Regulatory T-cell Induction by Low-dose Interleukin-2 in Women With Unexplained Repeated Spontaneous Early Miscarriages
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 3
- 主要终点
- Variation of rate of blood circulating T regulator lymphocytes(expressed in % of CD4 and total)
研究概览
简要总结
The purpose of this study is to demonstrate the ability of low dose IL-2 to stimulate peripheral blood Tregs of women with unexplained repeated early spontaneous miscarriages for development of a therapy to prevent fetal rejection by low dose IL-2.
详细描述
About 1 to 3% of women of childbearing age have repeated early spontaneous miscarriages that may be related to parental chromosomal abnormalities, uterine abnormalities, hormonal causes, infectious etiology, thrombophilia ... When one of these known causes is excluded, it is unexplained miscarriages of which half would be due to an immunological deregulation of the mother causing a decrease of the tolerance to the fetus.
In this context, the stimulation of regulatory T cells (Tregs) by low dose IL-2 is a therapeutic option with a rational, preclinical and clinical data very favorable.
In humans, low dose IL-2 allows preferential activation of Tregs and is very well tolerated. Several therapeutic trials have shown its efficiencies.
These elements make it possible to envisage the development of a therapeutic to prevent fetal rejection by IL2-fd on the women with spontaneous miscarriages by an immunological deregulation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Woman with at least 5 consecutive early miscarriages less than 14 weeks of amenorrhea and unexplained after the usual check-up;
- •Volunteer to participate in the trial and having given written consent after appropriate information.
排除标准
- •Uterine or pelvic abnormality: uterine malformation, intracavitary fibroid, synechiae, polyp, hydrosalpinx;
- •Balanced translocations in both spouses;
- •Diabetes type I or II;
- •Sickle cell disease;
- •Contraindication to pregnancy;
- •Constitutional or acquired thrombophilia (protein deficit C, S, ATIII, homozygous factor V or II deficiency, antiphospholipid syndrome, antithyroid antibodies positive, celiac disease, hyperhomocysteinemia);
- •Ovarian insufficiency (AMH <1 ng/ml); AFC < 4
- •Significant spermogram abnormalities and DNA fragmented more than 30%
- •Active HIV or HCV infection;
- •Main known contraindications to treatment with IL-2:
- •Hypersensitivity to the active substance or to any of the excipients;
- •Signs of progressive infection requiring antibiotic therapy;
- •History of organ allograft;
- •Pre-existing autoimmune disease;
- •Leukocytes <4000 / mm3; platelets <100,000 / mm3; hematocrit <30%;
- •hepatic or renal insufficiency;
- •depression;
- •significant history or existence of a serious heart disease (in doubtful cases, perform a stress test);
- •patients with autoimmune disease;
- •patients with an infection (septicemia, bacterial endocarditis, septic thrombophlebitis, peritonitis and pneumonia);
- •pregnancy;
- •Treatment with immunomodulators, immunosuppressants (class L04A of the ATC classification), in particular systemic corticosteroids, as well as aspirin and low molecular weight heparin;
- •No affiliation to a social security;
- •Person who has already been included in this study or in another at the same time;
- •Major incapacitated patient (tutorship / curatorship);
- •Patient with an allergy to taking IL2-fd;
- •Participants who would present professional risk factors (eg ionizing exposure);
研究组 & 干预措施
1
Low-dose IL-2
干预措施: low-dose IL-2 (Drug)
结局指标
主要结局
Variation of rate of blood circulating T regulator lymphocytes(expressed in % of CD4 and total)
时间窗: At the day 150 of Cycle 2 (each cycle is 28 days) compared from the day 10 of Cycle 11
Change of Tregs at Day 14 of cycles under low dose of IL-2 compared to the baseline of the first cycle without low dose of IL-2
次要结局
- Variation of rate of blood circulating T regulator lymphocytes(expressed in absolute numbers)(At the day 150 of Cycle 2 (each cycle is 28 days) compared from the day 10 of Cycle 11)