<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/NCT04435574</url>
  </required_header>
  <id_info>
    <org_study_id>70777</org_study_id>
    <nct_id>NCT04435574</nct_id>
  </id_info>
  <brief_title>Lactoferrin for Treatment of Iron Deficiency Anemia.</brief_title>
  <official_title>Comparison of Lactoferrin vs Traditional Iron Therapy for Treatment of Iron Deficiency Anemia in School-age Children.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cairo University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cairo 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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Anemia is a great public health problem affecting both developing and developed countries.&#xD;
      Iron deficiency anemia represents about 50% of causes of anemia worldwide.&#xD;
&#xD;
      Lactoferrin fortified milk has a positive effect on Hb and iron status of infants.&#xD;
&#xD;
      the hypothesis of this study is &quot;lactoferrin may have comparable efficacy to ferrous sulfate&#xD;
      therapy with more tolerability and fewer side effects&quot;.&#xD;
&#xD;
      the research question of this study is whether oral lactoferrin is effective for treatment of&#xD;
      iron deficiency anemia, compared to traditional ferrous sulfate therapy regarding hemoglobin&#xD;
      rise and side effects and tolerability.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Anemia is a great public health problem affecting both developing and developed countries. It&#xD;
      is considered the most prevalent form of malnutrition in children and adolescents.&#xD;
&#xD;
      Supplementation with standard iron therapy is the main treatment of iron deficiency anemia.&#xD;
&#xD;
      There are two types of iron that are available: ferric and ferrous iron but ferrous iron&#xD;
      better in absorption so it is more common in use.&#xD;
&#xD;
      Three types of ferrous iron are present: ferrous sulfate, ferrous fumarate, and ferrous&#xD;
      gluconate but all forms have annoying gastrointestinal side effects including diarrhea,&#xD;
      anorexia, heartburn, vomiting, nausea, abdominal cramps, upset stomach, and constipation&#xD;
      making continuation on it for many weeks unpleasant for all even adults.&#xD;
&#xD;
      Studies have been performed to explore the effect of oral bovine lactoferrin on iron&#xD;
      absorption on pregnant women. Many studies showed that oral bovine lactoferrin for pregnant&#xD;
      women increased levels of hemoglobin, total serum iron, and ferritin and decreased the&#xD;
      prevalence of iron deficiency anemia. although ferrous sulfate and lactoferrin both of them&#xD;
      significantly improve the body's iron stores to the same extent, gastrointestinal side&#xD;
      effects of lactoferrin were extremely lower than that of ferrous sulfate so oral bovine&#xD;
      lactoferrin can replace iron forms in the treatment of iron deficiency anemia in pregnancy.&#xD;
&#xD;
      Lactoferrin is a glycoprotein from the transferrin family consist of 691 amino acids. It is a&#xD;
      component of exocrine secretions such as milk and saliva and is present in neutrophil&#xD;
      granules. Lactoferrin was identified in 1939 in bovine milk and isolated in 1960 from both&#xD;
      human and bovine milk. Human colostrum shows the highest levels of lactoferrin while mature&#xD;
      milk and other secretions present lower.&#xD;
&#xD;
      Lactoferrin was used in children as antimicrobial in cases of acute diarrhea.In vitro data&#xD;
      document the growth inhibition of the diarrheal associated organisms: rotavirus, cholera,&#xD;
      salmonella, and shigella by human lactoferrin.&#xD;
&#xD;
      Studies about Milk formula fortified with bovine lactoferrin confirmed its positive effect on&#xD;
      Hb and iron status of infants. Recombinant human lactoferrin was extracted from rice seed, is&#xD;
      used by Ventria Bioscience as a dietary supplement for treatment of iron of deficiency&#xD;
      anemia.&#xD;
&#xD;
      Rationale:&#xD;
&#xD;
      Iron deficiency anemia has a high prevalence rate in scholar age children with their big need&#xD;
      to iron for anabolic processes of growth. Supplementation with standard iron therapy is the&#xD;
      main treatment however its unpleasant side effects negatively affect patient compliance.&#xD;
&#xD;
      Hypothesis:&#xD;
&#xD;
      Lactoferrin may have a positive effect in the treatment of iron deficiency anemia in&#xD;
      school-age children. Lactoferrin side effects less than standard iron therapy.&#xD;
&#xD;
      Research question:&#xD;
&#xD;
      Is lactoferrin usage in the treatment of iron deficiency anemia in scholar age children has a&#xD;
      positive effect and little side effects in comparison with standard iron therapy (ferrous&#xD;
      sulfate)?.&#xD;
&#xD;
      1. Objectives&#xD;
&#xD;
      This study aims to:&#xD;
&#xD;
        1. Evaluation of the effect of oral lactoferrin in the treatment of iron deficiency anemia&#xD;
           in school-age children in comparison with standard iron therapy (ferrous sulfate).&#xD;
&#xD;
        2. Assessment of side effects occurs with the usage of lactoferrin.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 5, 2018</start_date>
  <completion_date type="Actual">April 1, 2019</completion_date>
  <primary_completion_date type="Actual">April 1, 2019</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>the population for the study will be Scholar age Children attend family medicine clinic for treatment of iron deficiency anemia and their parents accept participation in the study.&#xD;
For confirmation of the diagnosis of iron deficiency anemia the following investigations will be done:&#xD;
CBC&#xD;
Serum total iron&#xD;
full medical history and examination will be performed. study participants will be assigned to either group A (lactoferrin group) or group B (ferrous sulfate group), and will receive the corresponding medication for 8 weeks.&#xD;
4 weeks follow up for side effects and hemoglobin level and 8 weeks follow up for side effects, hemoglobin level and serum iron will be performed.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Hemoglobin</measure>
    <time_frame>8 weeks</time_frame>
    <description>hemoglobin%</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Total serum iron</measure>
    <time_frame>8 weeks</time_frame>
    <description>Total serum iron</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Side effects profile</measure>
    <time_frame>4 weeks</time_frame>
    <description>Score of side effects</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">90</enrollment>
  <condition>Anemia, Iron Deficiency</condition>
  <arm_group>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>group A is lactoferrin group, receiving 100mg sachet of lactoferrin once daily.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group b</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>group B is the ferrous sulfate group, receiving 6mg/kg/ day single dose of ferrous sulfate.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lactoferrin</intervention_name>
    <description>Bovine Lactoferrin 100mg sachets.</description>
    <arm_group_label>Group A</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ferrous Sulfate</intervention_name>
    <description>6mg/kg of ferrous sulfate.</description>
    <arm_group_label>Group b</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Children with iron deficiency anemia.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Malabsorption diseases as coeliac disease.&#xD;
&#xD;
          -  Diseases causing chronic blood loss as Meckel diverticulum.&#xD;
&#xD;
          -  Documented history of allergy to lactoferrin or ferrous sulfate.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>12 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ghada Khfaji, Associate professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cairo University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Primary care center</name>
      <address>
        <city>Giza</city>
        <zip>12561</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <reference>
    <citation>Stoltzfus R. Defining iron-deficiency anemia in public health terms: a time for reflection. J Nutr. 2001 Feb;131(2S-2):565S-567S. doi: 10.1093/jn/131.2.565S.</citation>
    <PMID>11160589</PMID>
  </reference>
  <reference>
    <citation>Paesano R, Torcia F, Berlutti F, Pacifici E, Ebano V, Moscarini M, Valenti P. Oral administration of lactoferrin increases hemoglobin and total serum iron in pregnant women. Biochem Cell Biol. 2006 Jun;84(3):377-80. doi: 10.1139/o06-040.</citation>
    <PMID>16936810</PMID>
  </reference>
  <reference>
    <citation>Paesano R, Pietropaoli M, Gessani S, Valenti P. The influence of lactoferrin, orally administered, on systemic iron homeostasis in pregnant women suffering of iron deficiency and iron deficiency anaemia. Biochimie. 2009 Jan;91(1):44-51. doi: 10.1016/j.biochi.2008.06.004. Epub 2008 Jun 14.</citation>
    <PMID>18601971</PMID>
  </reference>
  <reference>
    <citation>Rezk M, Dawood R, Abo-Elnasr M, Al Halaby A, Marawan H. Lactoferrin versus ferrous sulphate for the treatment of iron deficiency anemia during pregnancy: a randomized clinical trial. J Matern Fetal Neonatal Med. 2016;29(9):1387-90. doi: 10.3109/14767058.2015.1049149. Epub 2015 Jun 3.</citation>
    <PMID>26037728</PMID>
  </reference>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>August 31, 2018</study_first_submitted>
  <study_first_submitted_qc>June 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 17, 2020</study_first_posted>
  <last_update_submitted>June 15, 2020</last_update_submitted>
  <last_update_submitted_qc>June 15, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 17, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Cairo University</investigator_affiliation>
    <investigator_full_name>Saeed Salah Abduljalil Soliman</investigator_full_name>
    <investigator_title>Lecturer of family medicine</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anemia</mesh_term>
    <mesh_term>Anemia, Iron-Deficiency</mesh_term>
    <mesh_term>Iron Deficiencies</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lactoferrin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04435574
org study id: 70777
nct id: NCT04435574
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Anemia is a great public health problem affecting both developing and developed countries.
      Iron deficiency anemia represents about 50% of causes of anemia worldwide.

      Lactoferrin fortified milk has a positive effect on Hb and iron status of infants.

      the hypothesis of this study is "lactoferrin may have comparable efficacy to ferrous sulfate
      therapy with more tolerability and fewer side effects".

      the research question of this study is whether oral lactoferrin is effective for treatment of
      iron deficiency anemia, compared to traditional ferrous sulfate therapy regarding hemoglobin
      rise and side effects and tolerability.
Anemia is a great public health problem affecting both developing and developed countries. It
      is considered the most prevalent form of malnutrition in children and adolescents.

      Supplementation with standard iron therapy is the main treatment of iron deficiency anemia.

      There are two types of iron that are available: ferric and ferrous iron but ferrous iron
      better in absorption so it is more common in use.

      Three types of ferrous iron are present: ferrous sulfate, ferrous fumarate, and ferrous
      gluconate but all forms have annoying gastrointestinal side effects including diarrhea,
      anorexia, heartburn, vomiting, nausea, abdominal cramps, upset stomach, and constipation
      making continuation on it for many weeks unpleasant for all even adults.

      Studies have been performed to explore the effect of oral bovine lactoferrin on iron
      absorption on pregnant women. Many studies showed that oral bovine lactoferrin for pregnant
      women increased levels of hemoglobin, total serum iron, and ferritin and decreased the
      prevalence of iron deficiency anemia. although ferrous sulfate and lactoferrin both of them
      significantly improve the body's iron stores to the same extent, gastrointestinal side
      effects of lactoferrin were extremely lower than that of ferrous sulfate so oral bovine
      lactoferrin can replace iron forms in the treatment of iron deficiency anemia in pregnancy.

      Lactoferrin is a glycoprotein from the transferrin family consist of 691 amino acids. It is a
      component of exocrine secretions such as milk and saliva and is present in neutrophil
      granules. Lactoferrin was identified in 1939 in bovine milk and isolated in 1960 from both
      human and bovine milk. Human colostrum shows the highest levels of lactoferrin while mature
      milk and other secretions present lower.

      Lactoferrin was used in children as antimicrobial in cases of acute diarrhea.In vitro data
      document the growth inhibition of the diarrheal associated organisms: rotavirus, cholera,
      salmonella, and shigella by human lactoferrin.

      Studies about Milk formula fortified with bovine lactoferrin confirmed its positive effect on
      Hb and iron status of infants. Recombinant human lactoferrin was extracted from rice seed, is
      used by Ventria Bioscience as a dietary supplement for treatment of iron of deficiency
      anemia.

      Rationale:

      Iron deficiency anemia has a high prevalence rate in scholar age children with their big need
      to iron for anabolic processes of growth. Supplementation with standard iron therapy is the
      main treatment however its unpleasant side effects negatively affect patient compliance.

      Hypothesis:

      Lactoferrin may have a positive effect in the treatment of iron deficiency anemia in
      school-age children. Lactoferrin side effects less than standard iron therapy.

      Research question:

      Is lactoferrin usage in the treatment of iron deficiency anemia in scholar age children has a
      positive effect and little side effects in comparison with standard iron therapy (ferrous
      sulfate)?.

      1. Objectives

      This study aims to:

        1. Evaluation of the effect of oral lactoferrin in the treatment of iron deficiency anemia
           in school-age children in comparison with standard iron therapy (ferrous sulfate).

        2. Assessment of side effects occurs with the usage of lactoferrin.
allocation: Randomized
intervention model: Single Group Assignment
intervention model description: the population for the study will be Scholar age Children attend family medicine clinic for treatment of iron deficiency anemia and their parents accept participation in the study.
For confirmation of the diagnosis of iron deficiency anemia the following investigations will be done:
CBC
Serum total iron
full medical history and examination will be performed. study participants will be assigned to either group A (lactoferrin group) or group B (ferrous sulfate group), and will receive the corresponding medication for 8 weeks.
4 weeks follow up for side effects and hemoglobin level and 8 weeks follow up for side effects, hemoglobin level and serum iron will be performed.
primary purpose: Treatment
masking: None (Open Label)
measure: Hemoglobin
time frame: 8 weeks
description: hemoglobin%
measure: Total serum iron
time frame: 8 weeks
description: Total serum iron
measure: Side effects profile
time frame: 4 weeks
description: Score of side effects
arm group label: Group A
arm group type: Experimental
description: group A is lactoferrin group, receiving 100mg sachet of lactoferrin once daily.
arm group label: Group b
arm group type: Active Comparator
description: group B is the ferrous sulfate group, receiving 6mg/kg/ day single dose of ferrous sulfate.
intervention type: Drug
intervention name: Lactoferrin
description: Bovine Lactoferrin 100mg sachets.
arm group label: Group A
intervention type: Drug
intervention name: Ferrous Sulfate
description: 6mg/kg of ferrous sulfate.
arm group label: Group b
criteria: 
gender: All
minimum age: 6 Years
maximum age: 12 Years
healthy volunteers: No
last name: Ghada Khfaji, Associate professor
role: Principal Investigator
affiliation: Cairo University
facility: 
country: Egypt
citation: Stoltzfus R. Defining iron-deficiency anemia in public health terms: a time for reflection. J Nutr. 2001 Feb;131(2S-2):565S-567S. doi: 10.1093/jn/131.2.565S.
PMID: 11160589
citation: Paesano R, Torcia F, Berlutti F, Pacifici E, Ebano V, Moscarini M, Valenti P. Oral administration of lactoferrin increases hemoglobin and total serum iron in pregnant women. Biochem Cell Biol. 2006 Jun;84(3):377-80. doi: 10.1139/o06-040.
PMID: 16936810
citation: Paesano R, Pietropaoli M, Gessani S, Valenti P. The influence of lactoferrin, orally administered, on systemic iron homeostasis in pregnant women suffering of iron deficiency and iron deficiency anaemia. Biochimie. 2009 Jan;91(1):44-51. doi: 10.1016/j.biochi.2008.06.004. Epub 2008 Jun 14.
PMID: 18601971
citation: Rezk M, Dawood R, Abo-Elnasr M, Al Halaby A, Marawan H. Lactoferrin versus ferrous sulphate for the treatment of iron deficiency anemia during pregnancy: a randomized clinical trial. J Matern Fetal Neonatal Med. 2016;29(9):1387-90. doi: 10.3109/14767058.2015.1049149. Epub 2015 Jun 3.
PMID: 26037728
responsible party type: Principal Investigator
investigator affiliation: Cairo University
investigator full name: Saeed Salah Abduljalil Soliman
investigator title: Lecturer of family medicine
mesh term: Anemia
mesh term: Anemia, Iron-Deficiency
mesh term: Iron Deficiencies
mesh term: Lactoferrin
sharing ipd: Undecided