Effects of Immunomodulatory Therapy on Gonadal Function in Women With Autoimmune Premature Ovarian Insufficiency
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Number of antral follicles in response to ovarian stimulation 4 months after last rituximab infusion.
研究概览
简要总结
Title: Effects of immunomodulatory therapy on gonadal function in women with autoimmune premature ovarian insufficiency (POI)
Trial objectives and purpose: To study if rituximab therapy can improve ovarian response to gonadotropin stimulation and menstrual function in women with autoimmune POI.
Treatment: Controlled ovarian hyperstimulation before and four months after an infusion of 1-gram rituximab (Mabthera®) twice with two weeks interval. Follow-up period 12 months after infusion.
Primary outcome: Number of antral follicles and the size of the largest follicle in response to ovarian stimulation.
Secondary outcomes:
- Reestablishment of spontaneous menstrual bleedings during the 12 months' study period
- Ovulation during the 12 months' study period
- Change in B-cell count, autoantibody indices and immunoglobulin levels (IgG) after treatment
Safety outcomes: All adverse events. Of particular relevance are any hospital admissions, infections and allergic reactions.
Study population: Fifteen women with autoimmune POI defined as absence of menstruation > 6 months and elevated serum level of follicle stimulation hormone > 40 International units (IU)/L.
Inclusion criteria: Autoimmune POI defined as presence of autoantibodies against 21-hydroxylase (OH), side chain cleavage enzyme (SCC), 17-OH and/or neuronal apoptosis inhibitory protein (NACHT) leucine-rich-repeat protein 5 (NALP5) or other relevant autoantibodies; 18-35 yrs of age; body mass index 19-30.
Exclusion criteria: Hypersensitivity to rituximab; severe infection; severe immunosuppression; cardiac disease; cancer; benign tumours of the hypothalamus, pituitary, or ovary; ovarian enlargement or ovarian cyst; vaginal bleeding of unknown aetiology.
Time plan: The study is expected to start the spring 2017. It is expected to be closed spring 2023.
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 35 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Autoimmune premature ovarian insufficiency defined as presence of autoantibodies against 21-OH, SCC, 17-OH and/or NALP5 or other relevant autoantibodies
- •18-35 yrs of age
- •Body mass index 19-
- •In fertile females, willingness to comply with effective contraceptive methods.
- •Ability to provide informed consent
排除标准
- •Documented hypersensitivity or intolerance to rituximab
- •Active, severe infection
- •Severe immunosuppression
- •Severe cardiac disease
- •Benign tumours of the hypothalamus, pituitary, or ovary; ovarian enlargement or ovarian cyst
- •Vaginal bleeding of unknown aetiology
- •Hormone replacement therapy (HRT) within four weeks prior study entry.
- •Pregnant or lactating women
- •Concurrent treatment with other immunosuppressive drugs
- •Vaccination within 4 weeks of infusion of study medication
- •Severe psychiatric disorder
- •Patient with any condition or any circumstance that in the opinion of the investigator would make it unsafe to undergo treatment with Rituximab.
研究组 & 干预措施
rituximab
Controlled ovarian hyperstimulation will be performed before and four months after two infusions of 1-gram rituximab (Mabthera®).
干预措施: Rituximab (Drug)
结局指标
主要结局
Number of antral follicles in response to ovarian stimulation 4 months after last rituximab infusion.
时间窗: 4 months
Vaginal ultrasound measurement
The largest follicle in response to ovarian stimulation 4 months after last rituximab infusion.
时间窗: 4 months
Vaginal ultrasound measurement
次要结局
- Spontaneous menstrual bleedings during the 12 months' study period(12 months)
- Ovulation during the 12 months' study period(12 months)
- Immunoglobulin levels(4 and 12 months)
研究者
Angelica Lindén Hirschberg
Professor
Karolinska University Hospital