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Immunomodulatory Effect of Vitamin D in Allogenic Post-transplant (Alovita-1)

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ClinicalTrials.gov Identifier: NCT02600988
Recruitment Status : Completed
First Posted : November 10, 2015
Last Update Posted : November 10, 2015
Sponsor:
Information provided by (Responsible Party):
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

Tracking Information
First Submitted Date  ICMJE June 9, 2015
First Posted Date  ICMJE November 10, 2015
Last Update Posted Date November 10, 2015
Study Start Date  ICMJE July 2011
Actual Primary Completion Date April 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 5, 2015)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: November 5, 2015)
  • 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
  • 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+
  • 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-
  • 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+
  • 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.
  • 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).
  • Peak Plasma Concentration (Cmax) of Vitamin D [ Time Frame: Day -5 pre-transplant and +1, +7 and +21 post-transplant ]
    Peak Plasma Concentration (Cmax)
  • 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)
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Immunomodulatory Effect of Vitamin D in Allogenic Post-transplant
Official Title  ICMJE Immunomodulatory Effect of Vitamin D in Allogenic Post-transplant
Brief Summary 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.
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Hematopoietic Stem Cell Transplantation
Intervention  ICMJE
  • Drug: 1000IU/day of Vitamine D
    Administration of a specified dose of Vitamine D
    Other Name: Vitamine D dose of 1000 international units (IU)
  • Drug: 5000IU/day of Vitamine D
    Administration of a specified dose of Vitamine D
    Other Name: Vitamine D dose of 5000 international units (IU)
Study Arms  ICMJE
  • No Intervention: Group 1: Control
    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.
  • Experimental: 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.
    Intervention: Drug: 1000IU/day of Vitamine D
  • Experimental: 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.
    Intervention: Drug: 5000IU/day of Vitamine D
Publications * Caballero-Velázquez T, Montero I, Sánchez-Guijo F, Parody R, Saldaña R, Valcarcel D, López-Godino O, Ferra I Coll C, Cuesta M, Carrillo-Vico A, Sánchez-Abarca LI, López-Corral L, Márquez-Malaver FJ, Pérez-Simón JA; GETH (Grupo Español de Trasplante Hematopoyético). Immunomodulatory Effect of Vitamin D after Allogeneic Stem Cell Transplantation: Results of a Prospective Multicenter Clinical Trial. Clin Cancer Res. 2016 Dec 1;22(23):5673-5681. Epub 2016 Jun 29.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 5, 2015)
150
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE April 2015
Actual Primary Completion Date April 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02600988
Other Study ID Numbers  ICMJE Alovita-1
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Study Sponsor  ICMJE Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: José Antonio Pérez-Simón, MD-PhD Head of haematology department
PRS Account Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Verification Date November 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP