<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/NCT01668940</url>
  </required_header>
  <id_info>
    <org_study_id>1000031589</org_study_id>
    <nct_id>NCT01668940</nct_id>
  </id_info>
  <brief_title>Freezie Remedy to Alleviate Morning Sickness</brief_title>
  <official_title>Effectiveness of a Natural Non-medicinal Freezie Remedy to Alleviate Morning Sickness</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Hospital for Sick Children</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The Hospital for Sick Children</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to assess the effectiveness of Lillipops in the&#xD;
      improvement of morning sickness symptoms. Secondary objectives are to assess if there are any&#xD;
      changes to concurrent symptoms that may intensify NVP, such as metallic taste or&#xD;
      gastrointestinal issues (e.g. heartburn, acid reflux, indigestion and gas), as well as&#xD;
      preference for freezie flavours.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Nausea and vomiting of pregnancy (NVP) is the most common medical condition of pregnancy,&#xD;
      also known as morning sickness which affects up to 80% of pregnant women. Lillipops Iced&#xD;
      Soothies are naturally flavoured freezies developed in the United Kingdom for women with&#xD;
      morning sickness. They are available in 5 different flavours: grapefruit and tangerine, lemon&#xD;
      and mint, chamomile and orange, lime and vanilla, and ginger. The flavours are derived from&#xD;
      steam distillation of the peels (grapefruit, tangerine, lemon, orange, lime), mint leaves,&#xD;
      and chamomile flowers to release and collect their essential oils. Vanilla pods and ginger&#xD;
      are macerated and their resin is used. These flavours are chosen because they may provide&#xD;
      relief of symptoms as they are either traditional remedies for NVP, such as ginger, or&#xD;
      soothing and refreshing flavours, such as chamomile, vanilla and citrus.&#xD;
&#xD;
      This study hypothesizes that using Lillipops Iced Soothies will reduce the severity of NVP&#xD;
      symptoms according to the PUQE-24 (pregnancy-unique quantification of emesis and nausea)&#xD;
      scoring system for nausea and vomiting of pregnancy. In addition, we hypothesize concurrent&#xD;
      symptoms that may intensify NVP, such as metallic taste or gastrointestinal disorders (e.g.&#xD;
      heartburn, acid reflux, indigestion and gas), will be alleviated. We hypothesize that&#xD;
      improvements to NVP and concurrent symptoms will be greater with Lillipop freezies compared&#xD;
      to another commercially available freezie.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The study PI left the institution in early 2015.&#xD;
  </why_stopped>
  <start_date type="Actual">August 2012</start_date>
  <completion_date type="Actual">July 2015</completion_date>
  <primary_completion_date type="Actual">July 2015</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>Four parallel groups: 1) Lillipops Group (4 flavours): 2) Ginger Lillipops Group; 3) Mr. Freeze Control Group; 4) Natural Course Group. The main comparison is Group 1 vs Group 3.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>A computerized randomization table will be prepared by a third party who is not otherwise involved in the study. After a participant has given consent to enrol in the study, the next participant number in sequence will be assigned and the appropriate corresponding sealed envelope will be opened by the study coordinator, determining which product (if any) the participant will receive. The boxes will be given unique codes depending on whether they contain Lillipops (4 flavours), Ginger Lillipops or Mr. Freeze freezies, and the different flavours will also be coded. Participants will be shown a list of the ingredients that are found in Lillipops and Mr. Freeze freezies to ensure that they do not have allergies or take medications that interact with any ingredient(s) that they may be asked to consume.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Improvement of Nausea and Vomiting of Pregnancy (NVP)</measure>
    <time_frame>Baseline, +1, +3, +5, +7 days</time_frame>
    <description>To assess the effectiveness of Lillipops in the improvement of NVP symptoms. The primary endpoint of interest is the severity of NVP as compared between the 4 groups, defined according to the PUQE-24 (pregnancy-unique quantification of emesis and nausea) scoring system for nausea and vomiting of pregnancy that was developed and validated by Motherisk.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Concurrent Symptoms</measure>
    <time_frame>Baseline, +1, +3, +5, +7 days</time_frame>
    <description>To assess if there are any changes to concurrent symptoms that may intensify NVP, such as metallic taste or gastrointestinal issues (e.g. heartburn, acid reflux, indigestion and gas). The secondary endpoint of interest is the effect of the 4 groups on the status of concurrent symptoms that may intensify NVP, such as metallic taste or gastroesophageal reflux disease, as well as preference for freezie flavours, according to the PUQE-24 (pregnancy-unique quantification of emesis and nausea) scoring system for nausea and vomiting of pregnancy that was developed and validated by Motherisk.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Freezie Flavour Preference</measure>
    <time_frame>Baseline, +1, +3, +5, +7 days</time_frame>
    <description>To assess preference for freezie flavours.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">54</enrollment>
  <condition>Morning Sickness</condition>
  <arm_group>
    <arm_group_label>Lillipops Iced Soothies (4 flavours)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Initially, women will be given 1 multiflavour box of Lillipop samples minus the ginger flavour (4 flavours). Each box contains 24 freezies (20 mL each), 6 of each flavor. They will be told to eat the freezies as needed to alleviate symptoms, up to a maximum of 12 per day, and to not have any other popsicles, freezies or any ginger products throughout the duration of the study (7 days). They can request an additional multiflavour box of freezies at each follow-up, as needed.&#xD;
All participants will initially receive counselling and advice by the Motherisk NVP Counsellor about symptom management. This includes advice about dietary, non-medicinal and medical treatments as per the Motherisk NVP protocol</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Lillipop Iced Soothies (Ginger flavour)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Initially, women will be given 1 Ginger flavor box of Lillipop samples. Each box contains 24 freezies (20 mL each). Each 20ml contains 80mg of dried ginger root. They will be told to eat the freezies as needed to alleviate symptoms, up to a maximum of 12 a day and to not have any other popsicles, freezies or other ginger products throughout the duration of the study (7 days). Due ginger's antiemetic property, a maximum daily dose is up to 1000mg/day of dried ginger root powder in pregnancy.They can request an additional box of freezies at each follow-up, as needed.All participants will initially receive counselling and advice by the Motherisk NVP Counsellor about symptom management. This includes advice about dietary, non-medicinal and medical treatments as per the Motherisk NVP protocol.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Mr. Freeze Freezies (4 flavours)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Initially, women will be given 1 multiflavour box of Mr. Freeze samples. Each box contains 24 freezies (20 mL each), 6 of each flavor. They will be told to eat the freezies as needed to alleviate symptoms, up to a maximum of 12 per day, and to not have any other popsicles, freezies or any ginger products throughout the duration of the study (7 days). They can request an additional multiflavour box of freezies at each follow-up, as needed.&#xD;
All participants will initially receive counselling and advice by the Motherisk NVP Counsellor about symptom management. This includes advice about dietary, non-medicinal and medical treatments as per the Motherisk NVP protocol</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Natural Course Group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Women will not receive any freezies and will be asked to not have any other popsicles, freezies or any ginger products throughout the duration of the study (7 days).&#xD;
All participants will initially receive counselling and advice by the Motherisk NVP Counsellor about symptom management. This includes advice about dietary, non-medicinal and medical treatments as per the Motherisk NVP protocol</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Lillipops Iced Soothies (4 flavours)</intervention_name>
    <description>Lillipops Iced Soothies are naturally flavoured freezies developed in the United Kingdom for women with morning sickness. They are available in 5 different flavours: grapefruit and tangerine, lemon and mint, chamomile and orange, lime and vanilla, and ginger. The flavours are derived from steam distillation of the peels (grapefruit, tangerine, lemon, orange, lime), mint leaves, and chamomile flowers to release and collect their essential oils. Vanilla pods and ginger are macerated and their resin is used. These flavours were chosen because they may provide relief of symptoms as they are either traditional remedies for NVP, such as ginger, or soothing and refreshing flavours, such as chamomile, vanilla and citrus.</description>
    <arm_group_label>Lillipops Iced Soothies (4 flavours)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Mr. Freeze Freezies</intervention_name>
    <description>There are other commercially available freezies, such as Mr. Freeze. Mr. Freeze freezies contain simulated flavours of watermelon, cherry, blue raspberry and cream soda. However, there have been no reports, studies or claims that they are effective as a remedy for the treatment of NVP.</description>
    <arm_group_label>Mr. Freeze Freezies (4 flavours)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Lillipop Iced Soothies (Ginger flavour)</intervention_name>
    <description>Lillipops Iced Soothies are naturally flavoured freezies developed in the United Kingdom for women with morning sickness. They are available in 5 different flavours: grapefruit and tangerine, lemon and mint, chamomile and orange, lime and vanilla, and ginger.The flavours are derived from steam distillation of the peels (grapefruit, tangerine, lemon, orange, lime), mint leaves, and chamomile flowers to release and collect their essential oils. Vanilla pods and ginger are macerated and their resin is used. These flavours were chosen because they may provide relief of symptoms as they are either traditional remedies for NVP, such as ginger, or soothing and refreshing flavours, such as chamomile, vanilla and citrus.</description>
    <arm_group_label>Lillipop Iced Soothies (Ginger flavour)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pregnancy between 4 and 12 weeks gestation.&#xD;
&#xD;
          -  Pregnant women with NVP, regardless of treatment (if any) for their NVP.&#xD;
&#xD;
          -  Provide the signed informed consent form prior to initial interview.&#xD;
&#xD;
          -  Able to come in person to Sick Kids or meet at an agreed location.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Gestational age beyond 12 weeks of pregnancy.&#xD;
&#xD;
          -  Pregnant women less than 18 years of age.&#xD;
&#xD;
          -  Women who are not proficient in the English language.&#xD;
&#xD;
          -  Unable to consume any of the ingredients listed in Lillipops or Mr. Freeze freezies&#xD;
             due to allergies, medication interactions or other reasons.&#xD;
&#xD;
          -  Women refusing to avoid sources of ginger products for the duration of the study.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Shinya Ito, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Hospital for Sick Children</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Hospital for Sick Children</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 1X8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>August 16, 2012</study_first_submitted>
  <study_first_submitted_qc>August 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2012</study_first_posted>
  <results_first_submitted>April 18, 2018</results_first_submitted>
  <results_first_submitted_qc>January 6, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">January 10, 2020</results_first_posted>
  <last_update_submitted>January 6, 2020</last_update_submitted>
  <last_update_submitted_qc>January 6, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 10, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Hospital for Sick Children</investigator_affiliation>
    <investigator_full_name>Shinya Ito</investigator_full_name>
    <investigator_title>Division Head, Clinical Pharmacology and Toxicology</investigator_title>
  </responsible_party>
  <keyword>Morning Sickness</keyword>
  <keyword>Lillipops Iced Soothies</keyword>
  <keyword>Pregnancy</keyword>
  <keyword>Obstetrics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Morning Sickness</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Lillipops Iced Soothies (4 Flavours)</title>
          <description>Initially, women will be given 1 multiflavour box of Lillipop samples minus the ginger flavour (4 flavours). Each box contains 24 freezies (20 mL each), 6 of each flavor. They will be told to eat the freezies as needed to alleviate symptoms, up to a maximum of 12 per day, and to not have any other popsicles, freezies or any ginger products throughout the duration of the study (7 days). They can request an additional multiflavour box of freezies at each follow-up, as needed.&#xD;
All participants will initially receive counselling and advice by the Motherisk NVP Counsellor about symptom management. This includes advice about dietary, non-medicinal and medical treatments as per the Motherisk NVP protocol.</description>
        </group>
        <group group_id="P2">
          <title>Lillipop Iced Soothies (Ginger Flavour)</title>
          <description>Initially, women will be given 1 Ginger flavor box of Lillipop samples. Each box contains 24 freezies (20 mL each). Each 20ml contains 80mg of dried ginger root. They will be told to eat the freezies as needed to alleviate symptoms, up to a maximum of 12 a day and to not have any other popsicles, freezies or other ginger products throughout the duration of the study (7 days). Due ginger's antiemetic property, a maximum daily dose is up to 1000mg/day of dried ginger root powder in pregnancy.They can request an additional box of freezies at each follow-up, as needed.All participants will initially receive counselling and advice by the Motherisk NVP Counsellor about symptom management. This includes advice about dietary, non-medicinal and medical treatments as per the Motherisk NVP protocol.</description>
        </group>
        <group group_id="P3">
          <title>Mr. Freeze Freezies (4 Flavours)</title>
          <description>Initially, women will be given 1 multiflavour box of Mr. Freeze samples. Each box contains 24 freezies (20 mL each), 6 of each flavor. They will be told to eat the freezies as needed to alleviate symptoms, up to a maximum of 12 per day, and to not have any other popsicles, freezies or any ginger products throughout the duration of the study (7 days). They can request an additional multiflavour box of freezies at each follow-up, as needed.&#xD;
All participants will initially receive counselling and advice by the Motherisk NVP Counsellor about symptom management. This includes advice about dietary, non-medicinal and medical treatments as per the Motherisk NVP protocol&#xD;
Mr. Freeze freezies contain simulated flavours of watermelon, cherry, blue raspberry and cream soda. However, there have been no reports, studies or claims that they are effective as a remedy for the treatment of NVP.</description>
        </group>
        <group group_id="P4">
          <title>Natural Course Group</title>
          <description>Women will not receive any freezies and will be asked to not have any other popsicles, freezies or any ginger products throughout the duration of the study (7 days).&#xD;
All participants will initially receive counselling and advice by the Motherisk NVP Counsellor about symptom management. This includes advice about dietary, non-medicinal and medical treatments as per the Motherisk NVP protocol</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
                <participants group_id="P2" count="14"/>
                <participants group_id="P3" count="9"/>
                <participants group_id="P4" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="17">Data collection was completed, but data analysis did not occur due to study closure.</participants>
                <participants group_id="P2" count="14">Data collection was completed, but data analysis did not occur due to study closure.</participants>
                <participants group_id="P3" count="9">Data collection was completed, but data analysis did not occur due to study closure.</participants>
                <participants group_id="P4" count="14">Data collection was completed, but data analysis did not occur due to study closure.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Lillipops Iced Soothies (4 Flavours) (Experimental)</title>
          <description>Initially, women will be given 1 multiflavour box of Lillipop samples minus the ginger flavour (4 flavours). Each box contains 24 freezies (20 mL each), 6 of each flavor. They will be told to eat the freezies as needed to alleviate symptoms, up to a maximum of 12 per day, and to not have any other popsicles, freezies or any ginger products throughout the duration of the study (7 days). They can request an additional multiflavour box of freezies at each follow-up, as needed.&#xD;
All participants will initially receive counselling and advice by the Motherisk NVP Counsellor about symptom management. This includes advice about dietary, non-medicinal and medical treatments as per the Motherisk NVP protocol</description>
        </group>
        <group group_id="B2">
          <title>Lillipop Iced Soothies (Ginger Flavour) (Experimental)</title>
          <description>Initially, women will be given 1 Ginger flavor box of Lillipop samples. Each box contains 24 freezies (20 mL each). Each 20ml contains 80mg of dried ginger root. They will be told to eat the freezies as needed to alleviate symptoms, up to a maximum of 12 a day and to not have any other popsicles, freezies or other ginger products throughout the duration of the study (7 days). Due ginger's antiemetic property, a maximum daily dose is up to 1000mg/day of dried ginger root powder in pregnancy.They can request an additional box of freezies at each follow-up, as needed.All participants will initially receive counselling and advice by the Motherisk NVP Counsellor about symptom management. This includes advice about dietary, non-medicinal and medical treatments as per the Motherisk NVP protocol.</description>
        </group>
        <group group_id="B3">
          <title>Mr. Freeze Freezies (4 Flavours) (Active Comparator)</title>
          <description>Initially, women will be given 1 multiflavour box of Mr. Freeze samples. Each box contains 24 freezies (20 mL each), 6 of each flavor. They will be told to eat the freezies as needed to alleviate symptoms, up to a maximum of 12 per day, and to not have any other popsicles, freezies or any ginger products throughout the duration of the study (7 days). They can request an additional multiflavour box of freezies at each follow-up, as needed.&#xD;
All participants will initially receive counselling and advice by the Motherisk NVP Counsellor about symptom management. This includes advice about dietary, non-medicinal and medical treatments as per the Motherisk NVP protocol</description>
        </group>
        <group group_id="B4">
          <title>Natural Course Group (No Intervention)</title>
          <description>Women will not receive any freezies and will be asked to not have any other popsicles, freezies or any ginger products throughout the duration of the study (7 days).&#xD;
All participants will initially receive counselling and advice by the Motherisk NVP Counsellor about symptom management. This includes advice about dietary, non-medicinal and medical treatments as per the Motherisk NVP protocol</description>
        </group>
        <group group_id="B5">
          <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="17"/>
            <count group_id="B2" value="14"/>
            <count group_id="B3" value="9"/>
            <count group_id="B4" value="14"/>
            <count group_id="B5" value="54"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="14"/>
                    <measurement group_id="B5" value="54"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="31" lower_limit="25" upper_limit="37.9"/>
                    <measurement group_id="B2" value="33.9" lower_limit="26.6" upper_limit="40.8"/>
                    <measurement group_id="B3" value="33.6" lower_limit="27.3" upper_limit="41.5"/>
                    <measurement group_id="B4" value="31.8" lower_limit="27.1" upper_limit="38.9"/>
                    <measurement group_id="B5" value="32.4" lower_limit="25" upper_limit="41.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <population>All participants female as per study inclusion criteria. No analysis was completed due to study termination/closure.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="14"/>
                    <measurement group_id="B5" value="54"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <population>All participants recruited in Canada as per study inclusion criteria (i.e. ability to meet at study site or nearby location). No analysis was completed due to study termination/closure.</population>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Canada</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="14"/>
                    <measurement group_id="B5" value="54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Improvement of Nausea and Vomiting of Pregnancy (NVP)</title>
        <description>To assess the effectiveness of Lillipops in the improvement of NVP symptoms. The primary endpoint of interest is the severity of NVP as compared between the 4 groups, defined according to the PUQE-24 (pregnancy-unique quantification of emesis and nausea) scoring system for nausea and vomiting of pregnancy that was developed and validated by Motherisk.</description>
        <time_frame>Baseline, +1, +3, +5, +7 days</time_frame>
        <population>The study was terminated due to the original study PI's departure, and the final analyses have not been conducted. The study file has been locked in 2015 after the official study closure.</population>
        <group_list>
          <group group_id="O1">
            <title>Lillipops Iced Soothies (4 Flavours)</title>
            <description>Initially, women will be given 1 multiflavour box of Lillipop samples minus the ginger flavour (4 flavours). Each box contains 24 freezies (20 mL each), 6 of each flavor. They will be told to eat the freezies as needed to alleviate symptoms, up to a maximum of 12 per day, and to not have any other popsicles, freezies or any ginger products throughout the duration of the study (7 days). They can request an additional multiflavour box of freezies at each follow-up, as needed.&#xD;
All participants will initially receive counselling and advice by the Motherisk NVP Counsellor about symptom management. This includes advice about dietary, non-medicinal and medical treatments as per the Motherisk NVP protocol.</description>
          </group>
          <group group_id="O2">
            <title>Lillipop Iced Soothies (Ginger Flavour)</title>
            <description>Initially, women will be given 1 Ginger flavor box of Lillipop samples. Each box contains 24 freezies (20 mL each). Each 20ml contains 80mg of dried ginger root. They will be told to eat the freezies as needed to alleviate symptoms, up to a maximum of 12 a day and to not have any other popsicles, freezies or other ginger products throughout the duration of the study (7 days). Due ginger's antiemetic property, a maximum daily dose is up to 1000mg/day of dried ginger root powder in pregnancy.They can request an additional box of freezies at each follow-up, as needed.All participants will initially receive counselling and advice by the Motherisk NVP Counsellor about symptom management. This includes advice about dietary, non-medicinal and medical treatments as per the Motherisk NVP protocol.</description>
          </group>
          <group group_id="O3">
            <title>Mr. Freeze Freezies (4 Flavours)</title>
            <description>Initially, women will be given 1 multiflavour box of Mr. Freeze samples. Each box contains 24 freezies (20 mL each), 6 of each flavor. They will be told to eat the freezies as needed to alleviate symptoms, up to a maximum of 12 per day, and to not have any other popsicles, freezies or any ginger products throughout the duration of the study (7 days). They can request an additional multiflavour box of freezies at each follow-up, as needed.&#xD;
All participants will initially receive counselling and advice by the Motherisk NVP Counsellor about symptom management. This includes advice about dietary, non-medicinal and medical treatments as per the Motherisk NVP protocol&#xD;
Mr. Freeze freezies contain simulated flavours of watermelon, cherry, blue raspberry and cream soda. However, there have been no reports, studies or claims that they are effective as a remedy for the treatment of NVP.</description>
          </group>
          <group group_id="O4">
            <title>Natural Course Group</title>
            <description>Women will not receive any freezies and will be asked to not have any other popsicles, freezies or any ginger products throughout the duration of the study (7 days).&#xD;
All participants will initially receive counselling and advice by the Motherisk NVP Counsellor about symptom management. This includes advice about dietary, non-medicinal and medical treatments as per the Motherisk NVP protocol</description>
          </group>
        </group_list>
        <measure>
          <title>Improvement of Nausea and Vomiting of Pregnancy (NVP)</title>
          <description>To assess the effectiveness of Lillipops in the improvement of NVP symptoms. The primary endpoint of interest is the severity of NVP as compared between the 4 groups, defined according to the PUQE-24 (pregnancy-unique quantification of emesis and nausea) scoring system for nausea and vomiting of pregnancy that was developed and validated by Motherisk.</description>
          <population>The study was terminated due to the original study PI's departure, and the final analyses have not been conducted. The study file has been locked in 2015 after the official study closure.</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 group_id="O3" value="0"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Concurrent Symptoms</title>
        <description>To assess if there are any changes to concurrent symptoms that may intensify NVP, such as metallic taste or gastrointestinal issues (e.g. heartburn, acid reflux, indigestion and gas). The secondary endpoint of interest is the effect of the 4 groups on the status of concurrent symptoms that may intensify NVP, such as metallic taste or gastroesophageal reflux disease, as well as preference for freezie flavours, according to the PUQE-24 (pregnancy-unique quantification of emesis and nausea) scoring system for nausea and vomiting of pregnancy that was developed and validated by Motherisk.</description>
        <time_frame>Baseline, +1, +3, +5, +7 days</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Freezie Flavour Preference</title>
        <description>To assess preference for freezie flavours.</description>
        <time_frame>Baseline, +1, +3, +5, +7 days</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>2 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Lillipops Iced Soothies (4 Flavours)</title>
          <description>Initially, women will be given 1 multiflavour box of Lillipop samples minus the ginger flavour (4 flavours). Each box contains 24 freezies (20 mL each), 6 of each flavor. They will be told to eat the freezies as needed to alleviate symptoms, up to a maximum of 12 per day, and to not have any other popsicles, freezies or any ginger products throughout the duration of the study (7 days). They can request an additional multiflavour box of freezies at each follow-up, as needed.&#xD;
All participants will initially receive counselling and advice by the Motherisk NVP Counsellor about symptom management. This includes advice about dietary, non-medicinal and medical treatments as per the Motherisk NVP protocol.</description>
        </group>
        <group group_id="E2">
          <title>Lillipop Iced Soothies (Ginger Flavour)</title>
          <description>Initially, women will be given 1 Ginger flavor box of Lillipop samples. Each box contains 24 freezies (20 mL each). Each 20ml contains 80mg of dried ginger root. They will be told to eat the freezies as needed to alleviate symptoms, up to a maximum of 12 a day and to not have any other popsicles, freezies or other ginger products throughout the duration of the study (7 days). Due ginger's antiemetic property, a maximum daily dose is up to 1000mg/day of dried ginger root powder in pregnancy.They can request an additional box of freezies at each follow-up, as needed.All participants will initially receive counselling and advice by the Motherisk NVP Counsellor about symptom management. This includes advice about dietary, non-medicinal and medical treatments as per the Motherisk NVP protocol.</description>
        </group>
        <group group_id="E3">
          <title>Mr. Freeze Freezies (4 Flavours)</title>
          <description>Initially, women will be given 1 multiflavour box of Mr. Freeze samples. Each box contains 24 freezies (20 mL each), 6 of each flavor. They will be told to eat the freezies as needed to alleviate symptoms, up to a maximum of 12 per day, and to not have any other popsicles, freezies or any ginger products throughout the duration of the study (7 days). They can request an additional multiflavour box of freezies at each follow-up, as needed.&#xD;
All participants will initially receive counselling and advice by the Motherisk NVP Counsellor about symptom management. This includes advice about dietary, non-medicinal and medical treatments as per the Motherisk NVP protocol&#xD;
Mr. Freeze freezies contain simulated flavours of watermelon, cherry, blue raspberry and cream soda. However, there have been no reports, studies or claims that they are effective as a remedy for the treatment of NVP.</description>
        </group>
        <group group_id="E4">
          <title>Natural Course Group</title>
          <description>Women will not receive any freezies and will be asked to not have any other popsicles, freezies or any ginger products throughout the duration of the study (7 days).&#xD;
All participants will initially receive counselling and advice by the Motherisk NVP Counsellor about symptom management. This includes advice about dietary, non-medicinal and medical treatments as per the Motherisk NVP protocol</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>
    <limitations_and_caveats>Study was terminated prior to completion. Data collected from participants was not analyzed.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr Shinya Ito, Principal Investigator</name_or_title>
      <organization>The Hospital for Sick Children</organization>
      <phone>4168135776 ext 205776</phone>
      <email>shinya.ito@sickkids.ca</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/NCT01668940
org study id: 1000031589
nct id: NCT01668940
lead sponsor: 
has dmc: Yes
The primary objective of this study is to assess the effectiveness of Lillipops in the
      improvement of morning sickness symptoms. Secondary objectives are to assess if there are any
      changes to concurrent symptoms that may intensify NVP, such as metallic taste or
      gastrointestinal issues (e.g. heartburn, acid reflux, indigestion and gas), as well as
      preference for freezie flavours.
Nausea and vomiting of pregnancy (NVP) is the most common medical condition of pregnancy,
      also known as morning sickness which affects up to 80% of pregnant women. Lillipops Iced
      Soothies are naturally flavoured freezies developed in the United Kingdom for women with
      morning sickness. They are available in 5 different flavours: grapefruit and tangerine, lemon
      and mint, chamomile and orange, lime and vanilla, and ginger. The flavours are derived from
      steam distillation of the peels (grapefruit, tangerine, lemon, orange, lime), mint leaves,
      and chamomile flowers to release and collect their essential oils. Vanilla pods and ginger
      are macerated and their resin is used. These flavours are chosen because they may provide
      relief of symptoms as they are either traditional remedies for NVP, such as ginger, or
      soothing and refreshing flavours, such as chamomile, vanilla and citrus.

      This study hypothesizes that using Lillipops Iced Soothies will reduce the severity of NVP
      symptoms according to the PUQE-24 (pregnancy-unique quantification of emesis and nausea)
      scoring system for nausea and vomiting of pregnancy. In addition, we hypothesize concurrent
      symptoms that may intensify NVP, such as metallic taste or gastrointestinal disorders (e.g.
      heartburn, acid reflux, indigestion and gas), will be alleviated. We hypothesize that
      improvements to NVP and concurrent symptoms will be greater with Lillipop freezies compared
      to another commercially available freezie.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Four parallel groups: 1) Lillipops Group (4 flavours): 2) Ginger Lillipops Group; 3) Mr. Freeze Control Group; 4) Natural Course Group. The main comparison is Group 1 vs Group 3.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: A computerized randomization table will be prepared by a third party who is not otherwise involved in the study. After a participant has given consent to enrol in the study, the next participant number in sequence will be assigned and the appropriate corresponding sealed envelope will be opened by the study coordinator, determining which product (if any) the participant will receive. The boxes will be given unique codes depending on whether they contain Lillipops (4 flavours), Ginger Lillipops or Mr. Freeze freezies, and the different flavours will also be coded. Participants will be shown a list of the ingredients that are found in Lillipops and Mr. Freeze freezies to ensure that they do not have allergies or take medications that interact with any ingredient(s) that they may be asked to consume.
measure: Improvement of Nausea and Vomiting of Pregnancy (NVP)
time frame: Baseline, +1, +3, +5, +7 days
description: To assess the effectiveness of Lillipops in the improvement of NVP symptoms. The primary endpoint of interest is the severity of NVP as compared between the 4 groups, defined according to the PUQE-24 (pregnancy-unique quantification of emesis and nausea) scoring system for nausea and vomiting of pregnancy that was developed and validated by Motherisk.
measure: Concurrent Symptoms
time frame: Baseline, +1, +3, +5, +7 days
description: To assess if there are any changes to concurrent symptoms that may intensify NVP, such as metallic taste or gastrointestinal issues (e.g. heartburn, acid reflux, indigestion and gas). The secondary endpoint of interest is the effect of the 4 groups on the status of concurrent symptoms that may intensify NVP, such as metallic taste or gastroesophageal reflux disease, as well as preference for freezie flavours, according to the PUQE-24 (pregnancy-unique quantification of emesis and nausea) scoring system for nausea and vomiting of pregnancy that was developed and validated by Motherisk.
measure: Freezie Flavour Preference
time frame: Baseline, +1, +3, +5, +7 days
description: To assess preference for freezie flavours.
arm group label: Lillipops Iced Soothies (4 flavours)
arm group type: Experimental
description: Initially, women will be given 1 multiflavour box of Lillipop samples minus the ginger flavour (4 flavours). Each box contains 24 freezies (20 mL each), 6 of each flavor. They will be told to eat the freezies as needed to alleviate symptoms, up to a maximum of 12 per day, and to not have any other popsicles, freezies or any ginger products throughout the duration of the study (7 days). They can request an additional multiflavour box of freezies at each follow-up, as needed.
All participants will initially receive counselling and advice by the Motherisk NVP Counsellor about symptom management. This includes advice about dietary, non-medicinal and medical treatments as per the Motherisk NVP protocol
arm group label: Lillipop Iced Soothies (Ginger flavour)
arm group type: Experimental
description: Initially, women will be given 1 Ginger flavor box of Lillipop samples. Each box contains 24 freezies (20 mL each). Each 20ml contains 80mg of dried ginger root. They will be told to eat the freezies as needed to alleviate symptoms, up to a maximum of 12 a day and to not have any other popsicles, freezies or other ginger products throughout the duration of the study (7 days). Due ginger's antiemetic property, a maximum daily dose is up to 1000mg/day of dried ginger root powder in pregnancy.They can request an additional box of freezies at each follow-up, as needed.All participants will initially receive counselling and advice by the Motherisk NVP Counsellor about symptom management. This includes advice about dietary, non-medicinal and medical treatments as per the Motherisk NVP protocol.
arm group label: Mr. Freeze Freezies (4 flavours)
arm group type: Active Comparator
description: Initially, women will be given 1 multiflavour box of Mr. Freeze samples. Each box contains 24 freezies (20 mL each), 6 of each flavor. They will be told to eat the freezies as needed to alleviate symptoms, up to a maximum of 12 per day, and to not have any other popsicles, freezies or any ginger products throughout the duration of the study (7 days). They can request an additional multiflavour box of freezies at each follow-up, as needed.
All participants will initially receive counselling and advice by the Motherisk NVP Counsellor about symptom management. This includes advice about dietary, non-medicinal and medical treatments as per the Motherisk NVP protocol
arm group label: Natural Course Group
arm group type: No Intervention
description: Women will not receive any freezies and will be asked to not have any other popsicles, freezies or any ginger products throughout the duration of the study (7 days).
All participants will initially receive counselling and advice by the Motherisk NVP Counsellor about symptom management. This includes advice about dietary, non-medicinal and medical treatments as per the Motherisk NVP protocol
intervention type: Other
intervention name: Lillipops Iced Soothies (4 flavours)
description: Lillipops Iced Soothies are naturally flavoured freezies developed in the United Kingdom for women with morning sickness. They are available in 5 different flavours: grapefruit and tangerine, lemon and mint, chamomile and orange, lime and vanilla, and ginger. The flavours are derived from steam distillation of the peels (grapefruit, tangerine, lemon, orange, lime), mint leaves, and chamomile flowers to release and collect their essential oils. Vanilla pods and ginger are macerated and their resin is used. These flavours were chosen because they may provide relief of symptoms as they are either traditional remedies for NVP, such as ginger, or soothing and refreshing flavours, such as chamomile, vanilla and citrus.
arm group label: Lillipops Iced Soothies (4 flavours)
intervention type: Other
intervention name: Mr. Freeze Freezies
description: There are other commercially available freezies, such as Mr. Freeze. Mr. Freeze freezies contain simulated flavours of watermelon, cherry, blue raspberry and cream soda. However, there have been no reports, studies or claims that they are effective as a remedy for the treatment of NVP.
arm group label: Mr. Freeze Freezies (4 flavours)
intervention type: Other
intervention name: Lillipop Iced Soothies (Ginger flavour)
description: Lillipops Iced Soothies are naturally flavoured freezies developed in the United Kingdom for women with morning sickness. They are available in 5 different flavours: grapefruit and tangerine, lemon and mint, chamomile and orange, lime and vanilla, and ginger.The flavours are derived from steam distillation of the peels (grapefruit, tangerine, lemon, orange, lime), mint leaves, and chamomile flowers to release and collect their essential oils. Vanilla pods and ginger are macerated and their resin is used. These flavours were chosen because they may provide relief of symptoms as they are either traditional remedies for NVP, such as ginger, or soothing and refreshing flavours, such as chamomile, vanilla and citrus.
arm group label: Lillipop Iced Soothies (Ginger flavour)
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Shinya Ito, MD
role: Principal Investigator
affiliation: The Hospital for Sick Children
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: The Hospital for Sick Children
investigator full name: Shinya Ito
investigator title: Division Head, Clinical Pharmacology and Toxicology
mesh term: Morning Sickness
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Study was terminated prior to completion. Data collected from participants was not analyzed.
point of contact: 