<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/NCT04488237</url>
  </required_header>
  <id_info>
    <org_study_id>MTX side effects and VitD</org_study_id>
    <nct_id>NCT04488237</nct_id>
  </id_info>
  <brief_title>Vitamin D and Methotrexate Adverse Effects</brief_title>
  <official_title>Effect of Vitamin D Administration on Methotrexate Adverse Effects in Patients With Acute Lymphoblastic Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assiut University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assiut University</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>
      Since methotrexate toxicity represents a major problem in patients treating with cancer and&#xD;
      there are few studies about the role of vitamin D in the pathogenesis of this toxicity, so&#xD;
      the aim of the present study is investigation of the effect of vitamin D administration on&#xD;
      methotrexate toxicity such as oral ulcerations, bone marrow toxicity as well as renal and&#xD;
      hepatic toxicity also the role of inflammatory mediators and oxidative stress markers in&#xD;
      methotrexate toxicity will be evaluated, taking in consideration the dose of leucovorin&#xD;
      rescue.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Leukemia is a type of blood cancer that affects the body's white blood cells (WBCs). White&#xD;
      blood cells help fight infection and protect the body against disease, but in leukemia, some&#xD;
      of the white blood cells turn cancerous and don't work as they should. As more cancerous&#xD;
      cells form in the blood and bone marrow (spongy tissue inside the bones), there's less room&#xD;
      for healthy cells .&#xD;
&#xD;
      The different types of leukemia can be either acute (fast growing) or chronic (slow growing).&#xD;
      Acute lymphoblastic leukemia (ALL) happens when the body makes too many lymphoblasts (a type&#xD;
      of white blood cell). It's the most common type of childhood cancer.&#xD;
&#xD;
      Treatment outcome of acute leukemia has been improved recently using Methotrexate . Side&#xD;
      effects of methotrexate usually in the form of ulcerative stomatitis, leukopenia (lower&#xD;
      amount of white blood cells), nausea, abdominal discomfort, and elevated liver and kidney&#xD;
      function tests. Identifying risk factors leading to these side effects would be valuable to&#xD;
      develop preventive interventions and improve quality of life for these young patients.&#xD;
&#xD;
      Studies revealed a relationship between vitamin D deficiency and adverse reactions of&#xD;
      chemotherapy in cancer patients. This vitamin is important in many physiological processes in&#xD;
      the body as bone mineralization and immune regulations . A human body produces vitamin D as a&#xD;
      response to sun exposure. A person can also boost their vitamin D intake through certain&#xD;
      foods or supplements. .&#xD;
&#xD;
      Previous literature showed that receptors for vitamin D expressed in the mucosa and so there&#xD;
      is a relationship between vitamin D deficiency and increase inflammation and impairment of&#xD;
      mucosa .&#xD;
&#xD;
      Vitamin D is a fat-soluble vitamin that not only regulates calcium absorption and bone&#xD;
      metabolism, but can also regulate cell proliferation, differentiation and the immune&#xD;
      response, vitamin D insufficiency/deficiency is associated with poor clinical outcome and&#xD;
      significantly worse progression free survival of patients from leukemia and lymphoma.&#xD;
&#xD;
      Calcium is the most abundant element in the human body and is essential for life. It has a&#xD;
      key role in many physiological processes including skeletal mineralization, muscle&#xD;
      contraction, nerve impulse transmission, blood clotting, and hormone secretion . 1,&#xD;
      25-Dihydroxyvitamin D3 the active form of vitamin D plays major role in intestinal calcium&#xD;
      absorption, Calcium homeostasis is also regulated by parathyroid hormone.&#xD;
&#xD;
      Patients with acute lymphoblastic leukemia may be at risk of vitamin D deficiency because of&#xD;
      impaired vitamin intake and sunlight exposure .&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">September 2020</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Anticipated">September 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Effect of vitamin D administration on methotrexate adverse effects in patients with acute lymphoblastic leukemia</measure>
    <time_frame>1 to 2 years according to the availability of the cases</time_frame>
    <description>Since methotrexate toxicity represents a major problem in patients treating with cancer and there are few studies about the role of vitamin D in the pathogenesis of this toxicity, so the aim of the present study is investigation of the effect of vitamin D administration on methotrexate toxicity such as oral ulcerations, bone marrow toxicity as well as renal and hepatic toxicity also the role of inflammatory mediators and oxidative stress markers in methotrexate toxicity will be evaluated, taking in consideration the dose of leucovorin rescue.</description>
  </primary_outcome>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Acute Lymphoblastic Leukemia</condition>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vitamin D</intervention_name>
    <description>oral administration of Vitamin D in patients with acute leukemia treated with methotrexate</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        cases include patients with acute leumphoblastic leukemia recieving methotrexate in&#xD;
        treatment protocol&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with acute lymphoblastic leukemia who do not start treatment course with&#xD;
             methotrexate.&#xD;
&#xD;
          2. Both sex will be included.&#xD;
&#xD;
          3. Age group (1 -12 years)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with other type of cancer beside ALL.&#xD;
&#xD;
          2. Patients with renal, hepatic or hematological diseases.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>12 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mahmoud Hamdy Abdel-Raheem, Phd</last_name>
    <role>Study Director</role>
    <affiliation>Assiut University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Mohammed Mostafa Elbadr, Phd</last_name>
    <role>Study Director</role>
    <affiliation>Assiut University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Nivin Abdel-Azim Abdel-Rehim, Phd</last_name>
    <role>Study Director</role>
    <affiliation>Assiut University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Magy Ibrahim Anis Rizkallah, Bachelor</last_name>
    <phone>01282495775</phone>
    <phone_ext>002</phone_ext>
    <email>magy_rezkallah@med.aun.edu.eg</email>
  </overall_contact>
  <reference>
    <citation>Hunger SP, Lu X, Devidas M, Camitta BM, Gaynon PS, Winick NJ, Reaman GH, Carroll WL. Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the children's oncology group. J Clin Oncol. 2012 May 10;30(14):1663-9. doi: 10.1200/JCO.2011.37.8018. Epub 2012 Mar 12.</citation>
    <PMID>22412151</PMID>
  </reference>
  <reference>
    <citation>Anand A, Singh S, Sonkar AA, Husain N, Singh KR, Singh S, Kushwaha JK. Expression of vitamin D receptor and vitamin D status in patients with oral neoplasms and effect of vitamin D supplementation on quality of life in advanced cancer treatment. Contemp Oncol (Pozn). 2017;21(2):145-151. doi: 10.5114/wo.2017.68623. Epub 2017 Jun 30.</citation>
    <PMID>28947884</PMID>
  </reference>
  <reference>
    <citation>Oosterom N, Dirks NF, Heil SG, de Jonge R, Tissing WJE, Pieters R, van den Heuvel-Eibrink MM, Heijboer AC, Pluijm SMF. A decrease in vitamin D levels is associated with methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia. Support Care Cancer. 2019 Jan;27(1):183-190. doi: 10.1007/s00520-018-4312-0. Epub 2018 Jun 19.</citation>
    <PMID>29922939</PMID>
  </reference>
  <reference>
    <citation>Lalla RV, Choquette LE, Feinn RS, Zawistowski H, Latortue MC, Kelly ET, Baccaglini L. Multivitamin therapy for recurrent aphthous stomatitis: a randomized, double-masked, placebo-controlled trial. J Am Dent Assoc. 2012 Apr;143(4):370-6. doi: 10.14219/jada.archive.2012.0179.</citation>
    <PMID>22467697</PMID>
  </reference>
  <reference>
    <citation>Crew KD, Shane E, Cremers S, McMahon DJ, Irani D, Hershman DL. High prevalence of vitamin D deficiency despite supplementation in premenopausal women with breast cancer undergoing adjuvant chemotherapy. J Clin Oncol. 2009 May 1;27(13):2151-6. doi: 10.1200/JCO.2008.19.6162. Epub 2009 Apr 6.</citation>
    <PMID>19349547</PMID>
  </reference>
  <reference>
    <citation>Fakih MG, Trump DL, Johnson CS, Tian L, Muindi J, Sunga AY. Chemotherapy is linked to severe vitamin D deficiency in patients with colorectal cancer. Int J Colorectal Dis. 2009 Feb;24(2):219-24. doi: 10.1007/s00384-008-0593-y. Epub 2008 Oct 2.</citation>
    <PMID>18830610</PMID>
  </reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 23, 2020</study_first_submitted>
  <study_first_submitted_qc>July 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 27, 2020</study_first_posted>
  <last_update_submitted>July 23, 2020</last_update_submitted>
  <last_update_submitted_qc>July 23, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 27, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Assiut University</investigator_affiliation>
    <investigator_full_name>Magy Ibrahim Anis Rizkallah</investigator_full_name>
    <investigator_title>Demonstrator of cancer biology</investigator_title>
  </responsible_party>
  <keyword>methotrexate</keyword>
  <keyword>vitamin D</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Leukemia, Lymphoid</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin D</mesh_term>
  </intervention_browse>
  <!-- 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/NCT04488237
org study id: MTX side effects and VitD
nct id: NCT04488237
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Since methotrexate toxicity represents a major problem in patients treating with cancer and
      there are few studies about the role of vitamin D in the pathogenesis of this toxicity, so
      the aim of the present study is investigation of the effect of vitamin D administration on
      methotrexate toxicity such as oral ulcerations, bone marrow toxicity as well as renal and
      hepatic toxicity also the role of inflammatory mediators and oxidative stress markers in
      methotrexate toxicity will be evaluated, taking in consideration the dose of leucovorin
      rescue.
Leukemia is a type of blood cancer that affects the body's white blood cells (WBCs). White
      blood cells help fight infection and protect the body against disease, but in leukemia, some
      of the white blood cells turn cancerous and don't work as they should. As more cancerous
      cells form in the blood and bone marrow (spongy tissue inside the bones), there's less room
      for healthy cells .

      The different types of leukemia can be either acute (fast growing) or chronic (slow growing).
      Acute lymphoblastic leukemia (ALL) happens when the body makes too many lymphoblasts (a type
      of white blood cell). It's the most common type of childhood cancer.

      Treatment outcome of acute leukemia has been improved recently using Methotrexate . Side
      effects of methotrexate usually in the form of ulcerative stomatitis, leukopenia (lower
      amount of white blood cells), nausea, abdominal discomfort, and elevated liver and kidney
      function tests. Identifying risk factors leading to these side effects would be valuable to
      develop preventive interventions and improve quality of life for these young patients.

      Studies revealed a relationship between vitamin D deficiency and adverse reactions of
      chemotherapy in cancer patients. This vitamin is important in many physiological processes in
      the body as bone mineralization and immune regulations . A human body produces vitamin D as a
      response to sun exposure. A person can also boost their vitamin D intake through certain
      foods or supplements. .

      Previous literature showed that receptors for vitamin D expressed in the mucosa and so there
      is a relationship between vitamin D deficiency and increase inflammation and impairment of
      mucosa .

      Vitamin D is a fat-soluble vitamin that not only regulates calcium absorption and bone
      metabolism, but can also regulate cell proliferation, differentiation and the immune
      response, vitamin D insufficiency/deficiency is associated with poor clinical outcome and
      significantly worse progression free survival of patients from leukemia and lymphoma.

      Calcium is the most abundant element in the human body and is essential for life. It has a
      key role in many physiological processes including skeletal mineralization, muscle
      contraction, nerve impulse transmission, blood clotting, and hormone secretion . 1,
      25-Dihydroxyvitamin D3 the active form of vitamin D plays major role in intestinal calcium
      absorption, Calcium homeostasis is also regulated by parathyroid hormone.

      Patients with acute lymphoblastic leukemia may be at risk of vitamin D deficiency because of
      impaired vitamin intake and sunlight exposure .
observational model: Case-Control
time perspective: Prospective
measure: Effect of vitamin D administration on methotrexate adverse effects in patients with acute lymphoblastic leukemia
time frame: 1 to 2 years according to the availability of the cases
description: Since methotrexate toxicity represents a major problem in patients treating with cancer and there are few studies about the role of vitamin D in the pathogenesis of this toxicity, so the aim of the present study is investigation of the effect of vitamin D administration on methotrexate toxicity such as oral ulcerations, bone marrow toxicity as well as renal and hepatic toxicity also the role of inflammatory mediators and oxidative stress markers in methotrexate toxicity will be evaluated, taking in consideration the dose of leucovorin rescue.
intervention type: Drug
intervention name: Vitamin D
description: oral administration of Vitamin D in patients with acute leukemia treated with methotrexate
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 1 Year
maximum age: 12 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Mahmoud Hamdy Abdel-Raheem, Phd
role: Study Director
affiliation: Assiut University
last name: Mohammed Mostafa Elbadr, Phd
role: Study Director
affiliation: Assiut University
last name: Nivin Abdel-Azim Abdel-Rehim, Phd
role: Study Director
affiliation: Assiut University
last name: Magy Ibrahim Anis Rizkallah, Bachelor
phone: 01282495775
phone ext: 002
email: magy_rezkallah@med.aun.edu.eg
citation: Hunger SP, Lu X, Devidas M, Camitta BM, Gaynon PS, Winick NJ, Reaman GH, Carroll WL. Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the children's oncology group. J Clin Oncol. 2012 May 10;30(14):1663-9. doi: 10.1200/JCO.2011.37.8018. Epub 2012 Mar 12.
PMID: 22412151
citation: Anand A, Singh S, Sonkar AA, Husain N, Singh KR, Singh S, Kushwaha JK. Expression of vitamin D receptor and vitamin D status in patients with oral neoplasms and effect of vitamin D supplementation on quality of life in advanced cancer treatment. Contemp Oncol (Pozn). 2017;21(2):145-151. doi: 10.5114/wo.2017.68623. Epub 2017 Jun 30.
PMID: 28947884
citation: Oosterom N, Dirks NF, Heil SG, de Jonge R, Tissing WJE, Pieters R, van den Heuvel-Eibrink MM, Heijboer AC, Pluijm SMF. A decrease in vitamin D levels is associated with methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia. Support Care Cancer. 2019 Jan;27(1):183-190. doi: 10.1007/s00520-018-4312-0. Epub 2018 Jun 19.
PMID: 29922939
citation: Lalla RV, Choquette LE, Feinn RS, Zawistowski H, Latortue MC, Kelly ET, Baccaglini L. Multivitamin therapy for recurrent aphthous stomatitis: a randomized, double-masked, placebo-controlled trial. J Am Dent Assoc. 2012 Apr;143(4):370-6. doi: 10.14219/jada.archive.2012.0179.
PMID: 22467697
citation: Crew KD, Shane E, Cremers S, McMahon DJ, Irani D, Hershman DL. High prevalence of vitamin D deficiency despite supplementation in premenopausal women with breast cancer undergoing adjuvant chemotherapy. J Clin Oncol. 2009 May 1;27(13):2151-6. doi: 10.1200/JCO.2008.19.6162. Epub 2009 Apr 6.
PMID: 19349547
citation: Fakih MG, Trump DL, Johnson CS, Tian L, Muindi J, Sunga AY. Chemotherapy is linked to severe vitamin D deficiency in patients with colorectal cancer. Int J Colorectal Dis. 2009 Feb;24(2):219-24. doi: 10.1007/s00384-008-0593-y. Epub 2008 Oct 2.
PMID: 18830610
responsible party type: Principal Investigator
investigator affiliation: Assiut University
investigator full name: Magy Ibrahim Anis Rizkallah
investigator title: Demonstrator of cancer biology
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Lymphoid
mesh term: Vitamin D