<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/NCT03782272</url>
  </required_header>
  <id_info>
    <org_study_id>1191395-1</org_study_id>
    <nct_id>NCT03782272</nct_id>
  </id_info>
  <brief_title>Safety, Acceptability, and Feasibility of Enterade®</brief_title>
  <acronym>SAFE</acronym>
  <official_title>Safety, Acceptability, and Feasibility of Enterade® in Children at Risk for Environmental Enteric Dysfunction in Kakamega County, Kenya</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>PATH</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Maseno University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Kakamega County General Teaching &amp; Referral Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>PATH</source>
  <oversight_info>
    <has_dmc>Yes</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 randomized, double-blinded, placebo-controlled pilot study to determine the safety,&#xD;
      acceptability, and feasible pediatric dosage/tolerability of enterade® solution, an amino&#xD;
      acid-based oral rehydration solution (AA-ORS), for potential use in the management of&#xD;
      environmental enteric dysfunction (EED) among children aged 12-24 months in Kakamega County,&#xD;
      Kenya.&#xD;
&#xD;
      Primary objectives:&#xD;
&#xD;
        1. To determine the safety of a 2-week course of AA-ORS among children with length-for-age&#xD;
           Z-scores (LAZ) between -1 and -3.&#xD;
&#xD;
        2. To determine the feasibility and best tolerated dose of AA-ORS among children with LAZ&#xD;
           between -3 and -1.&#xD;
&#xD;
           Secondary objectives:&#xD;
&#xD;
        3. To determine the perceptions among caregivers on the acceptability of AA-ORS as a&#xD;
           potential intervention for EED. (Qualitative)&#xD;
&#xD;
           Exploratory objectives:&#xD;
&#xD;
        4. To determine the impact of AA-ORS on markers of metabolism, gut dysfunction, systemic&#xD;
           inflammation, and micronutrient status among children with LAZ between -3 and - 1.&#xD;
&#xD;
      Qualitative results will not be reported on ClinicalTrials.gov.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Environmental enteric dysfunction (EED) is an intestinal disorder common among people living&#xD;
      in low-resource settings (LRS), which in children has been associated with increased risk of&#xD;
      growth stunting, reduced cognitive development, and reduced oral vaccine responsiveness. An&#xD;
      effective EED therapeutic would offer an opportunity to improve child growth and development&#xD;
      in LRS. One promising intervention, enterade® (an amino acid-based oral rehydration solution&#xD;
      [AA-ORS]), is a medical food product already sold in the United States. It consists of oral&#xD;
      rehydration salts and a proprietary blend of amino acids designed to restore gut function,&#xD;
      improve nutrient and electrolyte absorption, and improve barrier integrity. There is evidence&#xD;
      that this AA-ORS reduces inflammation and promotes healing of damaged intestinal epithelium&#xD;
      in murine models of intestinal damage (irradiated gut), and it may provide benefit to&#xD;
      pediatric EED patients. Supplementation of amino acids may lessen or improve intestinal&#xD;
      injury related to enteric illnesses commonly experienced in settings of poor hygiene and&#xD;
      sanitation infrastructure. The results from this exploratory mixed-methods study could have&#xD;
      broad implications for possible future studies among pediatric patients with intestinal&#xD;
      injury resulting from EED and future product development and program strategies for EED&#xD;
      interventions.&#xD;
&#xD;
      The study was terminated prematurely after study product was found on site that did not meet&#xD;
      product specifications. Enrollment and all study product dosing was halted; previously&#xD;
      enrolled participants were followed through planned study visits and assessments. An&#xD;
      additional 6-week safety follow-up period was added to study procedures. No study-related&#xD;
      adverse events were reported during per-protocol activities or from the additional 6-week&#xD;
      follow-up.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study product bottles were found on site that did not meet product specifications. This&#xD;
    prompted a 6-week safety review of participants (no study-related findings) and resulted in the&#xD;
    study's termination.&#xD;
  </why_stopped>
  <start_date type="Actual">February 26, 2019</start_date>
  <completion_date type="Actual">June 30, 2020</completion_date>
  <primary_completion_date type="Actual">March 20, 2019</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>
    <intervention_model_description>This is a mixed-methods pilot study to assess the safety, acceptability, and feasible dosage of AA-ORS among children with mild to moderate stunting (LAZ between -1 and -3) who are at risk for EED and to assess the acceptability of this fluid supplementation for their caregivers. During the main study, up to 66 child participants will be randomized to receive 14 days of AA-ORS or placebo solution daily, dosing of up to 237 ml over a 3-hour period. Study staff and participants will be blinded to the study product allocation. Caregivers will store and return unused study product. Data collection methods to include direct observation of product consumption, structured surveys with caregivers, average daily volume consumed, and measurement of plasma/serum markers of metabolism, gut dysfunction, systemic inflammation, and micro-nutrient status pre- and post-administration of product.</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Frequency of Adverse Events or Serious Adverse Events</measure>
    <time_frame>0-21 days</time_frame>
    <description>Frequency of adverse events or serious adverse events in study product and placebo arms through 21 days of follow-up as assessed by physical/clinical examination.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Volume of Daily Consumption of Study Product</measure>
    <time_frame>0-14 days</time_frame>
    <description>Total, average, and trends in daily study product volume consumed measured as milliliters per day through the 14 days of dosing.</description>
  </primary_outcome>
  <other_outcome>
    <measure>Exploratory - Metabolism: Plasma Concentration of Acylcarnitines</measure>
    <time_frame>Day 0 and Day 15</time_frame>
    <description>Plasma concentration of acylcarnitines assessed at baseline and day 15 of follow-up.</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory - Gut Damage: Plasma Concentration of Intestinal Fatty Acid-binding Protein [I-FABP]</measure>
    <time_frame>Day 0 and Day 15</time_frame>
    <description>Plasma concentration of intestinal fatty acid-binding protein [I-FABP] assessed at baseline and day 15 of follow-up.</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory - Microbial Translocation: Plasma Concentration of Soluble CD14 [sCD14]</measure>
    <time_frame>Day 0 and Day 15</time_frame>
    <description>Plasma concentration of soluble CD14 [sCD14] assessed at baseline and day 15 of follow-up.</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory - Gut Repair: Plasma Concentration of Glucagon-like Peptide 2 [GLP-2]</measure>
    <time_frame>Day 0 and Day 15</time_frame>
    <description>Plasma concentration of glucagon-like peptide 2 [GLP-2] assessed at baseline and day 15 of follow-up.</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory - Growth Hormone Axis: Plasma Concentration of Insulin-like Growth Factor 1 [IGF-1]</measure>
    <time_frame>Day 0 and Day 15</time_frame>
    <description>Plasma concentration of insulin-like growth factor 1 [IGF-1] assessed at baseline and day 15 of follow-up.</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory - Growth Hormone Axis: Plasma Concentration of Fibroblast Growth Factor 21 [FGF21]</measure>
    <time_frame>Day 0 and Day 15</time_frame>
    <description>Plasma concentration of fibroblast growth factor 21 [FGF21] assessed at baseline and day 15 of follow-up.</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory - Systemic Inflammation: Plasma Concentration of Alpha-1-acid Glycoprotein [AGP]</measure>
    <time_frame>Day 0 and Day 15</time_frame>
    <description>Plasma concentration of alpha-1-acid glycoprotein [AGP] assessed at baseline and day 15 of follow-up.</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory - Systemic Inflammation:Plasma Concentration of C-reactive Protein [CRP]</measure>
    <time_frame>Day 0 and Day 15</time_frame>
    <description>Plasma concentration of c-reactive protein [CRP] assessed at baseline and day 15 of follow-up.</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory - Micronutrient Status: Plasma Concentration of Ferritin</measure>
    <time_frame>Day 0 and Day 15</time_frame>
    <description>Plasma concentration of ferritin assessed at baseline and day 15 of follow-up.</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory - Micronutrient Status: Plasma Concentration of Soluble Transferrin Receptor [sTfR]</measure>
    <time_frame>Day 0 and Day 15</time_frame>
    <description>Plasma concentration of soluble transferrin receptor [sTfR] assessed at baseline and day 15 of follow-up.</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory - Micronutrient Status: Plasma Concentration of Retinol-binding Protein 4 [RBP4]</measure>
    <time_frame>Day 0 and Day 15</time_frame>
    <description>Plasma concentration of retinol-binding protein 4 [RBP4] assessed at baseline and day 15 of follow-up.</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory - Micronutrient Status: Plasma Concentration of Thyroglobulin</measure>
    <time_frame>Day 0 and Day 15</time_frame>
    <description>Plasma concentration of thyroglobulin assessed at baseline and day 15 of follow-up.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Stunting</condition>
  <condition>Environmental Enteric Dysfunction</condition>
  <arm_group>
    <arm_group_label>AA-ORS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Those receiving enterade oral re-hydration solution with amino acids</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Those receiving placebo solution without amino acids or rehydration salts</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Enterade</intervention_name>
    <description>enterade® (an amino acid-based oral rehydration solution [AA-ORS]) is a medical food product that consists of oral rehydration salts, natural flavor, steviol (sweetener), purified water, and a blend of amino acids that drive the uptake of water and electrolytes.</description>
    <arm_group_label>AA-ORS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>a placebo solution containing natural flavor, steviol (sweetener), and purified water.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Pediatric and caregiver pairs (must meet inclusion criteria for both categories):&#xD;
&#xD;
        Child:&#xD;
&#xD;
          1. Is between 12 and 24 months of age.&#xD;
&#xD;
          2. LAZ between -3 and -1 standard deviations (SD).&#xD;
&#xD;
          3. At least one week post routine immunization, healthy child visit, or vitamin A&#xD;
             supplementation visit at the study site.&#xD;
&#xD;
          4. Has a parent or legally acceptable representative willing and able to provide informed&#xD;
             consent.&#xD;
&#xD;
          5. No plans for travel outside of the community for the duration of the study.&#xD;
&#xD;
        Caregiver of child:&#xD;
&#xD;
          1. Is a parent or legally accepted representative of a child eligible for this study.&#xD;
&#xD;
          2. Is 18 years of age or older.&#xD;
&#xD;
          3. Has a working mobile phone.&#xD;
&#xD;
          4. Is willing and able to provide informed consent.&#xD;
&#xD;
          5. If illiterate-there is at least one literate adult living in the child's household.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Pediatric and caregiver pairs (must meet none of the exclusion criteria for either&#xD;
        category):&#xD;
&#xD;
        Child:&#xD;
&#xD;
          1. Has any sign of acute illness, including but not limited to fever, cough, and&#xD;
             diarrhea.&#xD;
&#xD;
          2. Is wasted (weight for length z-score &lt; -2 or mid-upper arm circumference [MUAC] &lt; 12.4&#xD;
             cm) or has pitting edema.&#xD;
&#xD;
          3. Is exclusively breastfed.&#xD;
&#xD;
          4. Is seeking medical attention at the health facility other than for routine,&#xD;
             preventative care (e.g., immunization visit, vitamin supplementation).&#xD;
&#xD;
          5. Has suffered within the prior week from illnesses that might impact nutritional status&#xD;
             (e.g., severe diarrhea or pneumonia; vomiting; persistent diarrhea; cleft lip or&#xD;
             palate; blindness; tuberculosis; jaundice; renal or cardiac disease; cerebral palsy;&#xD;
             known metabolic disorders; and chromosomal disorders, including trisomy 21).&#xD;
&#xD;
          6. Medical history of chronic health condition (i.e., HIV, hepatitis B or C, end stage&#xD;
             renal disease, severe liver disease-absence of a diagnosis is sufficient).&#xD;
&#xD;
          7. Participating in any other clinical trials.&#xD;
&#xD;
          8. Recent (prior 2 weeks) use of antibiotics or any other medical treatments (including&#xD;
             oral re-hydration solution), but not including vaccines or vitamin/mineral&#xD;
             supplementation).&#xD;
&#xD;
          9. Cannot give the necessary biological (blood) sample.&#xD;
&#xD;
        Caregiver:&#xD;
&#xD;
        Reports diarrhea in the household in the prior 7 days.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Months</minimum_age>
    <maximum_age>24 Months</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Kakamega County General Teaching and Referral Hospital</name>
      <address>
        <city>Kakamega</city>
        <country>Kenya</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Kenya</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>May 16, 2018</study_first_submitted>
  <study_first_submitted_qc>December 18, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 20, 2018</study_first_posted>
  <results_first_submitted>July 23, 2020</results_first_submitted>
  <results_first_submitted_qc>February 2, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">February 4, 2021</results_first_posted>
  <last_update_submitted>February 2, 2021</last_update_submitted>
  <last_update_submitted_qc>February 2, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 4, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Growth Disorders</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 28, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/72/NCT03782272/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>AA-ORS</title>
          <description>Those receiving enterade oral re-hydration solution with amino acids&#xD;
Enterade: enterade® (an amino acid-based oral rehydration solution [AA-ORS]) is a medical food product that consists of oral rehydration salts, natural flavor, steviol (sweetener), purified water, and a blend of amino acids that drive the uptake of water and electrolytes.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Those receiving placebo solution without amino acids or rehydration salts&#xD;
Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>AA-ORS</title>
          <description>Those receiving enterade oral re-hydration solution with amino acids&#xD;
Enterade: enterade® (an amino acid-based oral rehydration solution [AA-ORS]) is a medical food product that consists of oral rehydration salts, natural flavor, steviol (sweetener), purified water, and a blend of amino acids that drive the uptake of water and electrolytes.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Those receiving placebo solution without amino acids or rehydration salts&#xD;
Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="12"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>months</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="6"/>
                    <count group_id="B2" value="6"/>
                    <count group_id="B3" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18" lower_limit="12" upper_limit="23"/>
                    <measurement group_id="B2" value="16" lower_limit="13" upper_limit="21"/>
                    <measurement group_id="B3" value="18" lower_limit="12" upper_limit="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="6"/>
                    <count group_id="B2" value="6"/>
                    <count group_id="B3" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Kenya</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="6"/>
                    <count group_id="B2" value="6"/>
                    <count group_id="B3" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Length</title>
          <units>cm</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="6"/>
                    <count group_id="B2" value="6"/>
                    <count group_id="B3" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="78.95" lower_limit="71.7" upper_limit="84.5"/>
                    <measurement group_id="B2" value="75.3" lower_limit="71" upper_limit="79.3"/>
                    <measurement group_id="B3" value="78" lower_limit="71.0" upper_limit="84.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight</title>
          <units>kg</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="6"/>
                    <count group_id="B2" value="6"/>
                    <count group_id="B3" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10.55" lower_limit="9.77" upper_limit="11.3"/>
                    <measurement group_id="B2" value="9.03" lower_limit="8.5" upper_limit="10.5"/>
                    <measurement group_id="B3" value="10.0" lower_limit="8.5" upper_limit="11.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Mid-upper arm circumference (MUAC)</title>
          <units>mm</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="6"/>
                    <count group_id="B2" value="6"/>
                    <count group_id="B3" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="150.5" lower_limit="142" upper_limit="164"/>
                    <measurement group_id="B2" value="141" lower_limit="138" upper_limit="150"/>
                    <measurement group_id="B3" value="145" lower_limit="138" upper_limit="164"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Frequency of Adverse Events or Serious Adverse Events</title>
        <description>Frequency of adverse events or serious adverse events in study product and placebo arms through 21 days of follow-up as assessed by physical/clinical examination.</description>
        <time_frame>0-21 days</time_frame>
        <population>This is the intention-to-treat population with all participants randomized and received at least one dose.</population>
        <group_list>
          <group group_id="O1">
            <title>AA-ORS</title>
            <description>Those receiving enterade oral re-hydration solution with amino acids&#xD;
Enterade: enterade® (an amino acid-based oral rehydration solution [AA-ORS]) is a medical food product that consists of oral rehydration salts, natural flavor, steviol (sweetener), purified water, and a blend of amino acids that drive the uptake of water and electrolytes.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Those receiving placebo solution without amino acids or rehydration salts&#xD;
Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.</description>
          </group>
        </group_list>
        <measure>
          <title>Frequency of Adverse Events or Serious Adverse Events</title>
          <description>Frequency of adverse events or serious adverse events in study product and placebo arms through 21 days of follow-up as assessed by physical/clinical examination.</description>
          <population>This is the intention-to-treat population with all participants randomized and received at least one dose.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Volume of Daily Consumption of Study Product</title>
        <description>Total, average, and trends in daily study product volume consumed measured as milliliters per day through the 14 days of dosing.</description>
        <time_frame>0-14 days</time_frame>
        <population>Intention-to-treat</population>
        <group_list>
          <group group_id="O1">
            <title>Pooled Arms</title>
            <description>Due to study termination, insufficient data was collected for per-arm analysis. Only 2 participants completed the study per-protocol with a total of 12 having at least one dose of study product (target sample size was 66). Both AA-ORS and placebo arms data are pooled together.</description>
          </group>
        </group_list>
        <measure>
          <title>Volume of Daily Consumption of Study Product</title>
          <description>Total, average, and trends in daily study product volume consumed measured as milliliters per day through the 14 days of dosing.</description>
          <population>Intention-to-treat</population>
          <units>ml</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="212.5" lower_limit="181" upper_limit="234"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Exploratory - Metabolism: Plasma Concentration of Acylcarnitines</title>
        <description>Plasma concentration of acylcarnitines assessed at baseline and day 15 of follow-up.</description>
        <time_frame>Day 0 and Day 15</time_frame>
        <population>Due to study termination, exploratory analyses were not conducted on specimens collected.</population>
        <group_list>
          <group group_id="O1">
            <title>AA-ORS</title>
            <description>Those receiving enterade oral re-hydration solution with amino acids&#xD;
Enterade: enterade® (an amino acid-based oral rehydration solution [AA-ORS]) is a medical food product that consists of oral rehydration salts, natural flavor, steviol (sweetener), purified water, and a blend of amino acids that drive the uptake of water and electrolytes.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Those receiving placebo solution without amino acids or rehydration salts&#xD;
Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.</description>
          </group>
        </group_list>
        <measure>
          <title>Exploratory - Metabolism: Plasma Concentration of Acylcarnitines</title>
          <description>Plasma concentration of acylcarnitines assessed at baseline and day 15 of follow-up.</description>
          <population>Due to study termination, exploratory analyses were not conducted on specimens collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Exploratory - Gut Damage: Plasma Concentration of Intestinal Fatty Acid-binding Protein [I-FABP]</title>
        <description>Plasma concentration of intestinal fatty acid-binding protein [I-FABP] assessed at baseline and day 15 of follow-up.</description>
        <time_frame>Day 0 and Day 15</time_frame>
        <population>Due to study termination, exploratory analyses were not conducted on specimens collected.</population>
        <group_list>
          <group group_id="O1">
            <title>AA-ORS</title>
            <description>Those receiving enterade oral re-hydration solution with amino acids&#xD;
Enterade: enterade® (an amino acid-based oral rehydration solution [AA-ORS]) is a medical food product that consists of oral rehydration salts, natural flavor, steviol (sweetener), purified water, and a blend of amino acids that drive the uptake of water and electrolytes.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Those receiving placebo solution without amino acids or rehydration salts&#xD;
Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.</description>
          </group>
        </group_list>
        <measure>
          <title>Exploratory - Gut Damage: Plasma Concentration of Intestinal Fatty Acid-binding Protein [I-FABP]</title>
          <description>Plasma concentration of intestinal fatty acid-binding protein [I-FABP] assessed at baseline and day 15 of follow-up.</description>
          <population>Due to study termination, exploratory analyses were not conducted on specimens collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Exploratory - Microbial Translocation: Plasma Concentration of Soluble CD14 [sCD14]</title>
        <description>Plasma concentration of soluble CD14 [sCD14] assessed at baseline and day 15 of follow-up.</description>
        <time_frame>Day 0 and Day 15</time_frame>
        <population>Due to study termination, exploratory analyses were not conducted on specimens collected.</population>
        <group_list>
          <group group_id="O1">
            <title>AA-ORS</title>
            <description>Those receiving enterade oral re-hydration solution with amino acids&#xD;
Enterade: enterade® (an amino acid-based oral rehydration solution [AA-ORS]) is a medical food product that consists of oral rehydration salts, natural flavor, steviol (sweetener), purified water, and a blend of amino acids that drive the uptake of water and electrolytes.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Those receiving placebo solution without amino acids or rehydration salts&#xD;
Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.</description>
          </group>
        </group_list>
        <measure>
          <title>Exploratory - Microbial Translocation: Plasma Concentration of Soluble CD14 [sCD14]</title>
          <description>Plasma concentration of soluble CD14 [sCD14] assessed at baseline and day 15 of follow-up.</description>
          <population>Due to study termination, exploratory analyses were not conducted on specimens collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Exploratory - Gut Repair: Plasma Concentration of Glucagon-like Peptide 2 [GLP-2]</title>
        <description>Plasma concentration of glucagon-like peptide 2 [GLP-2] assessed at baseline and day 15 of follow-up.</description>
        <time_frame>Day 0 and Day 15</time_frame>
        <population>Due to study termination, exploratory analyses were not conducted on specimens collected.</population>
        <group_list>
          <group group_id="O1">
            <title>AA-ORS</title>
            <description>Those receiving enterade oral re-hydration solution with amino acids&#xD;
Enterade: enterade® (an amino acid-based oral rehydration solution [AA-ORS]) is a medical food product that consists of oral rehydration salts, natural flavor, steviol (sweetener), purified water, and a blend of amino acids that drive the uptake of water and electrolytes.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Those receiving placebo solution without amino acids or rehydration salts&#xD;
Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.</description>
          </group>
        </group_list>
        <measure>
          <title>Exploratory - Gut Repair: Plasma Concentration of Glucagon-like Peptide 2 [GLP-2]</title>
          <description>Plasma concentration of glucagon-like peptide 2 [GLP-2] assessed at baseline and day 15 of follow-up.</description>
          <population>Due to study termination, exploratory analyses were not conducted on specimens collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Exploratory - Growth Hormone Axis: Plasma Concentration of Insulin-like Growth Factor 1 [IGF-1]</title>
        <description>Plasma concentration of insulin-like growth factor 1 [IGF-1] assessed at baseline and day 15 of follow-up.</description>
        <time_frame>Day 0 and Day 15</time_frame>
        <population>Due to study termination, exploratory analyses were not conducted on specimens collected.</population>
        <group_list>
          <group group_id="O1">
            <title>AA-ORS</title>
            <description>Those receiving enterade oral re-hydration solution with amino acids&#xD;
Enterade: enterade® (an amino acid-based oral rehydration solution [AA-ORS]) is a medical food product that consists of oral rehydration salts, natural flavor, steviol (sweetener), purified water, and a blend of amino acids that drive the uptake of water and electrolytes.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Those receiving placebo solution without amino acids or rehydration salts&#xD;
Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.</description>
          </group>
        </group_list>
        <measure>
          <title>Exploratory - Growth Hormone Axis: Plasma Concentration of Insulin-like Growth Factor 1 [IGF-1]</title>
          <description>Plasma concentration of insulin-like growth factor 1 [IGF-1] assessed at baseline and day 15 of follow-up.</description>
          <population>Due to study termination, exploratory analyses were not conducted on specimens collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Exploratory - Growth Hormone Axis: Plasma Concentration of Fibroblast Growth Factor 21 [FGF21]</title>
        <description>Plasma concentration of fibroblast growth factor 21 [FGF21] assessed at baseline and day 15 of follow-up.</description>
        <time_frame>Day 0 and Day 15</time_frame>
        <population>Due to study termination, exploratory analyses were not conducted on specimens collected.</population>
        <group_list>
          <group group_id="O1">
            <title>AA-ORS</title>
            <description>Those receiving enterade oral re-hydration solution with amino acids&#xD;
Enterade: enterade® (an amino acid-based oral rehydration solution [AA-ORS]) is a medical food product that consists of oral rehydration salts, natural flavor, steviol (sweetener), purified water, and a blend of amino acids that drive the uptake of water and electrolytes.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Those receiving placebo solution without amino acids or rehydration salts&#xD;
Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.</description>
          </group>
        </group_list>
        <measure>
          <title>Exploratory - Growth Hormone Axis: Plasma Concentration of Fibroblast Growth Factor 21 [FGF21]</title>
          <description>Plasma concentration of fibroblast growth factor 21 [FGF21] assessed at baseline and day 15 of follow-up.</description>
          <population>Due to study termination, exploratory analyses were not conducted on specimens collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Exploratory - Systemic Inflammation: Plasma Concentration of Alpha-1-acid Glycoprotein [AGP]</title>
        <description>Plasma concentration of alpha-1-acid glycoprotein [AGP] assessed at baseline and day 15 of follow-up.</description>
        <time_frame>Day 0 and Day 15</time_frame>
        <population>Due to study termination, exploratory analyses were not conducted on specimens collected.</population>
        <group_list>
          <group group_id="O1">
            <title>AA-ORS</title>
            <description>Those receiving enterade oral re-hydration solution with amino acids&#xD;
Enterade: enterade® (an amino acid-based oral rehydration solution [AA-ORS]) is a medical food product that consists of oral rehydration salts, natural flavor, steviol (sweetener), purified water, and a blend of amino acids that drive the uptake of water and electrolytes.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Those receiving placebo solution without amino acids or rehydration salts&#xD;
Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.</description>
          </group>
        </group_list>
        <measure>
          <title>Exploratory - Systemic Inflammation: Plasma Concentration of Alpha-1-acid Glycoprotein [AGP]</title>
          <description>Plasma concentration of alpha-1-acid glycoprotein [AGP] assessed at baseline and day 15 of follow-up.</description>
          <population>Due to study termination, exploratory analyses were not conducted on specimens collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Exploratory - Systemic Inflammation:Plasma Concentration of C-reactive Protein [CRP]</title>
        <description>Plasma concentration of c-reactive protein [CRP] assessed at baseline and day 15 of follow-up.</description>
        <time_frame>Day 0 and Day 15</time_frame>
        <population>Due to study termination, exploratory analyses were not conducted on specimens collected.</population>
        <group_list>
          <group group_id="O1">
            <title>AA-ORS</title>
            <description>Those receiving enterade oral re-hydration solution with amino acids&#xD;
Enterade: enterade® (an amino acid-based oral rehydration solution [AA-ORS]) is a medical food product that consists of oral rehydration salts, natural flavor, steviol (sweetener), purified water, and a blend of amino acids that drive the uptake of water and electrolytes.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Those receiving placebo solution without amino acids or rehydration salts&#xD;
Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.</description>
          </group>
        </group_list>
        <measure>
          <title>Exploratory - Systemic Inflammation:Plasma Concentration of C-reactive Protein [CRP]</title>
          <description>Plasma concentration of c-reactive protein [CRP] assessed at baseline and day 15 of follow-up.</description>
          <population>Due to study termination, exploratory analyses were not conducted on specimens collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Exploratory - Micronutrient Status: Plasma Concentration of Ferritin</title>
        <description>Plasma concentration of ferritin assessed at baseline and day 15 of follow-up.</description>
        <time_frame>Day 0 and Day 15</time_frame>
        <population>Due to study termination, exploratory analyses were not conducted on specimens collected.</population>
        <group_list>
          <group group_id="O1">
            <title>AA-ORS</title>
            <description>Those receiving enterade oral re-hydration solution with amino acids&#xD;
Enterade: enterade® (an amino acid-based oral rehydration solution [AA-ORS]) is a medical food product that consists of oral rehydration salts, natural flavor, steviol (sweetener), purified water, and a blend of amino acids that drive the uptake of water and electrolytes.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Those receiving placebo solution without amino acids or rehydration salts&#xD;
Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.</description>
          </group>
        </group_list>
        <measure>
          <title>Exploratory - Micronutrient Status: Plasma Concentration of Ferritin</title>
          <description>Plasma concentration of ferritin assessed at baseline and day 15 of follow-up.</description>
          <population>Due to study termination, exploratory analyses were not conducted on specimens collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Exploratory - Micronutrient Status: Plasma Concentration of Soluble Transferrin Receptor [sTfR]</title>
        <description>Plasma concentration of soluble transferrin receptor [sTfR] assessed at baseline and day 15 of follow-up.</description>
        <time_frame>Day 0 and Day 15</time_frame>
        <population>Due to study termination, exploratory analyses were not conducted on specimens collected.</population>
        <group_list>
          <group group_id="O1">
            <title>AA-ORS</title>
            <description>Those receiving enterade oral re-hydration solution with amino acids&#xD;
Enterade: enterade® (an amino acid-based oral rehydration solution [AA-ORS]) is a medical food product that consists of oral rehydration salts, natural flavor, steviol (sweetener), purified water, and a blend of amino acids that drive the uptake of water and electrolytes.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Those receiving placebo solution without amino acids or rehydration salts&#xD;
Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.</description>
          </group>
        </group_list>
        <measure>
          <title>Exploratory - Micronutrient Status: Plasma Concentration of Soluble Transferrin Receptor [sTfR]</title>
          <description>Plasma concentration of soluble transferrin receptor [sTfR] assessed at baseline and day 15 of follow-up.</description>
          <population>Due to study termination, exploratory analyses were not conducted on specimens collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Exploratory - Micronutrient Status: Plasma Concentration of Retinol-binding Protein 4 [RBP4]</title>
        <description>Plasma concentration of retinol-binding protein 4 [RBP4] assessed at baseline and day 15 of follow-up.</description>
        <time_frame>Day 0 and Day 15</time_frame>
        <population>Due to study termination, exploratory analyses were not conducted on specimens collected.</population>
        <group_list>
          <group group_id="O1">
            <title>AA-ORS</title>
            <description>Those receiving enterade oral re-hydration solution with amino acids&#xD;
Enterade: enterade® (an amino acid-based oral rehydration solution [AA-ORS]) is a medical food product that consists of oral rehydration salts, natural flavor, steviol (sweetener), purified water, and a blend of amino acids that drive the uptake of water and electrolytes.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Those receiving placebo solution without amino acids or rehydration salts&#xD;
Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.</description>
          </group>
        </group_list>
        <measure>
          <title>Exploratory - Micronutrient Status: Plasma Concentration of Retinol-binding Protein 4 [RBP4]</title>
          <description>Plasma concentration of retinol-binding protein 4 [RBP4] assessed at baseline and day 15 of follow-up.</description>
          <population>Due to study termination, exploratory analyses were not conducted on specimens collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Exploratory - Micronutrient Status: Plasma Concentration of Thyroglobulin</title>
        <description>Plasma concentration of thyroglobulin assessed at baseline and day 15 of follow-up.</description>
        <time_frame>Day 0 and Day 15</time_frame>
        <population>Due to study termination, exploratory analyses were not conducted on specimens collected.</population>
        <group_list>
          <group group_id="O1">
            <title>AA-ORS</title>
            <description>Those receiving enterade oral re-hydration solution with amino acids&#xD;
Enterade: enterade® (an amino acid-based oral rehydration solution [AA-ORS]) is a medical food product that consists of oral rehydration salts, natural flavor, steviol (sweetener), purified water, and a blend of amino acids that drive the uptake of water and electrolytes.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Those receiving placebo solution without amino acids or rehydration salts&#xD;
Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.</description>
          </group>
        </group_list>
        <measure>
          <title>Exploratory - Micronutrient Status: Plasma Concentration of Thyroglobulin</title>
          <description>Plasma concentration of thyroglobulin assessed at baseline and day 15 of follow-up.</description>
          <population>Due to study termination, exploratory analyses were not conducted on specimens collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>21 days</time_frame>
      <group_list>
        <group group_id="E1">
          <title>AA-ORS</title>
          <description>Those receiving enterade oral re-hydration solution with amino acids&#xD;
Enterade: enterade® (an amino acid-based oral rehydration solution [AA-ORS]) is a medical food product that consists of oral rehydration salts, natural flavor, steviol (sweetener), purified water, and a blend of amino acids that drive the uptake of water and electrolytes.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Those receiving placebo solution without amino acids or rehydration salts&#xD;
Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Gwen Ambler, Clinical Research Officer</name_or_title>
      <organization>PATH</organization>
      <phone>+1-206-285-3500</phone>
      <email>gambler@path.org</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03782272
org study id: 1191395-1
nct id: NCT03782272
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a randomized, double-blinded, placebo-controlled pilot study to determine the safety,
      acceptability, and feasible pediatric dosage/tolerability of enterade® solution, an amino
      acid-based oral rehydration solution (AA-ORS), for potential use in the management of
      environmental enteric dysfunction (EED) among children aged 12-24 months in Kakamega County,
      Kenya.

      Primary objectives:

        1. To determine the safety of a 2-week course of AA-ORS among children with length-for-age
           Z-scores (LAZ) between -1 and -3.

        2. To determine the feasibility and best tolerated dose of AA-ORS among children with LAZ
           between -3 and -1.

           Secondary objectives:

        3. To determine the perceptions among caregivers on the acceptability of AA-ORS as a
           potential intervention for EED. (Qualitative)

           Exploratory objectives:

        4. To determine the impact of AA-ORS on markers of metabolism, gut dysfunction, systemic
           inflammation, and micronutrient status among children with LAZ between -3 and - 1.

      Qualitative results will not be reported on ClinicalTrials.gov.
Environmental enteric dysfunction (EED) is an intestinal disorder common among people living
      in low-resource settings (LRS), which in children has been associated with increased risk of
      growth stunting, reduced cognitive development, and reduced oral vaccine responsiveness. An
      effective EED therapeutic would offer an opportunity to improve child growth and development
      in LRS. One promising intervention, enterade® (an amino acid-based oral rehydration solution
      [AA-ORS]), is a medical food product already sold in the United States. It consists of oral
      rehydration salts and a proprietary blend of amino acids designed to restore gut function,
      improve nutrient and electrolyte absorption, and improve barrier integrity. There is evidence
      that this AA-ORS reduces inflammation and promotes healing of damaged intestinal epithelium
      in murine models of intestinal damage (irradiated gut), and it may provide benefit to
      pediatric EED patients. Supplementation of amino acids may lessen or improve intestinal
      injury related to enteric illnesses commonly experienced in settings of poor hygiene and
      sanitation infrastructure. The results from this exploratory mixed-methods study could have
      broad implications for possible future studies among pediatric patients with intestinal
      injury resulting from EED and future product development and program strategies for EED
      interventions.

      The study was terminated prematurely after study product was found on site that did not meet
      product specifications. Enrollment and all study product dosing was halted; previously
      enrolled participants were followed through planned study visits and assessments. An
      additional 6-week safety follow-up period was added to study procedures. No study-related
      adverse events were reported during per-protocol activities or from the additional 6-week
      follow-up.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a mixed-methods pilot study to assess the safety, acceptability, and feasible dosage of AA-ORS among children with mild to moderate stunting (LAZ between -1 and -3) who are at risk for EED and to assess the acceptability of this fluid supplementation for their caregivers. During the main study, up to 66 child participants will be randomized to receive 14 days of AA-ORS or placebo solution daily, dosing of up to 237 ml over a 3-hour period. Study staff and participants will be blinded to the study product allocation. Caregivers will store and return unused study product. Data collection methods to include direct observation of product consumption, structured surveys with caregivers, average daily volume consumed, and measurement of plasma/serum markers of metabolism, gut dysfunction, systemic inflammation, and micro-nutrient status pre- and post-administration of product.
primary purpose: Other
masking: Triple (Participant, Care Provider, Investigator)
measure: Frequency of Adverse Events or Serious Adverse Events
time frame: 0-21 days
description: Frequency of adverse events or serious adverse events in study product and placebo arms through 21 days of follow-up as assessed by physical/clinical examination.
measure: Volume of Daily Consumption of Study Product
time frame: 0-14 days
description: Total, average, and trends in daily study product volume consumed measured as milliliters per day through the 14 days of dosing.
measure: Exploratory - Metabolism: Plasma Concentration of Acylcarnitines
time frame: Day 0 and Day 15
description: Plasma concentration of acylcarnitines assessed at baseline and day 15 of follow-up.
measure: Exploratory - Gut Damage: Plasma Concentration of Intestinal Fatty Acid-binding Protein [I-FABP]
time frame: Day 0 and Day 15
description: Plasma concentration of intestinal fatty acid-binding protein [I-FABP] assessed at baseline and day 15 of follow-up.
measure: Exploratory - Microbial Translocation: Plasma Concentration of Soluble CD14 [sCD14]
time frame: Day 0 and Day 15
description: Plasma concentration of soluble CD14 [sCD14] assessed at baseline and day 15 of follow-up.
measure: Exploratory - Gut Repair: Plasma Concentration of Glucagon-like Peptide 2 [GLP-2]
time frame: Day 0 and Day 15
description: Plasma concentration of glucagon-like peptide 2 [GLP-2] assessed at baseline and day 15 of follow-up.
measure: Exploratory - Growth Hormone Axis: Plasma Concentration of Insulin-like Growth Factor 1 [IGF-1]
time frame: Day 0 and Day 15
description: Plasma concentration of insulin-like growth factor 1 [IGF-1] assessed at baseline and day 15 of follow-up.
measure: Exploratory - Growth Hormone Axis: Plasma Concentration of Fibroblast Growth Factor 21 [FGF21]
time frame: Day 0 and Day 15
description: Plasma concentration of fibroblast growth factor 21 [FGF21] assessed at baseline and day 15 of follow-up.
measure: Exploratory - Systemic Inflammation: Plasma Concentration of Alpha-1-acid Glycoprotein [AGP]
time frame: Day 0 and Day 15
description: Plasma concentration of alpha-1-acid glycoprotein [AGP] assessed at baseline and day 15 of follow-up.
measure: Exploratory - Systemic Inflammation:Plasma Concentration of C-reactive Protein [CRP]
time frame: Day 0 and Day 15
description: Plasma concentration of c-reactive protein [CRP] assessed at baseline and day 15 of follow-up.
measure: Exploratory - Micronutrient Status: Plasma Concentration of Ferritin
time frame: Day 0 and Day 15
description: Plasma concentration of ferritin assessed at baseline and day 15 of follow-up.
measure: Exploratory - Micronutrient Status: Plasma Concentration of Soluble Transferrin Receptor [sTfR]
time frame: Day 0 and Day 15
description: Plasma concentration of soluble transferrin receptor [sTfR] assessed at baseline and day 15 of follow-up.
measure: Exploratory - Micronutrient Status: Plasma Concentration of Retinol-binding Protein 4 [RBP4]
time frame: Day 0 and Day 15
description: Plasma concentration of retinol-binding protein 4 [RBP4] assessed at baseline and day 15 of follow-up.
measure: Exploratory - Micronutrient Status: Plasma Concentration of Thyroglobulin
time frame: Day 0 and Day 15
description: Plasma concentration of thyroglobulin assessed at baseline and day 15 of follow-up.
arm group label: AA-ORS
arm group type: Experimental
description: Those receiving enterade oral re-hydration solution with amino acids
arm group label: Placebo
arm group type: Placebo Comparator
description: Those receiving placebo solution without amino acids or rehydration salts
intervention type: Dietary Supplement
intervention name: Enterade
description: enterade® (an amino acid-based oral rehydration solution [AA-ORS]) is a medical food product that consists of oral rehydration salts, natural flavor, steviol (sweetener), purified water, and a blend of amino acids that drive the uptake of water and electrolytes.
arm group label: AA-ORS
intervention type: Dietary Supplement
intervention name: Placebo
description: a placebo solution containing natural flavor, steviol (sweetener), and purified water.
arm group label: Placebo
criteria: 
gender: All
minimum age: 12 Months
maximum age: 24 Months
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Kenya
responsible party type: Sponsor
mesh term: Growth Disorders
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 