<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/NCT03012048</url>
  </required_header>
  <id_info>
    <org_study_id>IRB-HSR 18662</org_study_id>
    <nct_id>NCT03012048</nct_id>
  </id_info>
  <brief_title>Effectiveness of Point-of-use Water Treatment Technologies to Prevent Stunting Among Children in South Africa</brief_title>
  <official_title>Effectiveness of Low-cost Point-of-use Water Treatment Technologies to Prevent Stunting Among Children in Limpopo, South Africa</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Virginia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Venda</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Virginia</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This project is a community-based randomized controlled trial designed to test the&#xD;
      effectiveness of two point-of-use water treatment technologies to improve clean drinking&#xD;
      water access, reduce enteropathogen burden, and improve child growth among children in&#xD;
      Limpopo, South Africa.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Lack of access to safe water in low-resource settings likely contributes to stunted growth&#xD;
      early in life, which affects more than a quarter of children under 5 years worldwide.&#xD;
      Point-of-use water treatment technologies have the potential to provide effective and&#xD;
      low-cost solutions to improving quality of drinking water in these settings. One such&#xD;
      technology, a silver-impregnated ceramic disk, continually disinfects water in household&#xD;
      water storage containers by diffusing silver into the water for daily treatment of 10 to 15&#xD;
      liters for at least six months. Silver-impregnated ceramic water filters are another&#xD;
      commercially available technology that additionally remove pathogens mechanically. While both&#xD;
      technologies have proven to be highly effective in treating water, it is unknown whether the&#xD;
      use of these technologies will translate to improvements in child health outcomes. This&#xD;
      community-based intervention trial will estimate the effect of the silver-impregnated ceramic&#xD;
      disk and a silver-impregnated ceramic water filter on linear growth of children in Limpopo,&#xD;
      South Africa.&#xD;
&#xD;
      Households in the Dzimauli community will be randomized to receive the ceramic disk, a water&#xD;
      filter, the safe-storage water container alone, or no intervention. Children will be followed&#xD;
      every three months for 2 years to assess height, weight, and pathogen burden in stool&#xD;
      samples. Cognitive assessments will be completed at 2, 5, and 7 years of follow-up. The&#xD;
      investigators hypothesize that children in households given the ceramic disk or the water&#xD;
      filter will show improved linear growth compared to those in households without these&#xD;
      interventions. The investigators expect that the ceramic disk will perform similarly to the&#xD;
      water filter and result in similar improvements in linear growth when compared to children&#xD;
      from control households.&#xD;
&#xD;
      Estimates of effectiveness demonstrated in this trial will provide the necessary evidence&#xD;
      base to support the scale-up of manufacturing and distribution of the ceramic disks and&#xD;
      filters, which could provide a robust point-of-use water treatment solution for rural areas.&#xD;
      By helping to identify effective tools to reduce the risk of stunting in children, the trial&#xD;
      will contribute to targets to improve child health in low-resource settings.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">June 2016</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2018</primary_completion_date>
  <phase>N/A</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>Change in height-for-age z-score (ΔHAZ)</measure>
    <time_frame>From 0-2 years of follow-up</time_frame>
    <description>Height measured quarterly among all children under age 15 in the households, z-scores calculated from WHO growth standards</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in weight-for-age z-score (ΔWAZ)</measure>
    <time_frame>From 0-2 years of follow-up</time_frame>
    <description>Weight measured quarterly among all children under age 15 in the households, z-scores calculated from WHO growth standards</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pathogen burden in stool samples</measure>
    <time_frame>Quarterly from 0-2 years of follow-up</time_frame>
    <description>Non-diarrheal stools collected from the youngest child under 3 years of age in each household; testing for EAEC, EHEC/EPEC, ETEC, Shigella/EIEC, Giardia, Campylobacter, Cryptosporidium, Adenovirus by qPCR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prevalence of diarrhea</measure>
    <time_frame>Quarterly from 0-2 years of follow-up</time_frame>
    <description>7-day recall of diarrhea in the youngest child under 3 years of age in each household</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive function - Bayley Scales of Infant Development III (ages 2-3); Wechsler Preschool and Primary Scale of Intelligence III (ages 3-6); Raven's Combined Matrices (ages &gt; 6)</measure>
    <time_frame>2, 5, and 7 years of follow-up</time_frame>
    <description>Cognitive assessments will be completed for the youngest child in each household (determined at enrollment) using age-appropriate developmental tests that have already been adapted, translated, and piloted in this population. Caregivers will be asked to bring their child to the local health clinic to be assessed by a Psychological Research Assistant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Silver levels in treated water samples</measure>
    <time_frame>Quarterly from 0-2 years of follow-up</time_frame>
    <description>Treated water samples will be taken from a random subset of 50 households receiving the filter or ceramic disk every three months to determine the silver levels in treated water from the households. Total silver concentration will be measured by graphite furnace atomic absorption spectrometry (U.S.E.P.A. Method 7010).</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">415</enrollment>
  <condition>Diarrhoea;Infectious;Presumed</condition>
  <condition>Diarrhea, Infantile</condition>
  <condition>Diarrhea Tropical</condition>
  <condition>Environmental Exposure</condition>
  <condition>Enteropathy</condition>
  <condition>Malnutrition, Child</condition>
  <arm_group>
    <arm_group_label>MadiDrop (ceramic tablet)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Households receive a MadiDrop (silver-impregnated ceramic tablet) in a safe-storage water container to use for all drinking water needs in the household. MadiDrops are replaced every 6 months over the 2-year intervention study period.&#xD;
In July 2017, all households in the MadiDrop arm were crossed over to the ceramic water filter arm due to inconsistent silver release from the ceramic tablets.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Silver-impregnated ceramic water filter</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Households receive a silver-impregnated ceramic filter in a safe-storage water container to use for all drinking water needs in the household. Filters are replaced at the end of the 2-year intervention study period.&#xD;
In December 2017, all silver-impregnated ceramic water filters were replaced with the same ceramic filters without silver due to continued inconsistencies with silver release.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Safe-storage water container</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Households receive a safe-storage water container alone to use for all drinking water needs in the household.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No intervention</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Households are encouraged to continue their usual water treatment practices.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Silver-impregnated ceramic tablet</intervention_name>
    <description>A silver-impregnated ceramic disk used for drinking water treatment that was developed by engineers at the University of Virginia. When the ceramic disk is placed in a household water storage container, silver diffuses through the porous ceramic into the water at a release rate that is effective for continual disinfection of waterborne pathogens while remaining below the silver drinking water standard. The disk is effective for daily treatment of 10 to 15 liters for at least six months.&#xD;
This intervention was removed from the study in July 2017 (approximately at 1 year of follow-up).</description>
    <arm_group_label>MadiDrop (ceramic tablet)</arm_group_label>
    <other_name>MadiDrop (trade name)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Silver-impregnated ceramic water filter</intervention_name>
    <description>Silver-impregnated ceramic water filter are well-developed, tested, and widely-used devices. In addition to mechanically removing pathogens, the filter is treated with silver to reduce live pathogens that pass through the filter and to provide residual disinfectant to reduce risk of recontamination after treatment.&#xD;
This intervention was replaced with ceramic filters without silver in Dec 2017 (approximately at 1.5 years of follow-up).</description>
    <arm_group_label>Silver-impregnated ceramic water filter</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Safe-storage water container</intervention_name>
    <description>The safe-storage water containers used in this study are plastic buckets with a spigot, purchased locally.</description>
    <arm_group_label>Safe-storage water container</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Mother is in third trimester of pregnancy or there is at least one child under 3 years&#xD;
             of age in the household&#xD;
&#xD;
          -  The child's caregiver is at least 16 years of age&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  The household has chlorinated water piped into the home or routinely delivered (via&#xD;
             truck or diversion) to a permanent, engineered system that stores the water within the&#xD;
             property&#xD;
&#xD;
          -  The household currently uses a ceramic filter or other commercial water treatment&#xD;
             technology (including a permanent, engineered system that treats the water through&#xD;
             filtration and/or chlorination)&#xD;
&#xD;
          -  The household has plans to move outside the community in the next 6 months&#xD;
&#xD;
          -  The youngest child under 3 years of age is seriously ill (has a severe disease&#xD;
             requiring prolonged hospitalization or a severe or chronic condition diagnosed by&#xD;
             medical doctor, e.g. neonatal disease, renal disease, chronic heart failure, liver&#xD;
             disease, cystic fibrosis, congenital conditions)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pascal O Bessong, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Venda, Limpopo, South Africa</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Rebecca Dillingham, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Virginia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Venda</name>
      <address>
        <city>Thohoyandou</city>
        <state>Limpopo</state>
        <zip>0950</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>South Africa</country>
  </location_countries>
  <link>
    <url>http://madidrop.com/</url>
    <description>Commercial website describing the main experimental device in this trial</description>
  </link>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>January 3, 2017</study_first_submitted>
  <study_first_submitted_qc>January 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 6, 2017</study_first_posted>
  <last_update_submitted>May 8, 2018</last_update_submitted>
  <last_update_submitted_qc>May 8, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 14, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Virginia</investigator_affiliation>
    <investigator_full_name>Rebecca Dillingham, MD</investigator_full_name>
    <investigator_title>Harrison Distinguished Teaching Associate Professor of Medicine and Public Health Sciences, Division of Infectious Diseases and International Health</investigator_title>
  </responsible_party>
  <keyword>water treatment</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dysentery</mesh_term>
    <mesh_term>Malnutrition</mesh_term>
    <mesh_term>Child Nutrition Disorders</mesh_term>
    <mesh_term>Diarrhea</mesh_term>
    <mesh_term>Diarrhea, Infantile</mesh_term>
  </condition_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/NCT03012048
org study id: IRB-HSR 18662
nct id: NCT03012048
lead sponsor: 
collaborator: 
has dmc: Yes
This project is a community-based randomized controlled trial designed to test the
      effectiveness of two point-of-use water treatment technologies to improve clean drinking
      water access, reduce enteropathogen burden, and improve child growth among children in
      Limpopo, South Africa.
Lack of access to safe water in low-resource settings likely contributes to stunted growth
      early in life, which affects more than a quarter of children under 5 years worldwide.
      Point-of-use water treatment technologies have the potential to provide effective and
      low-cost solutions to improving quality of drinking water in these settings. One such
      technology, a silver-impregnated ceramic disk, continually disinfects water in household
      water storage containers by diffusing silver into the water for daily treatment of 10 to 15
      liters for at least six months. Silver-impregnated ceramic water filters are another
      commercially available technology that additionally remove pathogens mechanically. While both
      technologies have proven to be highly effective in treating water, it is unknown whether the
      use of these technologies will translate to improvements in child health outcomes. This
      community-based intervention trial will estimate the effect of the silver-impregnated ceramic
      disk and a silver-impregnated ceramic water filter on linear growth of children in Limpopo,
      South Africa.

      Households in the Dzimauli community will be randomized to receive the ceramic disk, a water
      filter, the safe-storage water container alone, or no intervention. Children will be followed
      every three months for 2 years to assess height, weight, and pathogen burden in stool
      samples. Cognitive assessments will be completed at 2, 5, and 7 years of follow-up. The
      investigators hypothesize that children in households given the ceramic disk or the water
      filter will show improved linear growth compared to those in households without these
      interventions. The investigators expect that the ceramic disk will perform similarly to the
      water filter and result in similar improvements in linear growth when compared to children
      from control households.

      Estimates of effectiveness demonstrated in this trial will provide the necessary evidence
      base to support the scale-up of manufacturing and distribution of the ceramic disks and
      filters, which could provide a robust point-of-use water treatment solution for rural areas.
      By helping to identify effective tools to reduce the risk of stunting in children, the trial
      will contribute to targets to improve child health in low-resource settings.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Change in height-for-age z-score (ΔHAZ)
time frame: From 0-2 years of follow-up
description: Height measured quarterly among all children under age 15 in the households, z-scores calculated from WHO growth standards
measure: Change in weight-for-age z-score (ΔWAZ)
time frame: From 0-2 years of follow-up
description: Weight measured quarterly among all children under age 15 in the households, z-scores calculated from WHO growth standards
measure: Pathogen burden in stool samples
time frame: Quarterly from 0-2 years of follow-up
description: Non-diarrheal stools collected from the youngest child under 3 years of age in each household; testing for EAEC, EHEC/EPEC, ETEC, Shigella/EIEC, Giardia, Campylobacter, Cryptosporidium, Adenovirus by qPCR
measure: Prevalence of diarrhea
time frame: Quarterly from 0-2 years of follow-up
description: 7-day recall of diarrhea in the youngest child under 3 years of age in each household
measure: Cognitive function - Bayley Scales of Infant Development III (ages 2-3); Wechsler Preschool and Primary Scale of Intelligence III (ages 3-6); Raven's Combined Matrices (ages > 6)
time frame: 2, 5, and 7 years of follow-up
description: Cognitive assessments will be completed for the youngest child in each household (determined at enrollment) using age-appropriate developmental tests that have already been adapted, translated, and piloted in this population. Caregivers will be asked to bring their child to the local health clinic to be assessed by a Psychological Research Assistant.
measure: Silver levels in treated water samples
time frame: Quarterly from 0-2 years of follow-up
description: Treated water samples will be taken from a random subset of 50 households receiving the filter or ceramic disk every three months to determine the silver levels in treated water from the households. Total silver concentration will be measured by graphite furnace atomic absorption spectrometry (U.S.E.P.A. Method 7010).
arm group label: MadiDrop (ceramic tablet)
arm group type: Experimental
description: Households receive a MadiDrop (silver-impregnated ceramic tablet) in a safe-storage water container to use for all drinking water needs in the household. MadiDrops are replaced every 6 months over the 2-year intervention study period.
In July 2017, all households in the MadiDrop arm were crossed over to the ceramic water filter arm due to inconsistent silver release from the ceramic tablets.
arm group label: Silver-impregnated ceramic water filter
arm group type: Active Comparator
description: Households receive a silver-impregnated ceramic filter in a safe-storage water container to use for all drinking water needs in the household. Filters are replaced at the end of the 2-year intervention study period.
In December 2017, all silver-impregnated ceramic water filters were replaced with the same ceramic filters without silver due to continued inconsistencies with silver release.
arm group label: Safe-storage water container
arm group type: Active Comparator
description: Households receive a safe-storage water container alone to use for all drinking water needs in the household.
arm group label: No intervention
arm group type: No Intervention
description: Households are encouraged to continue their usual water treatment practices.
intervention type: Device
intervention name: Silver-impregnated ceramic tablet
description: A silver-impregnated ceramic disk used for drinking water treatment that was developed by engineers at the University of Virginia. When the ceramic disk is placed in a household water storage container, silver diffuses through the porous ceramic into the water at a release rate that is effective for continual disinfection of waterborne pathogens while remaining below the silver drinking water standard. The disk is effective for daily treatment of 10 to 15 liters for at least six months.
This intervention was removed from the study in July 2017 (approximately at 1 year of follow-up).
arm group label: MadiDrop (ceramic tablet)
other name: MadiDrop (trade name)
intervention type: Device
intervention name: Silver-impregnated ceramic water filter
description: Silver-impregnated ceramic water filter are well-developed, tested, and widely-used devices. In addition to mechanically removing pathogens, the filter is treated with silver to reduce live pathogens that pass through the filter and to provide residual disinfectant to reduce risk of recontamination after treatment.
This intervention was replaced with ceramic filters without silver in Dec 2017 (approximately at 1.5 years of follow-up).
arm group label: Silver-impregnated ceramic water filter
intervention type: Device
intervention name: Safe-storage water container
description: The safe-storage water containers used in this study are plastic buckets with a spigot, purchased locally.
arm group label: Safe-storage water container
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Pascal O Bessong, PhD
role: Principal Investigator
affiliation: University of Venda, Limpopo, South Africa
last name: Rebecca Dillingham, MD, MPH
role: Principal Investigator
affiliation: University of Virginia
facility: 
country: South Africa
url: http://madidrop.com/
description: Commercial website describing the main experimental device in this trial
responsible party type: Principal Investigator
investigator affiliation: University of Virginia
investigator full name: Rebecca Dillingham, MD
investigator title: Harrison Distinguished Teaching Associate Professor of Medicine and Public Health Sciences, Division of Infectious Diseases and International Health
mesh term: Dysentery
mesh term: Malnutrition
mesh term: Child Nutrition Disorders
mesh term: Diarrhea
mesh term: Diarrhea, Infantile
sharing ipd: Undecided