<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03759262</url>
  </required_header>
  <id_info>
    <org_study_id>CHLA-18-00362</org_study_id>
    <nct_id>NCT03759262</nct_id>
  </id_info>
  <brief_title>Ultra-high Dose Vitamin D for HSCT</brief_title>
  <official_title>Pilot Study of Transplant-related Events in Patients Receiving Ultra-high-dose Vitamin D Supplementation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Children's Hospital Los Angeles</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Children's Hospital Los Angeles</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a pilot study to investigate the effects of achieving adequate vitamin D levels via&#xD;
      ultra-high-dose vitamin D supplementation given prior to hematopoietic stem cell transplant&#xD;
      on transplant-related complications and inflammatory biomarkers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Up to 70% of patients have vitamin D deficiency prior to hematopoietic stem cell transplant&#xD;
      (HSCT). Patients with sufficient Vitamin D levels (&gt;50nm/L) prior to allogeneic transplant&#xD;
      have significantly better overall survival (OS) and lower rates of rejection and relapse.&#xD;
      Vitamin D inhibits Th1 and augments Th2 cell development. Patients who receive vitamin D&#xD;
      supplementation during allogeneic transplant have less inflammatory-mediated processes such&#xD;
      as chronic graft versus host disease (GVHD) and lower levels of naïve CD8+ cells and CD40&#xD;
      ligand. Multiple studies have raised concern regarding the adequacy of standard and high-dose&#xD;
      vitamin D dosing for vitamin D deficiency. A single oral ultra-high dose of Vitamin D given&#xD;
      prior to HSCT has been shown to be a safe and well tolerated method of sustaining therapeutic&#xD;
      Vitamin D levels for 6-19 weeks.&#xD;
&#xD;
      This is a pilot study to investigate the dynamic changes in inflammatory biomarkers following&#xD;
      ultra-high-dose vitamin D supplementation. The study population is patients with total&#xD;
      vitamin D level &lt;/=50ng/mL prior to HSCT.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 10, 2018</start_date>
  <completion_date type="Actual">May 10, 2020</completion_date>
  <primary_completion_date type="Actual">May 10, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of graft-versus-host disease, veno-occlusive disease, and thrombotic microangiopathy</measure>
    <time_frame>100 days after transplant</time_frame>
    <description>Graft-versus-host disease, veno-occlusive disease, and thrombotic microangiopathy</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Vitamin D sufficiency following Stoss dosing</measure>
    <time_frame>prior to transplant</time_frame>
    <description>Vitamin D sufficiency following Stoss dosing prior to tranpslantation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rates of survival, relapse, and significant infections</measure>
    <time_frame>from time of transplant to 1 year after transplant</time_frame>
    <description>Clinically significant events including but not limited to survival, relapse, significant infections.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine levels</measure>
    <time_frame>before vitamin D is given, 1-2 weeks after vitamin D is given, day of transplant, day +7, day +14, and day +30</time_frame>
    <description>The investigators will examine changes in levels of IFN-gamma, TNF-alpha, IL-1a, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10 (in pg/mL) before and after vitamin D is given</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine stimulation test</measure>
    <time_frame>before vitamin D is given, and 1-2 weeks after vitamin D is given</time_frame>
    <description>The investigators will examine changes in the immune profile (reactivity of CD45, 235, 61, 66 197, 19, 4, 38, 163, 43, 7, 62L, 127, 123, 279, 274, 14, 90, 11c, 294, 15, 16, 25, 27, 8, 33, 3, 45RA, 56, 11b; pS6, p-p38, HLA-DR, pERK 1/2, pStat3, pStat1, TCRgd, pStat5) in response to cytokine stimulation before and after vitamin D is given</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">33</enrollment>
  <condition>Hematopoietic Stem Cell Transplant</condition>
  <arm_group>
    <arm_group_label>Vitamin D (Cholecalciferol)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All subjects will be enrolled to this arm. A single dose of ultra-high-dose vitamin D will be given.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cholecalciferol</intervention_name>
    <description>A single dose of ultra-high-dose vitamin D (cholecalciferol) will be given prior to hematopoietic stem cell transplant. Research labs including inflammatory biomarker panels will be obtained prior to and after the dose is given.</description>
    <arm_group_label>Vitamin D (Cholecalciferol)</arm_group_label>
    <other_name>vitamin D</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients who are preparing for HSCT&#xD;
&#xD;
          -  If a patient is receiving an autologous transplant, enrollment must occur prior to&#xD;
             first transplant in the case that the patient is planned for multiple transplants&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Uncorrected hypocalcemia or hypophosphatemia&#xD;
&#xD;
          -  Patients in the ICU or on renal replacement therapy&#xD;
&#xD;
          -  Patients who have had an allogeneic transplant within the past 12 months prior to&#xD;
             enrollment&#xD;
&#xD;
        Enrolled patients with 25OHD level ≤50 ng/mL continue on study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>0 Years</minimum_age>
    <maximum_age>25 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Etan Orgel, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Hospital Los Angeles</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Hospital Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90027</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Wallace G, Jodele S, Howell J, Myers KC, Teusink A, Zhao X, Setchell K, Holtzapfel C, Lane A, Taggart C, Laskin BL, Davies SM. Vitamin D Deficiency and Survival in Children after Hematopoietic Stem Cell Transplant. Biol Blood Marrow Transplant. 2015 Sep;21(9):1627-31. doi: 10.1016/j.bbmt.2015.06.009. Epub 2015 Jun 18.</citation>
    <PMID>26093045</PMID>
  </reference>
  <reference>
    <citation>Wallace G, Jodele S, Myers KC, Dandoy CE, El-Bietar J, Nelson A, Teusink-Cross A, Khandelwal P, Taggart C, Gordon CM, Davies SM, Howell JC. Single Ultra-High-Dose Cholecalciferol to Prevent Vitamin D Deficiency in Pediatric Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2018 Sep;24(9):1856-1860. doi: 10.1016/j.bbmt.2018.05.019. Epub 2018 May 18.</citation>
    <PMID>29782992</PMID>
  </reference>
  <reference>
    <citation>Hansson ME, Norlin AC, Omazic B, Wikstrom AC, Bergman P, Winiarski J, Remberger M, Sundin M. Vitamin d levels affect outcome in pediatric hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2014 Oct;20(10):1537-43. doi: 10.1016/j.bbmt.2014.05.030. Epub 2014 Jun 5.</citation>
    <PMID>24910378</PMID>
  </reference>
  <reference>
    <citation>Caballero-Velazquez T, Montero I, Sanchez-Guijo F, Parody R, Saldana R, Valcarcel D, Lopez-Godino O, Ferra I Coll C, Cuesta M, Carrillo-Vico A, Sanchez-Abarca LI, Lopez-Corral L, Marquez-Malaver FJ, Perez-Simon JA; GETH (Grupo Espanol de Trasplante Hematopoyetico). 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. doi: 10.1158/1078-0432.CCR-16-0238. Epub 2016 Jun 29.</citation>
    <PMID>27358490</PMID>
  </reference>
  <reference>
    <citation>van Etten E, Mathieu C. Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts. J Steroid Biochem Mol Biol. 2005 Oct;97(1-2):93-101. doi: 10.1016/j.jsbmb.2005.06.002. Epub 2005 Jul 19.</citation>
    <PMID>16046118</PMID>
  </reference>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>November 8, 2018</study_first_submitted>
  <study_first_submitted_qc>November 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 29, 2018</study_first_posted>
  <last_update_submitted>February 25, 2021</last_update_submitted>
  <last_update_submitted_qc>February 25, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 1, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>vitamin D</keyword>
  <keyword>cytokines</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin D</mesh_term>
    <mesh_term>Cholecalciferol</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03759262
org study id: CHLA-18-00362
nct id: NCT03759262
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a pilot study to investigate the effects of achieving adequate vitamin D levels via
      ultra-high-dose vitamin D supplementation given prior to hematopoietic stem cell transplant
      on transplant-related complications and inflammatory biomarkers.
Up to 70% of patients have vitamin D deficiency prior to hematopoietic stem cell transplant
      (HSCT). Patients with sufficient Vitamin D levels (>50nm/L) prior to allogeneic transplant
      have significantly better overall survival (OS) and lower rates of rejection and relapse.
      Vitamin D inhibits Th1 and augments Th2 cell development. Patients who receive vitamin D
      supplementation during allogeneic transplant have less inflammatory-mediated processes such
      as chronic graft versus host disease (GVHD) and lower levels of naïve CD8+ cells and CD40
      ligand. Multiple studies have raised concern regarding the adequacy of standard and high-dose
      vitamin D dosing for vitamin D deficiency. A single oral ultra-high dose of Vitamin D given
      prior to HSCT has been shown to be a safe and well tolerated method of sustaining therapeutic
      Vitamin D levels for 6-19 weeks.

      This is a pilot study to investigate the dynamic changes in inflammatory biomarkers following
      ultra-high-dose vitamin D supplementation. The study population is patients with total
      vitamin D level </=50ng/mL prior to HSCT.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: Incidence of graft-versus-host disease, veno-occlusive disease, and thrombotic microangiopathy
time frame: 100 days after transplant
description: Graft-versus-host disease, veno-occlusive disease, and thrombotic microangiopathy
measure: Vitamin D sufficiency following Stoss dosing
time frame: prior to transplant
description: Vitamin D sufficiency following Stoss dosing prior to tranpslantation
measure: Rates of survival, relapse, and significant infections
time frame: from time of transplant to 1 year after transplant
description: Clinically significant events including but not limited to survival, relapse, significant infections.
measure: Cytokine levels
time frame: before vitamin D is given, 1-2 weeks after vitamin D is given, day of transplant, day +7, day +14, and day +30
description: The investigators will examine changes in levels of IFN-gamma, TNF-alpha, IL-1a, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10 (in pg/mL) before and after vitamin D is given
measure: Cytokine stimulation test
time frame: before vitamin D is given, and 1-2 weeks after vitamin D is given
description: The investigators will examine changes in the immune profile (reactivity of CD45, 235, 61, 66 197, 19, 4, 38, 163, 43, 7, 62L, 127, 123, 279, 274, 14, 90, 11c, 294, 15, 16, 25, 27, 8, 33, 3, 45RA, 56, 11b; pS6, p-p38, HLA-DR, pERK 1/2, pStat3, pStat1, TCRgd, pStat5) in response to cytokine stimulation before and after vitamin D is given
arm group label: Vitamin D (Cholecalciferol)
arm group type: Experimental
description: All subjects will be enrolled to this arm. A single dose of ultra-high-dose vitamin D will be given.
intervention type: Drug
intervention name: Cholecalciferol
description: A single dose of ultra-high-dose vitamin D (cholecalciferol) will be given prior to hematopoietic stem cell transplant. Research labs including inflammatory biomarker panels will be obtained prior to and after the dose is given.
arm group label: Vitamin D (Cholecalciferol)
other name: vitamin D
criteria: 
gender: All
minimum age: 0 Years
maximum age: 25 Years
healthy volunteers: No
last name: Etan Orgel, MD
role: Principal Investigator
affiliation: Children's Hospital Los Angeles
facility: 
country: United States
citation: Wallace G, Jodele S, Howell J, Myers KC, Teusink A, Zhao X, Setchell K, Holtzapfel C, Lane A, Taggart C, Laskin BL, Davies SM. Vitamin D Deficiency and Survival in Children after Hematopoietic Stem Cell Transplant. Biol Blood Marrow Transplant. 2015 Sep;21(9):1627-31. doi: 10.1016/j.bbmt.2015.06.009. Epub 2015 Jun 18.
PMID: 26093045
citation: Wallace G, Jodele S, Myers KC, Dandoy CE, El-Bietar J, Nelson A, Teusink-Cross A, Khandelwal P, Taggart C, Gordon CM, Davies SM, Howell JC. Single Ultra-High-Dose Cholecalciferol to Prevent Vitamin D Deficiency in Pediatric Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2018 Sep;24(9):1856-1860. doi: 10.1016/j.bbmt.2018.05.019. Epub 2018 May 18.
PMID: 29782992
citation: Hansson ME, Norlin AC, Omazic B, Wikstrom AC, Bergman P, Winiarski J, Remberger M, Sundin M. Vitamin d levels affect outcome in pediatric hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2014 Oct;20(10):1537-43. doi: 10.1016/j.bbmt.2014.05.030. Epub 2014 Jun 5.
PMID: 24910378
citation: Caballero-Velazquez T, Montero I, Sanchez-Guijo F, Parody R, Saldana R, Valcarcel D, Lopez-Godino O, Ferra I Coll C, Cuesta M, Carrillo-Vico A, Sanchez-Abarca LI, Lopez-Corral L, Marquez-Malaver FJ, Perez-Simon JA; GETH (Grupo Espanol de Trasplante Hematopoyetico). 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. doi: 10.1158/1078-0432.CCR-16-0238. Epub 2016 Jun 29.
PMID: 27358490
citation: van Etten E, Mathieu C. Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts. J Steroid Biochem Mol Biol. 2005 Oct;97(1-2):93-101. doi: 10.1016/j.jsbmb.2005.06.002. Epub 2005 Jul 19.
PMID: 16046118
responsible party type: Sponsor
mesh term: Vitamin D
mesh term: Cholecalciferol
sharing ipd: No