A Phase 1/2 interventional study of 1000IU/day of Vitamine D and 5000IU/day of Vitamine D in Hematopoietic Stem Cell Transplantation, sponsored by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla. Completed at 7 sites in Spain. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2015-11-10.
Sponsored by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla · Phase 1/2, Interventional, and Prevention
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.
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.
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla is the lead sponsor of 119 studies on the registry; 26 are open to participants now.
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Exclusion Criteria:
Control group is composed by the first 50 patients included in the study. Those patients will not receive the treatment. Evaluations and follow-up will be the same as in the other groups.
It is composed by the following 50 patients joining the study. They will take 1000 IU of vitamin D once a day.
Drug: 1000IU/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.
Drug: 5000IU/day of Vitamine D
Administration of a specified dose of Vitamine D
Also known as: Vitamine D dose of 1000 international units (IU)
Administration of a specified dose of Vitamine D
Also known as: Vitamine D dose of 5000 international units (IU)
Incidence/severity of Graft-Versus-Host-Disease
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
Time frame: Day +150 post-transplant
Serum levels of Th1/Th2 cytokines
(IL-2, IL-4, IL-6, IL-10, tumor necrosis factor alfa (TNF)-α and interferon gamma (IFN-g)) are determined by flow cytometry using the BD Human Th1/Th2 Cytokine CBA
Time frame: Day -5 pre-transplant and +1, +7, +21,+56 and +100 post-transplant
Dendritic cells
The following markers were used to identify different subpopulations CD16-PB, CD45-V500, HLADR-FITC, BDCA-PE, CD11c-PerCP-Cy5.5, CD86-PE-Cy7, CD123-APC and CD14-APC-H7. Plasmacytoid dendritic cells: HLADR+ CD123++ CD11c- CD16- CD14- BDCA1- CD45+. Monocyte-derived dendritic cells: HLADR+ CD123+d CD11c+ CD16++ CD14-/+d BDCA- CD45+. Myeloid BDCA1 dendritic cells : HLADR+ CD123- CD11c+ CD16- CD14- BDCA+ CD45+
Time frame: Day +21,+56 and +100 post-transplant
Subpopulations of lymphocytes
To be identified using the combination CD19+CD8-FITC, CD3+CD56-PE, CD4- PerCP-Cy5.5, HLADR-APC T cells: CD3+ (CD3+CD4+CD8-, CD3+CD4-CD8+, CD3+CD4+CD8+, CD3+CD4-CD8+) B cells: CD19+ HLADR+ NK cells: CD3- CD19- CD56+ CD45RA-FITC and CCR7-PE were used to distinguish the repertory of naive/effector/memory of CD4 and CD8 cells. -naive T cells: CD45RA+CCR7+ -effector T cells: CD45RA+CCR7- -central memory T cells: CD45RA-CCR7+ -Peripheral memory T cells: CD45RA-CCR7-
Time frame: Day +21,+56 and +100 post-transplant
Regulatory T cells
after incubation of surface antigens (CD25-FITC, CD127-PE and CD4-PerCP-Cy5.5), cells were washed in PBS and then fixed and permeabilized with FoxP3 Staining Buffer Set (eBiosciences) for FOXP3 staining. phenotype of Treg: CD4+CD25+CD127-/+wFoxP3+
Time frame: Day +21,+56 and +100 post-transplant
NK markers
using the following combinations: CD94-FITC/CD56-PE/CD3-PerCP-Cy5.5/HLADR-APC CD11a-FITC/CD16-PE/CD3-PerCP-Cy5.5/CD56-APC CD158a-FITC/CD161-PE/CD3-PerCP-Cy5.5/CD56-APC CDNKB1-FITC/NKAT-PE/CD3-PerCP-Cy5.5/CD56-APC We identify NK cells with weak expression of CD56 (CD56 called " weak) and those expressing more intensely this marker CD56 "bright ". In addition the expression of different KIR receptor as CD158a , CD161 , and NKAT2 NKB1 were reported.
Time frame: Day +21,+56 and +100 post-transplant
Activation of T cells
Activation assays are performed on 500 µl of peripheral blood added in 48-well plates. Peripheral blood is stimulated or not with PMA (20µg/2ml) and ionomycin (0.91 µg/ml).
Time frame: Day +21,+56 and +100 post-transplant
Peak Plasma Concentration (Cmax) of Vitamin D
Peak Plasma Concentration (Cmax)
Time frame: Day -5 pre-transplant and +1, +7 and +21 post-transplant
Area under the plasma concentration of Vitamin D
Area under the plasma concentration versus time curve (AUC)
Time frame: Day -5 pre-transplant and +1, +7 and +21 post-transplant
Bone densitometry changes carried out by protocol in post-transplant period
Treatment effect in the subsequent development of osteoporosis
Time frame: Day +150 post-transplant
This study is completed, as verified in Nov 2015. You cannot join it, but the record below documents what was studied.
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Fundación Pública Andaluza para la gestión de la Investigación en Sevilla