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosteroneOther: pretreatment blood urea and serum creatinineOther: serum estradiol (E2) on day 12Other: serum progesterone on day 21Other: blood urea and serum creatinine every month

Interventions

induction of ovulation will be done for arm 1 for 3 consecutive cycles unless pregnancy occured.

arm 1:letrozole-pioglitazone -metformin group

induction of ovulation for arm 2 will be done in 3 consecutive cycles unless pregnancy occured.

arm 2: clomiphene citrate-pioglitazone-metformin

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

arm 1:letrozole-pioglitazone -metformin grouparm 2: clomiphene citrate-pioglitazone-metformin

BMI will be calculated for all women by dividing the weight in kilograms by the height in meters squared

arm 1:letrozole-pioglitazone -metformin grouparm 2: clomiphene citrate-pioglitazone-metformin

baseline hormonal assay (day 3 FSH, LH, TSH and total testosterone) will be done for all women.

arm 1:letrozole-pioglitazone -metformin grouparm 2: clomiphene citrate-pioglitazone-metformin

blood urea and serum creatinine will be assayed before stating induction of ovulation to have baseline levels.

arm 1:letrozole-pioglitazone -metformin grouparm 2: clomiphene citrate-pioglitazone-metformin

serum E2 will be assayed on day 12 of the cycle for all women.

arm 1:letrozole-pioglitazone -metformin grouparm 2: clomiphene citrate-pioglitazone-metformin

serum progesterone will be assayed on day 21 for all women to monitor ovulation.

arm 1:letrozole-pioglitazone -metformin grouparm 2: clomiphene citrate-pioglitazone-metformin

blood urea and serum creatinine will be assayed every month during the treatment period to find out any hazards on kidney functions

arm 1:letrozole-pioglitazone -metformin grouparm 2: clomiphene citrate-pioglitazone-metformin

Eligibility Criteria

Age20 Years - 40 Years
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • years old
  • PCOS infertile women resistant to CC for3 cycles

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Cairo University

Cairo, Egypt

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Polycystic Ovary SyndromeInfertility

Interventions

Body Mass IndexLuteinizing HormoneThyrotropinTestosteroneBlood Urea Nitrogen

Condition Hierarchy (Ancestors)

Ovarian CystsCystsNeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital DiseasesGonadal DisordersEndocrine System Diseases

Intervention Hierarchy (Ancestors)

Body Weights and MeasuresBody ConstitutionPhysical ExaminationDiagnostic Techniques and ProceduresDiagnosisAnthropometryInvestigative TechniquesPhysiological PhenomenaBiometryEpidemiologic MeasurementsPublic HealthEnvironment and Public HealthGonadotropins, PituitaryGonadotropinsPeptide HormonesHormonesHormones, Hormone Substitutes, and Hormone AntagonistsPituitary Hormones, AnteriorPituitary HormonesPeptidesAmino Acids, Peptides, and ProteinsAndrostenolsAndrostenesAndrostanesSteroidsFused-Ring CompoundsPolycyclic CompoundsTestosterone CongenersGonadal Steroid HormonesGonadal HormonesBlood Chemical AnalysisClinical Chemistry TestsClinical Laboratory TechniquesKidney Function TestsDiagnostic Techniques, Urological

Results Point of Contact

Title
Dr. Ghada Abdel Fattah
Organization
Cairo University

Study Officials

  • Ghada Abdel Fattah Abdel Moety, lecturer

    Cairo University

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
early phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
lecturer of Obstetrics and Gynecology-Cairo University

Study Record Dates

First Submitted

July 15, 2013

First Posted

July 26, 2013

Study Start

August 1, 2013

Primary Completion

February 1, 2014

Study Completion

April 1, 2014

Last Updated

October 20, 2015

Results First Posted

March 2, 2015

Record last verified: 2015-09

Locations