Randomized Study of Vitamin A and D Prophylaxis Before Allogeneic Related and Unrelated Hematopoietic Stem Cell Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 220
- 试验地点
- 1
- 主要终点
- Cumulative incidence of gastrointestinal acute GVHD
研究概览
简要总结
The therapy under investigation is the addition of 300 000 IU of vitamin A and 100 000 IU of vitamin D before conditioning. The study will include patients with malignant diseases in hematologic response with indications for allogeneic transplantation with matched related or matched unrelated donor.
详细描述
Currently there is an emerging evidence of gut microbiota role in major complications of HCT, including GVHD, oral mucositis, infectious complications due to multi-drug resistant bacteria in the gut. Early exhaustion of most intestinal bacterial phyla after HSCT is documented in many studies. This effect of intensive anti-infectious therapy is well known. Most authors explain the disruption of intestinal microbiota by massive antibiotic treatment in order to prevent infectious complications due to immune deficiency following HCT. Early decrease in anaerobic bacteria (phylum Firmicutes) is revealed in many studies, with subsequent recovery of these bacterial populations within next 2 months. This time dynamics is in accordance with reported data on depletion of certain anaerobic gut bacteria, e.g., Ruminococcus, Faecalibacterium spp., Roseburia, Blautia post-transplant, being associated with severe complications in HCT patients. These results are in accordance with severe posttransplant dysbiosis at different mucosal sites post-HCT, as shown elsewhere by routine bacteriology techniques. The metabolism of bacteria with positive effect on GVHD includes both vitamin D and vitamin A. It was demonstrated that Ruminococcus abundance is dependent on vitamin A and D intake. Another bacteria genera Faecalibacterium prausnitzii, which is also reported to produce butyrate and reduce GVHD is also dependent on abundance of vitamin A. The big phylum Firmicutes are also dependant on vitamin D and their abundance is reported to be associated with lower incidence of immune complications and suppression of antibiotic-resistant strains. To summarize the idea of the study is based on modulation of gut microbiota, which in term may result in lower incidence of GVHD and toxic complications of HCT.
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis: acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, chronic myeloproliferative disease, chronic myeloid leukemia, lymphoblastic lymphoma, myeloma
- •Standard disease risk: less than 5% clonal blasts in the bone marrow and the absence of blast forms in the peripheral blood at the time of inclusion in the study or at least partial response for lymphoproliferative neoplasms.
- •Related compatible donor 10/10 HLA-matched or unrelated compatible donor 9-10/10 HLA-matched
- •Age ≥18 years
- •Absence of severe concomitant somatic diseases
排除标准
- •- Severe organ failure: creatinine more than 2 norms; ALT, AST more than 5 norms; bilirubin more than 1.5 normal;
- •respiratory failure more than 1 degree. or oxygen dependence
- •Unstable hemodynamics;
- •Uncontrolled bacterial or fungal infection at the time of inclusion, despite adequate antibacterial or antifungal therapy (CRP>70 mg/l at the time of inclusion).
- •Karnofsky index less than 70%
- •Repeated allogeneic transplantation of hematopoietic cells;
- •Creatinine clearance below 60ml/min/1.73m2;
- •Severe cardiac pathology, including a decrease in ejection fraction less than <50%, unstable angina, exertional angina of III-IV functional class, heart failure of III-IV functional class, arrhythmia grade V according to Lawn
- •Severe decrease in lung function, FEV1 <50% or DLCO<50% predicted
- •Pregnancy
- •Somatic or mental pathology that does not allow signing informed consent
研究组 & 干预措施
Vitamin supplementation
vitamin A 300 000 IU and vitamin D 100 000 IU on days -14 to -8 before transplantation
干预措施: Vitamin A (Drug)
Vitamin supplementation
vitamin A 300 000 IU and vitamin D 100 000 IU on days -14 to -8 before transplantation
干预措施: Vitamin D3 (Drug)
结局指标
主要结局
Cumulative incidence of gastrointestinal acute GVHD
时间窗: 125 days
Cumulative incidence of patients with acute GVHD II-IV grade, competing risk is death, relapse and primary graft failure
次要结局
- Incidence of HSCT-associated adverse events(125 days)
- Infectious complications(125 days)
- Event-free survival(2 years)
- Incidence of moderate and severe chronic GVHD(2 years)
- Non-relapse mortality analysis(2 years)
- Overall survival(2 years)
- GVHD-relapse-free survival analysis(2 years)
- Cumulative incidence of primary and secondary graft failure(125 days)
- Overall cumulative incidence of acute GVHD grade II-IV(125 days)
研究者
Ivan S Moiseev
Vice-director of RM Gorbacheva Research Institute
St. Petersburg State Pavlov Medical University