E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Women having low ovarian reserve undergoing IVF/ICSI treatment |
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E.1.1.1 | Medical condition in easily understood language |
Women having low number of eggs remaining within the ovaries (i.e. aged ovaries, undergoing IVF |
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E.1.1.2 | Therapeutic area | Body processes [G] - Reproductive physiologi cal processes [G08] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To examine whether supplementation of DHEA for at least twelve weeks prior to and during ovarian stimulation increases the number of oocytes retrieved and the clinical pregnancy rates following IVF/ICSI treatment. • To evaluate the feasibility of conducting a large multicentre randomised controlled trial of DHEA versus Placebo in women affected with ovarian ageing undergoing IVF/ICSI treatment. |
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E.2.2 | Secondary objectives of the trial |
• To examine the effect of DHEA on developmental competence of oocytes as measured by molecular markers 1. Expression levels of a panel of 9 cumulus markers of oocyte competence: FSH-R, LH-R, pentraxin 3, cyclooxygenase 2, hyaluronic acid synthase 2, the BMP antagonist-Gremlin, epidermal growth factor (EGF)-like signalling molecules amphiregulin, epiregulin and betacellulin; 2. Nutritional finger printing: measuring glucose, pyruvate and lactate utilization from the culture media as the energy consumption by the oocyte from the medium vary depending on its ability to develop to the blastocyst stage) • To examine the effect of DHEA on chromosomal anomalies (aneuploidy rates) in immature and unfertilized oocytes. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Women aged ≥23 years with diminished ovarian reserve Antral follicle count of ≤10 or Anti-Mullerian hormone levels <5pmol/L 2. Women undergoing IVF/ICSI treatment 3. Women must have a regular spontaneous menstrual cycle of 21 – 35 days 4. Women must be willing and comply with scheduled visits, treatment plan and laboratory tests. |
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E.4 | Principal exclusion criteria |
1. BMI >35 Kg/M2 2. Women with a single ovary 3. Untreated hydrosalpinx/ submucous fibroid/ Endometrial polyp at the start of treatment 4. Any history of seizure disorders 5. Previous participation in this trial in an earlier treatment cycle 6. Any known endocrine disorders such as congenital adrenal hyperplasia, thyroid diseases, hyperprolactinemia 7. Known allergy to DHEA 8. Diabetic women on insulin (Insulin lower the DHEA levels and might lower the effectiveness of DHEA supplements) |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Number of oocytes retrieved and clinical pregnancy rates • Recruitment rates, compliance of recruited participants with DHEA/ Placebo intake and follow up rates |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The last time point to obtain all the primary outcome measures would be when the pregnant participant has their early pregnancy scan following IVF/ICSI treatment. i.e. about 20 weeks after they entered into the trial. |
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E.5.2 | Secondary end point(s) |
- Expression levels of a panel of 9 cumulus markers of oocyte competence: FSH-R, LH-R, pentraxin 3, cyclooxygenase 2, hyaluronic acid synthase 2, the BMP antagonist-Gremlin, epidermal growth factor (EGF)-like signalling molecules amphiregulin, epiregulin and betacellulin, quantified by real-time PCR in cumulus cells cut from 1-2 cumulus oocyte complex/patient at the time of cumulus removal for ICSI. - Aneuploidy rates in the immature oocytes and unfertilized oocytes. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The samples for evaluation of secondary outcome measures will be obtained on the day of egg collection (about 14 weeks after they entered into the trial). The samples will be stored frozen until the assessment (molecular analysis and comparative genomic hybridization), which is planned to be performed in batches. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The trial will be closed when the last recruited participant has her early pregnancy scan, if she conceives. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 29 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 29 |