E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
low ovarian reserve |
Baja respuesta ovárica |
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E.1.1.1 | Medical condition in easily understood language |
Premature ovarian aging |
Envejecimiento del ovario |
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E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036602 |
E.1.2 | Term | Premature ovarian failure |
E.1.2 | System Organ Class | 100000004872 |
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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 |
Define a pilot study to determine telomeric length distribution in granulosa cells to evaluate if telomerase reactivation via sexual steroids (DANAZOL), in patients with low ovarian reserve, is feasible. |
Estudio piloto para determinar la distribución de la longitud telomérica en las células de la granulosa para evaluar si la reactivación a través de esteroides sexuales (DANAZOL), en pacientes con baja reserva ovárica, es factible. |
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E.2.2 | Secondary objectives of the trial |
-Describe telomere length and accumulation of short telomeres in blood. -Determine if there is a correlation between telomeric factors in blood and granulosa cells in order to find new biomarkers for early detection of premature low ovarian reserve. -Determination of the DNA damage inside the cell nucleus and the percentage of activation of proteins involved in senescence. -Study of the status of telomere protection by shelterins in blood and GC. -Study the beneficial effects of steroid treatment on fertilization parameters -Examination of the ovarian volume and reserve before and after treatment with sexual steroids and compared with normal ovarian reserve patients. -Analysis of the total number of oocytes retrieved (particularly MII oocytes) after induction of ovulation in all groups. -Analysis of the quality of embryos (morphology of embryos), the implantation rate and the clinical pregnancy rate . -Assessment and recording of adverse events |
-Describir longitud de los telómeros y acumulación de telómeros cortos en sangre. -Determinar si existe una correlación entre los factores teloméricos en las células de la sangre y la granulosa con el fin de encontrar nuevos biomarcadores para la detección temprana de baja reserva ovárica prematura. -Determinar el daño al ADN dentro del núcleo celular y el porcentaje de activación de proteínas involucradas en la senescencia. -Estudiar el estado de la protección de los telómeros en sangre y GC. -Estudiar los efectos beneficiosos del tratamiento con esteroides en los parámetros de fertilización. -Examinar volumen y reserva ovárica antes y después del tratamiento con esteroides sexuales y en comparación con pacientes normales con reserva ovárica. -Analizar el número total de ovocitos recuperados después de la inducción de la ovulación en todos los grupos. -Analizar calidad de los embriones, tasa de implantación y tasa de embarazo clínico. -Evaluar y registrar eventos adversos. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Provide signed and dated informed consent form. -Willing to comply with all study procedures and be available for the duration of the study. This include the decision to use contraception methods different to sexual hormones, such as the use of condoms, during the treatment with Danazol. -female, aged 30 to 45 years old. -In good general health as evidenced by medical history or diagnosed with body mass index between 18 and 30Kg/m2. -Women with normal (AMH value must be equal or higher than 2ng/ml) or compromised ovarian reserve (defined as AMH <2ng/ml). -Not having had any steroid hormones for one month. |
-Proporcionar un formulario de consentimiento informado firmado y fechado. -Está dispuesto a cumplir con todos los procedimientos del estudio y estar disponible durante la duración del estudio. Esto incluye la decisión de usar métodos anticonceptivos diferentes a las hormonas sexuales, como el uso de condones, durante el tratamiento con Danazol. - Mujeres, de 30 a 45 años (ambas inclusive) -Buena salud general como lo demuestra la historia clínica o diagnosticado con un índice de masa corporal entre 18 y 30 Kg / m2. -Mujeres con reserva ovárica normal (el valor de AMH debe ser igual o superior a 2 ng / ml) o la reserva ovárica comprometida (definida como AMH <2 ng / ml). -No haber tomado hormonas esteroideas el mes previo. |
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E.4 | Principal exclusion criteria |
-Pregnancy or lactation. -Taking other sexual hormones. -Women with diseases in heart, liver or kidney or tumors which depend on male sexual hormones or hormone-dependent tumour. -Women taking anticonvulsants, medicaments for diabetes, anticoagulants and anti-hypertension: Ciclosporin and tacrolimus and other steroids and statins. -Women suffering irregular genital bleeding or with thrombus or thromboembolic diseases. -Known allergic reactions to components of the study product (cornstarch and lactose). -Having received ovulation induction drugs within one month before the inclusion in the study. -Anything that would place the individual at increased risk or preclude the individual’s full compliance with or completion of the study. -Simultaneous participation in another clinical trial or previous participation in this study. -Participation in another clinical study 2 months before inclusion in the present study that could affect its objectives |
-Embarazo o lactancia. -Tomar otras hormonas sexuales. - Mujeres con enfermedades en el corazón, hígado o riñón o tumores que dependen de hormonas sexuales masculinas o tumores dependientes de hormonas. -Mujeres que toman anticonvulsivos, medicamentos para la diabetes, anticoagulantes y antihipertensores: ciclosporina y tacrolimus y otros esteroides y estatinas. -Mujeres con sangrado genital irregular o con trombo o enfermedades tromboembólicas. - Reacciones alérgicas conocidas a los componentes del producto del estudio (almidón de maíz y lactosa). -Haber recibido medicamentos de inducción a la ovulación dentro de un mes antes de la inclusión en el estudio. -Cualquier cosa que ponga a la persona en mayor riesgo o que impida su total cumplimiento o finalización del estudio. - Participación simultánea en otro ensayo clínico o participación previa en este estudio. -Participación en otro estudio clínico 2 meses antes de la inclusión en el presente estudio que podría afectar el cumplimiento de los objetivos |
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E.5 End points |
E.5.1 | Primary end point(s) |
Reduction in the percentage of dysfunctional telomeres in Granulosa Cells. |
Reducción en el porcentaje de telómeros disfuncionales en células de la granulosa |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After Eighth visit (36 h +/- 2h post induction) for women with low ovarian reserve and Fifth visit for woman with normal ovarian reserve |
Después de la visita octava ( 36 horas post inducción) para mujeres con baja reserva ovárica y después de la quinta visita para mujeres con reserva ovárica normal |
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E.5.2 | Secondary end point(s) |
1-Accumulation of short telomeres,telomerase activity,DNA damage measurements, other telomeric factors,activation of factors. 2-Ovarian reserve and volumen 3- Oocytes collection 4- Quality of the embryos obtained. 5-Pregnancy results 6- Safety assessment |
1-Acumulación de telómeros cortos, actividad de la telomerasa, mediciones de daños en el ADN, otros factores teloméricos, activación de factores. 2- Reserva ovárica y volumen. 3- Número de ovocitos . 4- Calidad de los embriones obtenidos. 5-Resultado de embarazo. 6- Evaluación de la seguridad. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The evaluation will be done: 1-Accumulation of short telomeres,telomerase activity,DNA damage measurements, other telomeric factors,activation of factors. After V5 and V10 for women with low ovarian reserve and V5 and V8 for woman with normal ovarian reserve. 2-Ovarian reserve and volumen. V7 for women with low ovarian reserve and V4 for woman with normal ovarian reserve. 3- Oocytes collection.V8 for women with low ovarian reserve and V5 for woman with normal ovarian reserve. 4- Quality of the embryos obtained. V9 for women with low ovarian reserve and V6 for woman with normal ovarian reserve. 5-Pregnancy results. V10 and V11 for women with low ovarian reserve and V7 and V8 for woman with normal ovarian reserve. 6- Safety assessment, during all study. |
Tiempos de evaluación son: 1-Acumulación de telómeros cortos, actividad de la telomerasa, mediciones de daños en el ADN, otros factores teloméricos, activación de factores. Después V5 y V10 mujeres con baja reserva ovárica y V5 y V8 para mujeres con reserva ovárica normal. 2- Reserva ovárica y volumen. V7 mujeres con baja reserva ovárica y V4 para mujeres con reserva ovárica normal. 3- Número de ovocitos. V8 mujeres con baja reserva ovárica y V5 para mujeres con reserva ovárica normal. 4- Calidad de los embriones obtenidos. V9 mujeres con baja reserva ovárica y V6 para mujeres con reserva ovárica normal. 5-Resultado de embarazo. V10 and V11 mujeres con baja reserva ovárica y V7 and V8 para mujeres con reserva ovárica normal. 6- Evaluación de la seguridad. Durante todo el ensayo |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
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 | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Estudio piloto con evaluador ciego |
Pilot study with blind evaluator |
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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.8.5 | 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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LVLS |
Última visita del último paciente |
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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 | |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | |