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Completed

NCT Number: NCT02600988

Immunomodulatory Effect of Vitamin D in Allogenic Post-transplant

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.

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Key information

Conditions

Hematopoietic Stem Cell Transplantation Graft vs Host Disease Immune System Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Christelle Ferrà i Coll, Badalona, Barcelona, Spain

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Treatment and study plan

1000IU/day of Vitamine D

Drug

Administration of a specified dose of Vitamine D

Other names: Vitamine D dose of 1000 international units (IU)

5000IU/day of Vitamine D

Drug

Administration of a specified dose of Vitamine D

Other names: Vitamine D dose of 5000 international units (IU)

Primary outcomes

  1. Incidence/severity of Graft-Versus-Host-Disease

    Time frame: 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

Secondary outcomes

  1. Serum levels of Th1/Th2 cytokines

    Time frame: Day -5 pre-transplant and +1, +7, +21,+56 and +100 post-transplant

    (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

  2. Dendritic cells

    Time frame: Day +21,+56 and +100 post-transplant

    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+

  3. Subpopulations of lymphocytes

    Time frame: Day +21,+56 and +100 post-transplant

    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-

  4. Regulatory T cells

    Time frame: Day +21,+56 and +100 post-transplant

    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+

  5. NK markers

    Time frame: Day +21,+56 and +100 post-transplant

    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.

  6. Activation of T cells

    Time frame: Day +21,+56 and +100 post-transplant

    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).

  7. Peak Plasma Concentration (Cmax) of Vitamin D

    Time frame: Day -5 pre-transplant and +1, +7 and +21 post-transplant

    Peak Plasma Concentration (Cmax)

  8. Area under the plasma concentration of Vitamin D

    Time frame: Day -5 pre-transplant and +1, +7 and +21 post-transplant

    Area under the plasma concentration versus time curve (AUC)

  9. Bone densitometry changes carried out by protocol in post-transplant period

    Time frame: Day +150 post-transplant

    Treatment effect in the subsequent development of osteoporosis

Sponsors and collaborators

Lead sponsor

Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

Other

Registry information

Acronym: Alovita-1

Important dates

Study start
2011
Primary completion
2015
Study completion
2015
First posted
Nov 10, 2015
Registry last updated
Nov 10, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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