Double-Blind Randomized Controlled Trial Evaluating the Efficacy of the Food Supplement Isitol® Versus Placebo on the Rate of Abnormal Sperm DNA Fragmentation
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- GYNOV
- 入组人数
- 72
- 试验地点
- 2
- 主要终点
- Change from baseline sperm DNA fragmentation rate at 4 months
研究概览
简要总结
In industrialised countries, it is estimated that about 15% of couples who wish to have a child are currently facing infertility problems, of which, in half of the cases, an anomaly in sperm quality or at least a factor of male origin is identified. The evaluation of sperm quality in males is based, for the most part, on the micro and macroscopic examination of various parameters (concentration, motility, physical abnormalities of the spermatozoa, etc.). Nevertheless, an increasing number of scientific studies have shown that the quality of sperm DNA, and in particular its fragmentation rate, is also associated with a lower fertilisation rate. The integrity of sperm DNA may be affected by an imbalance in the Red/Ox balance leading to uncompensated oxidative stress, and could be restored or improved by dietary hygiene measures and the consumption of specific dietary products. The ISITOL clinical study aims to evaluate the efficacy of a dietary supplement specifically formulated to target the various issues associated with male infertility, and in particular to contribute to the improvement of the sperm DNA fragmentation rate. The efficacy of the dietary supplement Isitol® (GYNOV SAS) on sperm DNA fragmentation rate and other secondary parameters is being evaluated through a single-centre, prospective, randomised, double-blind, interventional vs. placebo clinical study being conducted in France at Laboratoire Drouot (21 Rue Drouot - 75009 Paris - France) and led by Dr. Nino-Guy Cassuto. A total of 72 men aged between 20 and 45 years, with sperm DNA fragmentation rate ≥ 30% and with negative semen culture are recruited. The recruited patients were randomized in a 1:1 scheme into 2 groups (Isitol® treated vs placebo treated).
[Results to be reported later]
详细描述
Infertility is generally defined as a partner's failure to conceive after at least 12 months off contraception and is steadily increasing worldwide. In industrialised countries, it is estimated that around 15% of couples who wish to have a child are now facing it, and in half of the cases, an abnormality in sperm quality or at least a male factor is identified.
In males, the measurement of male fertility is mainly based on analyses that assess sperm quality macroscopically (spermiogram, spermocytogram) by evaluating the number, morphology, motility, presence of abnormalities, etc. These indicators are still considered to be the preferred indicators for assessing male fertility.
Nevertheless, since the mid-2000s, numerous in vitro and in vivo studies in humans and animals have shown that the integrity of sperm DNA, assessed by measuring the rate of DNA fragmentation and chromatin decondensation in spermatozoa, could be a relevant parameter in the etiology of male infertility. Furthermore, it has been observed that the rate of sperm DNA fragmentation is inversely correlated with pregnancy rate, success rate of assisted reproductive techniques and embryo quality.
The major identified cause of direct damage to DNA molecules and their possible fragmentation, but also to proteins and cell membranes in spermatozoa is oxidative stress. Unreduced Reactive oxygen species produced in the mitochondria-rich midpiece in excess are susceptible to damage the DNA in the sperm head. Several exogenous factors such as exposure to toxins, smoking, alcohol or unbalanced diet are also associated with promoting oxidative stress.
A fragmentation rate higher than 30% is considered high, it is indicative of altered chromatin and especially associated with a low probability of conceiving naturally or through in vitro techniques.
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
- Double (Participant, Care Provider)
盲法说明
The randomization scheme is 1 : 1 (treated with food supplement vs placebo). The different treatments (2) have been anonymized, a randomization list is used to assign an anonymous box number (5 random numbers) according to the patient's order of inclusion. Only the promoter is aware of the assignment of the randomization number with which treatment it corresponds.
入排标准
- 年龄范围
- 20 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Sperm DNA fragmentation rate ≥ 30 %
排除标准
- •Positive semen culture
结局指标
主要结局
Change from baseline sperm DNA fragmentation rate at 4 months
时间窗: Sperm DNA fragmentation rate is measured at first Visit (V0) and at the last Visit (V2) after 16 +/- 2 weeks of treatment with Isitol or placebo
Sperm DNA fragmentation rate is assessed by the TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) method. This method is based on the attachment of fluorochrome-coupled biotin-deoxyuridine (dUDP) complexes to the 3'OH ends of possible DNA fragments. The binding of the complexes to the DNA is catalysed by the enzyme Terminal-deoxynucleotidyltransferase. Spermatozoa with fragmented DNA are detected and their percentage measured directly by in-situ confocal fluorescence microscopy.
次要结局
- Change from baseline spermocytogram abnormalities count at 4 months(Spermocytogram abnormalities count is realised at first Visit (V0) and at the last Visit (V2) after 16 +/- 2 weeks of treatment with Isitol or placebo)
- Change from baseline semen pH at 4 months(Semen pH is measured at first Visit (V0) and at the last Visit (V2) after 16 +/- 2 weeks of treatment with Isitol or placebo)
- Change from baseline semen liquefaction time at 4 months(Semen liquefaction time is mesured at first Visit (V0) and at the last Visit (V2) after 16 +/- 2 weeks of treatment with Isitol or placebo)
- Change from baseline spermiogram total spermatozoa, round cells and polynuclear cells count at 4 months(Cells counts are realised at first Visit (V0) and at the last Visit (V2) after 16 +/- 2 weeks of treatment with Isitol or placebo)
- Change from baseline spermiogram viability and mobility count at 4 months(Viability and mobility are are evaluated at first Visit (V0) and at the last Visit (V2) after 16 +/- 2 weeks of treatment with Isitol or placebo)
- Change from baseline semen volume at 4 months(Semen volume is mesured at first Visit (V0) and at the last Visit (V2) after 16 +/- 2 weeks of treatment with Isitol or placebo)
- Change from baseline spermocytogram isolated flagella and of spermatozoa in cell lysis phase numbers at 4 months(Spermocytogram isolated flagella and of spermatozoa in cell lysis phase count is realised at first Visit (V0) and at the last Visit (V2) after 16 +/- 2 weeks of treatment with Isitol or placebo)
- Change from baseline sperm morphology scoring at 4 months(Sperm morphology scoring is realised at first Visit (V0) and at the last Visit (V2) after 16 +/- 2 weeks of treatment with Isitol or placebo)
- Change from baseline genes expression (AURKA, CCDC60, CCDC88B, CFAP46, HDAC4, CACNA1C, CACNA1H, CARHSP1, DNAH2, HMGB4, SPATA18) at 4 months(Genes expression measurement is realised at first Visit (V0) and at the last Visit (V2) after 16 +/- 2 weeks of treatment with Isitol or placebo)
- Change from baseline nuclear chromatin decondensation of spermatozoa at 4 months(Nuclear chromatin decondensation is measured at first Visit (V0) and at the last Visit (V2) after 16 +/- 2 weeks of treatment with Isitol or placebo)
- Change from baseline semen Red/ox potential at 4 months(Red/ox potential measurement is realised at first Visit (V0) and at the last Visit (V2) after 16 +/- 2 weeks of treatment with Isitol or placebo)