<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/NCT01695148</url>
  </required_header>
  <id_info>
    <org_study_id>JHU IRB 4150</org_study_id>
    <nct_id>NCT01695148</nct_id>
  </id_info>
  <brief_title>Efficacy of β-carotene Biofortified Maize in Reducing Vitamin A Deficiency Among Children</brief_title>
  <official_title>Efficacy of β-carotene Biofortified Maize in Improving Vitamin A Status and Reducing the Prevalence of Vitamin A Deficiency Among Children in Rural Zambia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Johns Hopkins Bloomberg School of Public Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Food and Nutrition Commission, Zambia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Tropical Diseases Research Centre, Zambia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>HarvestPlus</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Canadian International Development Agency</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Zambia Agriculture Research Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Johns Hopkins Bloomberg School of Public Health</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this cluster-randomized trial is to examine whether daily consumption of&#xD;
      β-carotene biofortified maize flour can reduce the prevalence of vitamin A deficiency and&#xD;
      improve the vitamin A status and among 4-8 year old children in rural Zambia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Vitamin A deficiency is a major public health problem in Zambia, affecting approximately 40%&#xD;
      of young children. We aim to conduct a cluster-randomised controlled trial in the Mkushi&#xD;
      region of rural Zambia to test whether feeding children two daily meals containing β-carotene&#xD;
      biofortified maize flour compared to regular white maize flour-based meals for six months can&#xD;
      reduce the prevalence of vitamin A deficiency and improve the vitamin A status among 4-8 year&#xD;
      old children. Five hundred children in each arm will receive 2 meals a day, 6 days a week for&#xD;
      6 months, after which changes in serum retinol concentrations will be compared. An additional&#xD;
      arm of 250 children, enrolled from randomly sampled clusters, will not receive the maize&#xD;
      flour intervention but concurrently followed in order to evaluate overall effects of the&#xD;
      maize flour feeding scheme on measures of household food security.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">June 2013</completion_date>
  <primary_completion_date type="Actual">March 2013</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Increased Serum Retinol Concentration</measure>
    <time_frame>After 6 months of feeding</time_frame>
    <description>The investigators hypothesize a difference of 2.5 μg/dL or more in serum retinol among children receiving biofortified versus white maize flour-based meals. Serum retinol measures will be collected at baseline and at the end of 6 months and assessed by a High Performance Liquid Chromatography assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Decreased Prevalence of Vitamin A deficiency</measure>
    <time_frame>After 6 months of feeding</time_frame>
    <description>The investigators hypothesize a difference of 10% or more in the prevalence of vitamin A deficiency (i.e., serum retinol &lt; 0.7 μmol/l) among children consuming biofortified versus white maize flour-based meals, assuming a baseline prevalence of 40%.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Improved Dark Adaptation</measure>
    <time_frame>After 6 months of Feeding</time_frame>
    <description>The investigators hypothesize a difference in pupillary response to a light stimulus, as detected by dark adaptometry, in children receiving biofortified versus white maize flour-based meals.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">1228</enrollment>
  <condition>Vitamin A Deficiency</condition>
  <condition>Low Serum Retinol</condition>
  <arm_group>
    <arm_group_label>White Maize Flour</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Children will receive 2 meals a day (~200 g of white maize flour), 6 days a week for 6 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>β-Carotene Biofortified Maize</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Children will receive 2 meals a day (~200 g of beta-carotene biofortified maize flour), 6 days a week for 6 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Non-Intervened</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Children will receive no food for the duration of the study, but families in this group will receive an equivalent ration of food items at the end of the trial.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>β-Carotene Biofortified Maize Flour</intervention_name>
    <arm_group_label>β-Carotene Biofortified Maize</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>White Maize Flour</intervention_name>
    <arm_group_label>White Maize Flour</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Children 4-8 years of age&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>4 Years</minimum_age>
    <maximum_age>8 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Amanda C Palmer, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Johns Hopkins Bloomberg School of Public Health</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Rolf Klemm, DrPH</last_name>
    <role>Study Director</role>
    <affiliation>Johns Hopkins Bloomberg School of Public Health</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Kerry J Schulze, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Johns Hopkins Bloomberg School of Public Health</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Alain Labrique, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Johns Hopkins Bloomberg School of Public Health</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Parul Christian, DrPH</last_name>
    <role>Study Director</role>
    <affiliation>Johns Hopkins Bloomberg School of Public Health</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Sucheta Mehra, MS</last_name>
    <role>Study Director</role>
    <affiliation>Johns Hopkins Bloomberg School of Public Health</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Lee Shu-Fune Wu, MS</last_name>
    <role>Study Director</role>
    <affiliation>Johns Hopkins Bloomberg School of Public Health</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>JHU Office</name>
      <address>
        <city>Mkushi</city>
        <country>Zambia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Zambia</country>
  </location_countries>
  <reference>
    <citation>Howe JA, Tanumihardjo SA. Carotenoid-biofortified maize maintains adequate vitamin a status in Mongolian gerbils. J Nutr. 2006 Oct;136(10):2562-7. doi: 10.1093/jn/136.10.2562.</citation>
    <PMID>16988127</PMID>
  </reference>
  <reference>
    <citation>Howe JA, Tanumihardjo SA. Evaluation of analytical methods for carotenoid extraction from biofortified maize (Zea mays sp.). J Agric Food Chem. 2006 Oct 18;54(21):7992-7. doi: 10.1021/jf062256f.</citation>
    <PMID>17032000</PMID>
  </reference>
  <reference>
    <citation>Davis C, Jing H, Howe JA, Rocheford T, Tanumihardjo SA. beta-Cryptoxanthin from supplements or carotenoid-enhanced maize maintains liver vitamin A in Mongolian gerbils ( Meriones unguiculatus) better than or equal to beta-carotene supplements. Br J Nutr. 2008 Oct;100(4):786-93. doi: 10.1017/S0007114508944123. Epub 2008 Mar 3.</citation>
    <PMID>18312712</PMID>
  </reference>
  <reference>
    <citation>Davis CR, Howe JA, Rocheford TR, Tanumihardjo SA. The xanthophyll composition of biofortified maize (Zea mays Sp.) does not influence the bioefficacy of provitamin a carotenoids in Mongolian gerbils (Meriones unguiculatus). J Agric Food Chem. 2008 Aug 13;56(15):6745-50. doi: 10.1021/jf800816q. Epub 2008 Jul 11.</citation>
    <PMID>18616269</PMID>
  </reference>
  <reference>
    <citation>Muzhingi T, Gadaga TH, Siwela AH, Grusak MA, Russell RM, Tang G. Yellow maize with high beta-carotene is an effective source of vitamin A in healthy Zimbabwean men. Am J Clin Nutr. 2011 Aug;94(2):510-9. doi: 10.3945/ajcn.110.006486. Epub 2011 Jun 29.</citation>
    <PMID>21715509</PMID>
  </reference>
  <verification_date>February 2014</verification_date>
  <study_first_submitted>September 25, 2012</study_first_submitted>
  <study_first_submitted_qc>September 25, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 27, 2012</study_first_posted>
  <last_update_submitted>February 5, 2014</last_update_submitted>
  <last_update_submitted_qc>February 5, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 7, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Johns Hopkins Bloomberg School of Public Health</investigator_affiliation>
    <investigator_full_name>Keith P. West</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>beta-carotene biofortified maize</keyword>
  <keyword>micronutrients</keyword>
  <keyword>vitamin A</keyword>
  <keyword>serum retinol</keyword>
  <keyword>dark adaptation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Night Blindness</mesh_term>
    <mesh_term>Vitamin A Deficiency</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carotenoids</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/NCT01695148
org study id: JHU IRB 4150
nct id: NCT01695148
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The purpose of this cluster-randomized trial is to examine whether daily consumption of
      β-carotene biofortified maize flour can reduce the prevalence of vitamin A deficiency and
      improve the vitamin A status and among 4-8 year old children in rural Zambia.
Vitamin A deficiency is a major public health problem in Zambia, affecting approximately 40%
      of young children. We aim to conduct a cluster-randomised controlled trial in the Mkushi
      region of rural Zambia to test whether feeding children two daily meals containing β-carotene
      biofortified maize flour compared to regular white maize flour-based meals for six months can
      reduce the prevalence of vitamin A deficiency and improve the vitamin A status among 4-8 year
      old children. Five hundred children in each arm will receive 2 meals a day, 6 days a week for
      6 months, after which changes in serum retinol concentrations will be compared. An additional
      arm of 250 children, enrolled from randomly sampled clusters, will not receive the maize
      flour intervention but concurrently followed in order to evaluate overall effects of the
      maize flour feeding scheme on measures of household food security.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Increased Serum Retinol Concentration
time frame: After 6 months of feeding
description: The investigators hypothesize a difference of 2.5 μg/dL or more in serum retinol among children receiving biofortified versus white maize flour-based meals. Serum retinol measures will be collected at baseline and at the end of 6 months and assessed by a High Performance Liquid Chromatography assay.
measure: Decreased Prevalence of Vitamin A deficiency
time frame: After 6 months of feeding
description: The investigators hypothesize a difference of 10% or more in the prevalence of vitamin A deficiency (i.e., serum retinol < 0.7 μmol/l) among children consuming biofortified versus white maize flour-based meals, assuming a baseline prevalence of 40%.
measure: Improved Dark Adaptation
time frame: After 6 months of Feeding
description: The investigators hypothesize a difference in pupillary response to a light stimulus, as detected by dark adaptometry, in children receiving biofortified versus white maize flour-based meals.
arm group label: White Maize Flour
arm group type: Active Comparator
description: Children will receive 2 meals a day (~200 g of white maize flour), 6 days a week for 6 months.
arm group label: β-Carotene Biofortified Maize
arm group type: Experimental
description: Children will receive 2 meals a day (~200 g of beta-carotene biofortified maize flour), 6 days a week for 6 months.
arm group label: Non-Intervened
arm group type: No Intervention
description: Children will receive no food for the duration of the study, but families in this group will receive an equivalent ration of food items at the end of the trial.
intervention type: Dietary Supplement
intervention name: β-Carotene Biofortified Maize Flour
arm group label: β-Carotene Biofortified Maize
intervention type: Dietary Supplement
intervention name: White Maize Flour
arm group label: White Maize Flour
criteria: 
gender: All
minimum age: 4 Years
maximum age: 8 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Amanda C Palmer, PhD
role: Study Director
affiliation: Johns Hopkins Bloomberg School of Public Health
last name: Rolf Klemm, DrPH
role: Study Director
affiliation: Johns Hopkins Bloomberg School of Public Health
last name: Kerry J Schulze, PhD
role: Study Director
affiliation: Johns Hopkins Bloomberg School of Public Health
last name: Alain Labrique, PhD
role: Study Director
affiliation: Johns Hopkins Bloomberg School of Public Health
last name: Parul Christian, DrPH
role: Study Director
affiliation: Johns Hopkins Bloomberg School of Public Health
last name: Sucheta Mehra, MS
role: Study Director
affiliation: Johns Hopkins Bloomberg School of Public Health
last name: Lee Shu-Fune Wu, MS
role: Study Director
affiliation: Johns Hopkins Bloomberg School of Public Health
facility: 
country: Zambia
citation: Howe JA, Tanumihardjo SA. Carotenoid-biofortified maize maintains adequate vitamin a status in Mongolian gerbils. J Nutr. 2006 Oct;136(10):2562-7. doi: 10.1093/jn/136.10.2562.
PMID: 16988127
citation: Howe JA, Tanumihardjo SA. Evaluation of analytical methods for carotenoid extraction from biofortified maize (Zea mays sp.). J Agric Food Chem. 2006 Oct 18;54(21):7992-7. doi: 10.1021/jf062256f.
PMID: 17032000
citation: Davis C, Jing H, Howe JA, Rocheford T, Tanumihardjo SA. beta-Cryptoxanthin from supplements or carotenoid-enhanced maize maintains liver vitamin A in Mongolian gerbils ( Meriones unguiculatus) better than or equal to beta-carotene supplements. Br J Nutr. 2008 Oct;100(4):786-93. doi: 10.1017/S0007114508944123. Epub 2008 Mar 3.
PMID: 18312712
citation: Davis CR, Howe JA, Rocheford TR, Tanumihardjo SA. The xanthophyll composition of biofortified maize (Zea mays Sp.) does not influence the bioefficacy of provitamin a carotenoids in Mongolian gerbils (Meriones unguiculatus). J Agric Food Chem. 2008 Aug 13;56(15):6745-50. doi: 10.1021/jf800816q. Epub 2008 Jul 11.
PMID: 18616269
citation: Muzhingi T, Gadaga TH, Siwela AH, Grusak MA, Russell RM, Tang G. Yellow maize with high beta-carotene is an effective source of vitamin A in healthy Zimbabwean men. Am J Clin Nutr. 2011 Aug;94(2):510-9. doi: 10.3945/ajcn.110.006486. Epub 2011 Jun 29.
PMID: 21715509
responsible party type: Principal Investigator
investigator affiliation: Johns Hopkins Bloomberg School of Public Health
investigator full name: Keith P. West
investigator title: Professor
mesh term: Night Blindness
mesh term: Vitamin A Deficiency
mesh term: Carotenoids