Immunomodulatory Effect of Vitamin D in Allogenic Post-transplant
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 150
- 试验地点
- 7
- 主要终点
- Incidence/severity of Graft-Versus-Host-Disease
研究概览
简要总结
The purpose of this study is to determine whether vitamin D is effective in the prevention of graft-versus-host-disease after completion of allogeneic transplant.
详细描述
The allogeneic transplant of haematopoietic cell is the only treatment option for many malignant blood diseases. Unfortunately, the progression free survival and the quality of life of transplanted patients is limited due to the development of graft-versus-host-disease (GVHD).
The development of new prophylaxis strategies of GVHD based in the use of immunomodulator agents (allowing the generation of an immunotolerance state and avoiding the use of immunosuppression) is essential.
The GVHD is due to the cytotoxic effect of the donor lymphocytes T against healthy organs and tissues of the receptor. Calcineurin inhibitor combined with methotrexate or antibodies anti-lymphocytes T are used as standard prophylaxis. This type of antibodies has demonstrated efficacy to reduce GVHD, but have not increased survival due to increasing the risk of relapses and serious post-transplant infections.
Due to its interactions with VDR (vitamin D receptor) present in immune system cells, vitamin D is able to inhibit the activation of dendritic cells and the proliferation and production of cytokines by lymphocytes T. Based on this effect, the peri- and post- transplant administration of vitamin D might decrease the risk of GVHD in allogeneic transplanted patients, subsequently decreasing the immunosuppressant treatment requirements and improving the prognosis of those patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 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
- •Age ≥ 18 years
- •The patient should accomplish all the criteria to proceed to an allogeneic transplant
- •The patient or their legal guardians should signed the informed consent approved by the Ethics Committees of Clinical Trials
排除标准
- •Hypercalcemia ≥ 10.5 mg/dl
- •Renal insufficiency with creatinine level ≥ 2 x upper limit of normal (1,1 mg/dl)
- •Participation in others Clinical Trials in which the intervention may affect the result of the study.
- •Patients receiving GVHD immunoprophylaxis with thymoglobuline or GVHD prophylaxis including in vitro or in vivo lymphocytes T depletion (anti-lymphocyte T globulin, ALG)
- •Patients receiving a transplant from an haploidentical donor
研究组 & 干预措施
Group 2: 1000IU/day of Vitamine D
It is composed by the following 50 patients joining the study. They will take 1000 IU of vitamin D once a day.
干预措施: 1000IU/day of Vitamine D (Drug)
Group 3: 5000IU/day of Vitamine D
It is composed by the last 50 patients joining the study. They will take 5000 IU of vitamin D once a day.
干预措施: 5000IU/day of Vitamine D (Drug)
结局指标
主要结局
Incidence/severity of Graft-Versus-Host-Disease
时间窗: Day +150 post-transplant
Number of cases of GVHD/Seriousness graded according to National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease
次要结局
- Serum levels of Th1/Th2 cytokines(Day -5 pre-transplant and +1, +7, +21,+56 and +100 post-transplant)
- Dendritic cells(Day +21,+56 and +100 post-transplant)
- Subpopulations of lymphocytes(Day +21,+56 and +100 post-transplant)
- Regulatory T cells(Day +21,+56 and +100 post-transplant)
- NK markers(Day +21,+56 and +100 post-transplant)
- Activation of T cells(Day +21,+56 and +100 post-transplant)
- Peak Plasma Concentration (Cmax) of Vitamin D(Day -5 pre-transplant and +1, +7 and +21 post-transplant)
- Area under the plasma concentration of Vitamin D(Day -5 pre-transplant and +1, +7 and +21 post-transplant)
- Bone densitometry changes carried out by protocol in post-transplant period(Day +150 post-transplant)