<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/NCT01721395</url>
  </required_header>
  <id_info>
    <org_study_id>ZB001</org_study_id>
    <nct_id>NCT01721395</nct_id>
  </id_info>
  <brief_title>Effect of Agave Syrup, Placebo, and No Treatment on Nocturnal Cough and Sleep Quality for Coughing Infants/Toddlers and Their Parents</brief_title>
  <official_title>Effect of Agave Syrup, Placebo, and No Treatment on Nocturnal Cough and Sleep Quality for Coughing Infants/Toddlers and Their Parents</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Penn State University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Zarbee's Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Penn State University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Cough is a frequent symptom in children and infants and is one of the most common reasons&#xD;
      parents visit a healthcare provider for their child. The US Food and Drug Administration has&#xD;
      issued a warning that over-the-counter cough and cold medicines including antihistamines,&#xD;
      decongestants, anti-tussives, and expectorants should not be administered to children younger&#xD;
      than 2 years of age due not only to lack of proven efficacy, but also because of important&#xD;
      safety concerns. Honey, another method of soothing cough cannot be used in children &lt;1 year&#xD;
      due to concerns for infantile botulism. A preparation from agave syrup has been created to&#xD;
      address the need for an infant cough syrup. Although no studies have formally evaluated the&#xD;
      use of agave nectar for nocturnal cough associated with Upper Respiratory Infections, the&#xD;
      demulcent effect and sweet taste of agave nectar may provide some relief from cough in&#xD;
      children.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 2013</start_date>
  <completion_date type="Actual">March 2014</completion_date>
  <primary_completion_date type="Actual">March 2014</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>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Efficacy:Change in Cough Frequency based on parent responses to the Pediatric Cough Questionnaire</measure>
    <time_frame>Baseline (night 1) and End of night 2</time_frame>
    <description>Change from baseline in cough frequency between the first night and the end of the second night. Parents/caregivers will complete a Pediatric Cough Questionnaire (a subjective parent report of cough) using a 0-6 point Likert scale with 0=not at all to 6=extremely often to assess frequency of cough. The same parent/caregiver that completed the questionnaire in the clinic will be asked to complete the questionnaire during the follow-up telephone call.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Efficacy: Change in Response to Other symptom responses on the Pediatric Cough Questionnaire(parental report)</measure>
    <time_frame>Change from Baseline (night 1) to End of Second Night</time_frame>
    <description>Change from baseline (night 1) and the end of the second night for each of the remaining questionnaire items pertaining to cough and cold symptoms and the symptoms affect on sleep.&#xD;
Parents/caregivers will complete a Pediatric Cough Questionnaire (a subjective parent report of cold symptoms) using a 0-6 point Likert scale with 0=not at all to 6=extremely often to assess cold symptoms.&#xD;
severity of cough&#xD;
bothersome nature of cough&#xD;
how much the cough affected the child's and parent's/caregiver's ability to sleep&#xD;
severity of stuffy nose&#xD;
severity of runny nose The same parent/caregiver that completed the questionnaire in the clinic will be asked to complete the questionnaire during the follow-up telephone call.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">120</enrollment>
  <condition>Cough</condition>
  <arm_group>
    <arm_group_label>Colored, Flavored water</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The placebo will be colored to approximate the reddish amber color of the agave syrup. The placebo will use the same flavoring used in the agave syrup. The placebo will be created in a GMP facility</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Agave Syrup</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The formulation of pasteurized agave syrup consists of pasteurized agave syrup and natural flavoring.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Air-filled oral syringe</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Air-filled oral syringe to match experimental and placebo arm</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Agave Syrup</intervention_name>
    <arm_group_label>Agave Syrup</arm_group_label>
    <arm_group_label>Air-filled oral syringe</arm_group_label>
    <arm_group_label>Colored, Flavored water</arm_group_label>
    <other_name>Zarbee's Naturals Agave Baby Cough Syrup</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Otherwise healthy male or female infant who is 2 to &lt;48 months of age.&#xD;
&#xD;
          -  presents with a non-specific acute cough for 7 or fewer days' duration.&#xD;
&#xD;
          -  Parents/legal authorized representative reporting at least moderate cough and cold&#xD;
             symptoms.&#xD;
&#xD;
          -  Parent/legal authorized representative was in the home with the child on the night&#xD;
             prior to enrollment and plans to be in the home with the child on the night when study&#xD;
             treatment will be administered&#xD;
&#xD;
          -  Parent/legal authorized representative who is willing and able to comply with study&#xD;
             requirements.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous participation in this clinical trial&#xD;
&#xD;
          -  Gestational age at birth &lt;35 weeks.&#xD;
&#xD;
          -  Signs or symptoms of a more treatable disease (eg, asthma, pneumonia,&#xD;
             laryngotracheobronchitis, sinusitis, allergic rhinitis).&#xD;
&#xD;
          -  Diagnosis of influenza, bronchiolitis or respiratory syncytial virus (RSV).&#xD;
&#xD;
          -  History of reactive airways disease, asthma, or chronic lung disease.&#xD;
&#xD;
          -  Use of any medication or honey to treat cough within 6 hours of bedtime on the evening&#xD;
             prior to or on the day of enrollment.&#xD;
&#xD;
          -  Presence of any significant disease including immunodeficiency, hepatic,&#xD;
             renal,cardiovascular, or hematologic disease or any other health condition that, in&#xD;
             the opinion of the investigator, would preclude participation in the study.&#xD;
&#xD;
          -  Known allergy to agave nectar or grape flavoring&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Months</minimum_age>
    <maximum_age>48 Months</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ian M Paul, MD, MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Penn State University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Penn State Hershey Medical Center</name>
      <address>
        <city>Hershey</city>
        <state>Pennsylvania</state>
        <zip>17033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2015</verification_date>
  <study_first_submitted>October 26, 2012</study_first_submitted>
  <study_first_submitted_qc>November 1, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 4, 2012</study_first_posted>
  <last_update_submitted>October 22, 2015</last_update_submitted>
  <last_update_submitted_qc>October 22, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 23, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Penn State University</investigator_affiliation>
    <investigator_full_name>Ian M. Paul, M.D., M.Sc.</investigator_full_name>
    <investigator_title>Professor of Pediatrics and Public Health Sciences</investigator_title>
  </responsible_party>
  <keyword>Cough</keyword>
  <keyword>Nocturnal Cough</keyword>
  <keyword>Agave</keyword>
  <keyword>Sleep Quality</keyword>
  <keyword>Childhood cough</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cough</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01721395
org study id: ZB001
nct id: NCT01721395
lead sponsor: 
collaborator: 
has dmc: Yes
Cough is a frequent symptom in children and infants and is one of the most common reasons
      parents visit a healthcare provider for their child. The US Food and Drug Administration has
      issued a warning that over-the-counter cough and cold medicines including antihistamines,
      decongestants, anti-tussives, and expectorants should not be administered to children younger
      than 2 years of age due not only to lack of proven efficacy, but also because of important
      safety concerns. Honey, another method of soothing cough cannot be used in children <1 year
      due to concerns for infantile botulism. A preparation from agave syrup has been created to
      address the need for an infant cough syrup. Although no studies have formally evaluated the
      use of agave nectar for nocturnal cough associated with Upper Respiratory Infections, the
      demulcent effect and sweet taste of agave nectar may provide some relief from cough in
      children.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Efficacy:Change in Cough Frequency based on parent responses to the Pediatric Cough Questionnaire
time frame: Baseline (night 1) and End of night 2
description: Change from baseline in cough frequency between the first night and the end of the second night. Parents/caregivers will complete a Pediatric Cough Questionnaire (a subjective parent report of cough) using a 0-6 point Likert scale with 0=not at all to 6=extremely often to assess frequency of cough. The same parent/caregiver that completed the questionnaire in the clinic will be asked to complete the questionnaire during the follow-up telephone call.
measure: Efficacy: Change in Response to Other symptom responses on the Pediatric Cough Questionnaire(parental report)
time frame: Change from Baseline (night 1) to End of Second Night
description: Change from baseline (night 1) and the end of the second night for each of the remaining questionnaire items pertaining to cough and cold symptoms and the symptoms affect on sleep.
Parents/caregivers will complete a Pediatric Cough Questionnaire (a subjective parent report of cold symptoms) using a 0-6 point Likert scale with 0=not at all to 6=extremely often to assess cold symptoms.
severity of cough
bothersome nature of cough
how much the cough affected the child's and parent's/caregiver's ability to sleep
severity of stuffy nose
severity of runny nose The same parent/caregiver that completed the questionnaire in the clinic will be asked to complete the questionnaire during the follow-up telephone call.
arm group label: Colored, Flavored water
arm group type: Placebo Comparator
description: The placebo will be colored to approximate the reddish amber color of the agave syrup. The placebo will use the same flavoring used in the agave syrup. The placebo will be created in a GMP facility
arm group label: Agave Syrup
arm group type: Experimental
description: The formulation of pasteurized agave syrup consists of pasteurized agave syrup and natural flavoring.
arm group label: Air-filled oral syringe
arm group type: Sham Comparator
description: Air-filled oral syringe to match experimental and placebo arm
intervention type: Dietary Supplement
intervention name: Agave Syrup
arm group label: Agave Syrup
arm group label: Air-filled oral syringe
arm group label: Colored, Flavored water
other name: Zarbee's Naturals Agave Baby Cough Syrup
criteria: 
gender: All
minimum age: 2 Months
maximum age: 48 Months
healthy volunteers: No
last name: Ian M Paul, MD, MSc
role: Principal Investigator
affiliation: Penn State University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Penn State University
investigator full name: Ian M. Paul, M.D., M.Sc.
investigator title: Professor of Pediatrics and Public Health Sciences
mesh term: Cough