Immunomodulatory Effect of Vitamin D in Allogenic Post-transplant

Hematopoietic Stem Cell Transplantation Clinical Trial

— Alovita-1  

Official title:

Immunomodulatory Effect of Vitamin D in Allogenic Post-transplant

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02600988
• Other study ID #: Alovita-1
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: June 9, 2015
• Last updated: November 5, 2015
• Start date: July 2011
• Est. completion date: April 2015

Study information

• Verified date: November 2015
• Source: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: April 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Hematopoietic Stem Cell Transplantation

Intervention

Drug:
• 1000IU/day of Vitamine D
Administration of a specified dose of Vitamine D
• 5000IU/day of Vitamine D
Administration of a specified dose of Vitamine D

Locations

Country	Name	City	State
Spain	Christelle Ferrà i Coll	Badalona	Barcelona
Spain	Carmen Martínez	Barcelona
Spain	David Valcárcel Ferreiras	Barcelona
Spain	Manuel Jurado Chacón	Granada
Spain	Raquel Saldaña Moreno	Jerez de la Frontera	Cádiz
Spain	Mª Ángeles Cuesta	Málaga
Spain	Fermín Martín Sánchez- Guijo	Salamanca

Sponsors (1)

Lead Sponsor	Collaborator
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Day +150 post-transplant	Yes
Secondary	Serum levels of Th1/Th2 cytokines	(IL-2, IL-4, IL-6, IL-10, tumor necrosis factor alfa (TNF)-a and interferon gamma (IFN-g)) are determined by flow cytometry using the BD Human Th1/Th2 Cytokine CBA	Day -5 pre-transplant and +1, +7, +21,+56 and +100 post-transplant	No
Secondary	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+	Day +21,+56 and +100 post-transplant	No
Secondary	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-	Day +21,+56 and +100 post-transplant	No
Secondary	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+	Day +21,+56 and +100 post-transplant	No
Secondary	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.	Day +21,+56 and +100 post-transplant	No
Secondary	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).	Day +21,+56 and +100 post-transplant	No
Secondary	Peak Plasma Concentration (Cmax) of Vitamin D	Peak Plasma Concentration (Cmax)	Day -5 pre-transplant and +1, +7 and +21 post-transplant	No
Secondary	Area under the plasma concentration of Vitamin D	Area under the plasma concentration versus time curve (AUC)	Day -5 pre-transplant and +1, +7 and +21 post-transplant	No
Secondary	Bone densitometry changes carried out by protocol in post-transplant period	Treatment effect in the subsequent development of osteoporosis	Day +150 post-transplant	Yes