Effects of Telomerase Reactivation With Danazol in Ovarian Function.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Telomere length in granulosa cells
研究概览
简要总结
This project explores the implication of the telomere pathway in ovarian premature and regular aging. Telomere length and maintenance underlie several biological processes such cancer, aging, human diseases and the biology of stem cells. The reactivation of telomerase should lead to a rejuvenation of the ovarian tissue and the improvement of fertility.
The correlation of telomeric factors in blood and granulosa cells will be studied with the aim of finding telomeric biomarkers of ovarian aging.
详细描述
This is a pilot study, randomized, controled, blind, parallelo arm clinical trial with inactive substance and medicine.
A pilot study will be developed with a total of 45 individuals from 30 to 45 years old, who represent the most frequent population of women seeking for ART.
A control group composed of women with normal ovarian reserve (30 to 45 years old) is needed to compare telomeric and fertility parameters with the group of women with compromised ovarian reserve. Women in the control group irrespective of their age, will have a greater number of follicles compared to women belonging to the group with compromised ovarian reserve.
A group of women with diminished ovarian reserve that will take an inactive substance has been incluided to avoid biases and to set the fertility base line for women with compromised ovarian reserve. The use of an inactive substance or placebo will help obtain better quality results. For instance, if Danazol happened to improve the fertility outcome, then, there could be a possibility that the IVF improvement might be due to other components of the pill. Using placebo, this possibility would be eliminated, since the placebo will contain all components of the pill, except Danazol.
The development of a pilot study will help us understand the statisticl behavior or the telomeric factors as well as to determine the appropriate number of individuals that shoyuld be recruited in a clinical trial to have results with statistical significance. In addition, a pilot study will help us learn errors or undesired events that may happen during the clinical trial. For instance, if patients cannot follow the indications of their doctors and why, or what proportion of patients will drop the study and the reasons for it. Furthermore, it will also help us understand if there exist a tendency, an indication or even a clear beneficial effect for patients without harming them.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
During the first visist to the doctor, women will be selected according to the selection criteria. Those who seem to have a low ovarian reserve by ultrasound will be informed of the trial, and if they decide to participate, blood will be taken to analyze AMH values. On the second visit, women with low ovarian reserve will be randomized 1:1 for either inactive substance or Danazo, accordint to a computer-generated randomization list prepared by associated statistic. This way, the assigned group will be blind until the momento of executing the randomization procedure. Moment in which, the assigned group will be revealed.
Those with normal ovarian reserve will not be randomized and will just be included as controls.
To maintain the blinding of the trial, Danazol and placebo will be provided in boxs with blisters (PVC opaque and aluminium sealed).
Only the trial medication delegate(s) at the site will dispense the IMP and will know the treatment allocation.
入排标准
- 年龄范围
- 30 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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 decisión to use contraception methods different to sexual hormones, such as the use of condoms, during the treatment with Danazol.
- •In good general health as evidenced by medical history or diagnosed with body mass index between 18 and 30 kg/m
- •Women with normal (AMH valued must be equal or higher tan 2ng/ml) or compromised ovarian reserve (defined as AMH < 2 ng/ml)
- •Not having had any steroid hormones for one month.
排除标准
- •Pregnancy o 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 thromboembolicdiseases.
- •Known allergic reactions to components of the study product (cornstarch and lactose).
- •Having received ovulation induction drugs within one month before the inclusión 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 inclusión in the present study that could affect its objectives.
研究组 & 干预措施
CONTROL
A control group composed of women with normal ovarian reserve (30 to 45 yerras old) is needed to compare telomeric and fertility parameters with the group of women with compromised ovarian reserve. Note that the term "normal ovarian reserve" referred to older women indicates women that still have follicles in their ovaries -and thus, normal AMH values-, even though the number may be lower tan at a younger age or the quality of oocytes may be lower tan in younger women. In other words, women in the control group irrespective of their age, will have a greater number of follicles compared to women belonging to the group with compromised ovarian reserve.
干预措施: Without intervention (Other)
EXPERIMENTAL
A group of women with diminished ovarian reserve that will take an inactive substance has been included to avoik biases and to set the fertility base line for women with compromised ovarian reserve.
干预措施: Danazol/Placebo (Drug)
结局指标
主要结局
Telomere length in granulosa cells
时间窗: The evaluation of the main assessment criterion will be done both after eighth visit (36 hours post induction) for women with low ovarian reserve and fifth visit for woman with normal ovarian reserve
Measured in arbitrary units of fluorescence (a.u.) from 0 to 255 gray intensity (8bit) or Kb (continuous variable). Below 3 kb are considered critically short telomeres in humans.
次要结局
- Accumulation of short telomeres(Through study completion, an average of 1 year)
- DNA damage measurement(Through study completion, an average of 1 year)
- Telomerase activity(Through study completion, an average of 1 year)
- Other telomeric factors.(Through study completion, an average of 1 year)
研究者
Juan A Garcia-Velasco
PhD in Medicine and gynecology, University professor
IVI Madrid