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Completed

NCT Number: NCT03677336

Oral Dydrogesterone (OD) Versus Micronized Vaginal Progesterone (MVP) for Luteal Phase Support (LPS) in IVF/ICSI

Female inability to conceive a child. The purpose of this prospective randomized, double-blinded, double dummy, two-arm cross-over study is to investigate the difference on histological, transcriptional and immunological level in endometrium between 3x10mg Dydrogesterone oral tablets and 3x200 mg Micronized progesterone intravaginal capsules for the luteal support in egg cell donors. Beside that, the pharmacokinetics, the impact on the peripheral immunology (by blood sampling) and the microbiota (by genital swabs) will be investigated.

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Key information

Conditions

Infertility, Female Dydrogesterone Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genital Diseases Genital Diseases, Female Genital Diseases, Male Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Infertility Male Urogenital Diseases Physiological Effects of Drugs Progesterone Progestins Urogenital Diseases

Age range

18 year–35 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 4

Primary location

Centrum voor Reproductieve Geneeskunde

Jette, Brussels Capital, 1090, Belgium

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Oocyte donor candidates
  • Regularly cycling
  • BMI ≥18 and ≤ 29 kg/m2
  • Signed informed consent
  • Non-smokers.
  • AMH <7,53 and >1,18 ng/mL (90th and 10th percentile for healthy women aged 25-29 according to the used Elecsys® AMH kit by Roche)
  • PRL, T and TSH within the normal limits for the clinical laboratory, or considered not clinically significant by the investigator within 6 months prior or at screening

Exclusion criteria

  • Intra-uterine device
  • Previous enrollment
  • Evidence of cardiovascular, respiratory, urogenital, gastrointestinal/hepatic, hematologic/immunologic, HEENT (head, ears, eyes, nose, throat), dermatologic/connective tissue, musculoskeletal, metabolic/nutritional, endocrine, neurologic/psychiatric, allergy, recent major surgery (< 3 months), or other relevant diseases as revealed by history, physical examination and/or laboratory assessments which could limit participation in or completion of the study
  • Acute urogenital disease during the course of the study
  • Known allergic reactions to progesterone / dydrogesterone products (active substance or to any of the excipients)
  • Intake of any experimental drug or any participation in any other clinical trial within 30 days prior to study start.
  • Mental disability or any other lack of fitness, in the investigator's opinion, to preclude subjects in or to complete the study.
  • Current or recent substance abuse, including alcohol and tobacco (patients who stopped tobacco usage at least 3 months prior to screening visit would be allowed)
  • Refusal or inability to comply with the requirements of the study protocol for any reason, including scheduled clinic visits and laboratory tests.
  • Known or suspected progestogen dependent neoplasms (e.g. meningioma)
  • Serum progesterone level >1.5 ng/mL at ovulation triggering

Treatment and study plan

Dydrogesterone Oral Tablet

Drug

Tablet, oral, 10 mg, 3 times daily, starting on the day of oocyte retrieval in the morning and during 8 days

Other names: OD, Duphaston

Micronized progesterone

Drug

Capsule, vaginal, 200 mg, 3 times daily, starting on the day of oocyte retrieval in the morning and during 8 days

Other names: MVP, Utrogestan

Placebo Dydrogesterone oral tablet

Drug

Tablet, indistinguishable from dydrogesterone oral tablet

Other names: Placebo OD

Placebo Micronized progesterone

Drug

Capsule, indistinguishable from micronized vaginal progesterone capsules

Other names: Placebo MVP

Primary outcomes

  1. Molecular endometrial level using illumina RNA-seq

    Time frame: On the eight day (at 8am) of LPS intake

    To study the difference of OD versus MVP as LPS after controlled ovarian stimulation (COS) on the molecular endometrial level using Illumina RNA-seq on endometrial derived single cell suspensions

  2. Molecular endometrial level using immunohistochemistry

    Time frame: On the eight day (at 8am) of LPS intake

    To study the difference of OD versus MVP as LPS after controlled ovarian stimulation (COS) on the molecular endometrial level using immunohistochemistry on endometrial derived single cell suspensions

  3. Molecular endometrial level using flow cytometry

    Time frame: On the eight day (at 8am) of LPS intake

    To study the difference of OD versus MVP as LPS after controlled ovarian stimulation (COS) on the molecular endometrial level using flow cytometry on endometrial derived single cell suspensions

Secondary outcomes

  1. Difference in pharmacokinetic profile: Progesterone: AUC0-τ

    Time frame: On the first and eight day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose. One blood sample on the 9th, 10th and 11th day.

    using Liquid Chromatography with tandem Mass Spectrometry (LC-MS/MS)

  2. Difference in pharmacokinetic profile: Progesterone: AUC0-t

    Time frame: On the first day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose.

    using Liquid Chromatography with tandem Mass Spectrometry (LC-MS/MS)

  3. Difference in pharmacokinetic profile: Progesterone: Cmax

    Time frame: On the first and eight day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose. One blood sample on the 9th, 10th and 11th day.

    using Liquid Chromatography with tandem Mass Spectrometry (LC-MS/MS)

  4. Difference in pharmacokinetic profile: Progesterone: tmax

    Time frame: On the first and eight day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose. One blood sample on the 9th, 10th and 11th day.

    using Liquid Chromatography with tandem Mass Spectrometry (LC-MS/MS)

  5. Difference in pharmacokinetic profile: Progesterone: Ctrough

    Time frame: On the eight day of LPS intake: 1 hour before morning dose.

    using Liquid Chromatography with tandem Mass Spectrometry (LC-MS/MS)

  6. Difference in pharmacokinetic profile: Progesterone: λz

    Time frame: On the eight day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose. One blood sample on the 9th, 10th and 11th day.

    using Liquid Chromatography with tandem Mass Spectrometry (LC-MS/MS)

  7. Difference in pharmacokinetic profile: Progesterone: t1/2

    Time frame: On the eight day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose. One blood sample on the 9th, 10th and 11th day.

    using Liquid Chromatography with tandem Mass Spectrometry (LC-MS/MS)

  8. Difference in pharmacokinetic profile: Progesterone: CL/F

    Time frame: On the eight day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose. One blood sample on the 9th, 10th and 11th day.

    using Liquid Chromatography with tandem Mass Spectrometry (LC-MS/MS)

  9. Difference in pharmacokinetic profile: Progesterone: Vz/F

    Time frame: On the eight day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose. One blood sample on the 9th, 10th and 11th day.

    using Liquid Chromatography with tandem Mass Spectrometry (LC-MS/MS)

  10. Difference in pharmacokinetic profile: Dydrogesterone and 20α-dihydrodydrogesterone: AUC0-τ

    Time frame: On the first and eight day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose. One blood sample on the 9th, 10th and 11th day.

    using Liquid Chromatography with tandem Mass Spectrometry (LC-MS/MS)

  11. Difference in pharmacokinetic profile: Dydrogesterone and 20α-dihydrodydrogesterone: ratios of AUC0-τ of dydrogesterone and DHD

    Time frame: On the first and eight day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose. One blood sample on the 9th, 10th and 11th day.

    using Liquid Chromatography with tandem Mass Spectrometry (LC-MS/MS)

  12. Difference in pharmacokinetic profile: Dydrogesterone and 20α-dihydrodydrogesterone: AUC0-t

    Time frame: On the first day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose.

    using Liquid Chromatography with tandem Mass Spectrometry (LC-MS/MS)

  13. Difference in pharmacokinetic profile: Dydrogesterone and 20α-dihydrodydrogesterone: ratios of AUC0-t of dydrogesterone and DHD

    Time frame: On the first day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose.

    using Liquid Chromatography with tandem Mass Spectrometry (LC-MS/MS)

  14. Difference in pharmacokinetic profile: Dydrogesterone and 20α-dihydrodydrogesterone: Cmax

    Time frame: On the first and eight day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose. One blood sample on the 9th, 10th and 11th day.

    using Liquid Chromatography with tandem Mass Spectrometry (LC-MS/MS)

  15. Difference in pharmacokinetic profile: Dydrogesterone and 20α-dihydrodydrogesterone: ratios of Cmax of dydrogesterone and DHD

    Time frame: On the first and eight day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose. One blood sample on the 9th, 10th and 11th day.

    using Liquid Chromatography with tandem Mass Spectrometry (LC-MS/MS)

  16. Difference in pharmacokinetic profile: Dydrogesterone and 20α-dihydrodydrogesterone: tmax

    Time frame: On the first and eight day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose. One blood sample on the 9th, 10th and 11th day.

    using Liquid Chromatography with tandem Mass Spectrometry (LC-MS/MS)

  17. Difference in pharmacokinetic profile: Dydrogesterone and 20α-dihydrodydrogesterone: Ctrough

    Time frame: On the eight day of LPS intake: 1 hour before morning dose.

    using Liquid Chromatography with tandem Mass Spectrometry (LC-MS/MS)

  18. Difference in pharmacokinetic profile: Dydrogesterone and 20α-dihydrodydrogesterone: λz

    Time frame: On the eight day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose. One blood sample on the 9th, 10th and 11th day.

    using Liquid Chromatography with tandem Mass Spectrometry (LC-MS/MS)

  19. Difference in pharmacokinetic profile: Dydrogesterone and 20α-dihydrodydrogesterone: t1/2

    Time frame: On the eight day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose. One blood sample on the 9th, 10th and 11th day.

    using Liquid Chromatography with tandem Mass Spectrometry (LC-MS/MS)

  20. Difference in pharmacokinetic profile: Dydrogesterone and 20α-dihydrodydrogesterone: CL/F

    Time frame: On the eight day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose. One blood sample on the 9th, 10th and 11th day.

    using Liquid Chromatography with tandem Mass Spectrometry (LC-MS/MS)

  21. Difference in pharmacokinetic profile: Dydrogesterone and 20α-dihydrodydrogesterone: Vz/F

    Time frame: On the eight day of LPS intake: 1 hour before morning dose, 0.5 hour, 1 hour, 1 hour 30, 2 hours, 2 hours 30, 3 hours, 4 hours, 5 hours post-dose. One blood sample on the 9th, 10th and 11th day.

    using Liquid Chromatography with tandem Mass Spectrometry (LC-MS/MS)

  22. Difference in peripheral immunology

    Time frame: On the first and eight day of LPS intake, 1hour before morning dose at 9 am.

    To study the effects of OD versus MVP on the peripheral immunology (using flow cytometry to investigate T regulatory and T effector cells derived from peripheral blood)

  23. Difference in microbiota in the female genital tract

    Time frame: On the first and eight day of LPS intake, 1 hour before morning dose at 9 am.

    by cervical swab, a vaginal swab (posterior fornix) and an intra-uterine sample using an empty embryo catheter. Evaluation using 16S rRNA amplicon sequencing - Illumina miSeq

Sponsors and collaborators

Lead sponsor

CRG UZ Brussel

Other

Collaborators

  • Abbott
  • KU Leuven
  • Universitätsklinikum Hamburg-Eppendorf

Registry information

Official study title

Oral Dydrogesterone Versus Micronized Vaginal Progesterone for Luteal Phase Support in In Vitro Fertilisation (IVF)/ IntraCytoplasmic Sperm Injection (ICSI): Pharmacokinetics and the Impact on the Endometrium, the Microbiota of the Genital Tract and the Peripheral Immunology. Double Blind Crossover Study.

Important dates

Study start
2019
Primary completion
2020
Study completion
2020
First posted
Sep 19, 2018
Registry last updated
Dec 17, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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