<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/NCT03230396</url>
  </required_header>
  <id_info>
    <org_study_id>STUDY00001013</org_study_id>
    <nct_id>NCT03230396</nct_id>
  </id_info>
  <brief_title>Vitamin Gum Pharmacokinetics</brief_title>
  <official_title>Oral Release and Pharmacokinetics of Vitamins From a Gum-based Delivery System</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Penn State University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Vitaball, Inc.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Penn State University</source>
  <oversight_info>
    <has_dmc>No</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>
      The present study will investigate the oral release and systemic pharmacokinetics of a panel&#xD;
      water- and fat-soluble vitamins from two commercially-produced chewing gum formulations.&#xD;
      Vitaball, Inc. (Ft. Thomas, KY) markets a line of vitamin-fortified gums. These products&#xD;
      include Vitamingum Sport and Vitamingum Fresh, which are marketed to different consumer&#xD;
      populations. There is currently no available data on the release of vitamins from these&#xD;
      products in the oral cavity or the impact of chewing these products on plasma levels of the&#xD;
      component vitamins following acute administration. The investigators hypothesize that these&#xD;
      chewing gum products will increase both salivary and plasma levels of the component vitamins.&#xD;
      The present study has two major objectives:&#xD;
&#xD;
        1. To determine the extent to which a subset of water-soluble and fat-soluble vitamins in&#xD;
           two different Vitamingum products are released from the gum matrix and into the saliva&#xD;
           as healthy human subjects chew the gum.&#xD;
&#xD;
        2. To determine the extent to which chewing Vitamingum can acutely influence plasma levels&#xD;
           of a subset of water-soluble and fat-soluble vitamins in a population of healthy human&#xD;
           subjects.&#xD;
&#xD;
      The test articles are commercially-marketed products and are currently available to&#xD;
      participants outside the study (http://chewvitamingum.com). The present study is not intended&#xD;
      to develop a treatment for a particular disease, but rather to determine if the vitamin&#xD;
      components of these commercially-produced chewing gum products are bioaccessible or&#xD;
      bioavailable. Vitamin supplements administered as tablets, capsules, caplets, or gummies&#xD;
      might be regarded as the &quot;standard of care&quot;.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study Design The study will involve two phases. The first phase will be to compare the&#xD;
      release of the component vitamins in two chewing gum products into the saliva. This will&#xD;
      employ a parallel design in which half the subjects (7 - 8) chew a product marketed for&#xD;
      athletes &quot;Sport&quot; and half (7 - 8) chew one marketed for immune system support &quot;Immunity&quot;. The&#xD;
      second phase will be to compare the acute effects of chewing the two gums on plasma levels of&#xD;
      the component vitamins. A single-blinded, double cross-over design with 15 healthy human&#xD;
      subjects will be employed. Subjects be randomly assigned to &quot;Sport&quot;, &quot;Immunity&quot;, or a placebo&#xD;
      gum matched for color and flavor but without vitamins. Each phase will be separated by a&#xD;
      one-week washout period.&#xD;
&#xD;
      Study Procedures 1. Screening: There will be a phone screening prior to medical screening at&#xD;
      the University Park Clinical Research Center (CRC). This will be used to establish explain&#xD;
      the study to the prospective participant, establish eligibility and set up an appointment for&#xD;
      the medical screen.&#xD;
&#xD;
      2 Medical Screen: Prior to acceptance into the research study, participants must complete&#xD;
      consent forms, a medical history form, and have measurements taken (height, weight, blood&#xD;
      pressure). If female, a urine pregnancy test will be self-administered to ensure that the&#xD;
      subject is not pregnant. If the subject is still eligible after these tests, a small amount&#xD;
      of blood (10 mL) will be collected by a CRC nurse using a single needle stick. The blood will&#xD;
      be screened for markers of liver function (alanine aminotransferase, aspartate&#xD;
      aminotransferase, or bilirubin), kidney function (blood urea nitrogen), and iron status. If a&#xD;
      blood sample cannot be collected, the nurse try a second time, or to withdraw from the study.&#xD;
      If a second try is unsuccessful, the participant will be excluded from the study.&#xD;
&#xD;
      3 Research Study Overview: If eligible, the subjects will have four study days (1 visit to&#xD;
      the Food Science Building and 3 visits to the CRC). The visit to the Food Science Building&#xD;
      will be for collection of saliva samples and will last less than 1 h. The three visits to the&#xD;
      CRC will be to collect blood samples and will be scheduled from 7:30 am to 6:00 pm. During&#xD;
      this day, the subject will be required to remain at the GCRC from 7:30 am to 12:30 pm. The&#xD;
      subject will be able to leave after 6:00 pm, but will need to return at 7:30 pm for an&#xD;
      additional blood draw.&#xD;
&#xD;
      4 Prior to Study Visits: Subjects will be required to refrain from the use of any vitamin&#xD;
      supplement for one week prior to initiation of the study and for the duration of the study.&#xD;
      They may consume their normal diet during the study. On the days of the &quot;Blood Collection&quot;&#xD;
      visits, the subjects arrive at the CRC having not eaten breakfast. Breakfast will be provided&#xD;
      by the investigators prior to the insertion of the catheter. The subjects should drink plenty&#xD;
      of water on the day before and the day of the study visit.&#xD;
&#xD;
      5 Saliva Collection Visit:&#xD;
&#xD;
      a. Subjects will report to the Food Science Building at a mutually-agreed upon time.&#xD;
&#xD;
      b. Subject will be instructed to brush their teeth with a new toothbrush and toothpaste&#xD;
      (provided by investigator) prior to the start of the session.&#xD;
&#xD;
      c. Subjects will be instructed to consume 250 mL of tap water prior to starting the chewing&#xD;
      gum treatment.&#xD;
&#xD;
      d. Prior to chewing, an unstimulated baseline saliva sample will be collected. e. Subjects&#xD;
      will be randomly assigned to a treatment group and given the test gum (2 pieces of gum) and&#xD;
      instructed to chew the gum for 30 min. To standardize chewing rate, subjects will be asked to&#xD;
      chew in time to a metronome (set to 72 beats per minute) f. Subjects will then expectorate&#xD;
      into a centrifuge tube at 2, 5, 15, and 30 min after chewing is commenced.&#xD;
&#xD;
      g. All saliva produced during the 30 min experiment will be collected, as well the gum.&#xD;
&#xD;
      6 Blood Collection Visits:&#xD;
&#xD;
        1. The subjects will be asked to report to the CRC by 7:30 am. On each study day, the&#xD;
           subjects will be provided with low vitamin breakfast and lunch by the investigator. The&#xD;
           subjects will be asked to complete the meal by 8:00 am.&#xD;
&#xD;
        2. The subjects will have the option of having a numbing lotion (LMX cream containing&#xD;
           lidocaine) applied to their arm. This anesthetic takes 30 minutes to take effect. If the&#xD;
           subjects wish to use the lotion, they must tell the CRC study staff before the visit&#xD;
           since it affects the experimental timing.&#xD;
&#xD;
        3. A nurse will insert an IV catheter into a vein on their arm or hand. This will allow the&#xD;
           nurse to draw multiple blood samples without having to insert a needle each time. If the&#xD;
           first attempt to insert the catether is unsuccessful, the nurse will make a second&#xD;
           attempt. If a catether cannot be established, the participant will be excluded from the&#xD;
           rest of the study. The catheter will be removed at 4:00 pm on the first day of each set&#xD;
           of study visits. Because of the design of the research study, one additional blood&#xD;
           sample will be collected using a separate needle insertion at 8:00 pm of the visit. This&#xD;
           means that the subject will receive 2 needle insertions per visit.&#xD;
&#xD;
        4. Once the IV catheter is inserted, 10 mL of blood will be collected (~2 teaspoons).&#xD;
&#xD;
        5. The subject will then be asked to chew one (&quot;immunity&quot;) or two (&quot;sport&quot;) pieces of test&#xD;
           gum (or 2 pieces of placebo) in time with a metronome (72 beats per min) for 30 min.&#xD;
&#xD;
        6. At 15 minutes, 30 minutes and 1.5, 4.25, and 10 hours, the nurse will collect additional&#xD;
           10 mL blood samples.&#xD;
&#xD;
        7. The subject will chew one ('immunity&quot;) or 2 (&quot;sport&quot;) additional pieces of test gum (or&#xD;
           2 pieces of placebo) at 45 min, 4, and 8 hours after the insertion of the catheter (time&#xD;
           0).&#xD;
&#xD;
        8. Around noon, the subject will be given a low vitamin lunch by the CRC.&#xD;
&#xD;
        9. Because the time between blood samples increases over the course of the day, the subject&#xD;
           will be allowed to leave the CRC following collection of the 4.25 hour 10 mL blood&#xD;
           sample (12:30 pm). The nurse will remove the catheter at 12:30 pm. The subject will need&#xD;
           to come back to the CRC at 6:00 pm for a 10 hour 10 mL blood collection.&#xD;
&#xD;
       10. The second and third blood draw visits will be identical to the first visit, except the&#xD;
           subjects will be assigned to the other treatment groups.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 13, 2014</start_date>
  <completion_date type="Actual">July 1, 2015</completion_date>
  <primary_completion_date type="Actual">July 1, 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>Crossover Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Salivary vitamin levels</measure>
    <time_frame>Measured for 30 min after a single treatment with gum.</time_frame>
    <description>levels of a panel of water- and fat-soluble vitamins released from gum into the saliva.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma vitamin levels</measure>
    <time_frame>Measured over the course of 10 h in a single day after chewing placebo or experimental gums.</time_frame>
    <description>levels of a panel of water- and fat-soluble vitamins released from gum in blood plasma after chewing placebo or experimental gums.</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Nutrient Pharmacokinetics</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Commercially-available chewing gum not supplemented with vitamins. Contains: Sugar; Dextrose; Gum Base; Corn Syrup; Natural and artificial flavors; artificial colors; carnauba wax; resinous glaze; neotame; butylated hydroxytoluene.&#xD;
For saliva collection phase: No placebo is used. For blood collection phase: Subjects will chew two pieces at time = 0, 0.75, 4, and 8 h for 30 min at each time point.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vitamingum Sport</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Same gum base as placebo but supplemented with vitamins (per piece): retinyl palmitate (1250 IU); ascorbic acid (15 mg); cholecalciferol (100 IU); dl-tocopherol acetate (7.5 IU); thiamine mononitrate (375 microg); riboflavin (425 microg); niacinamide (5 mg); calcium d-panothenate (2.5 mg); pyroxidine HCl (500 microg); cyanocobalamin (1.5 microg); folic acid (100 microg); biotin (11.25 microg).&#xD;
For saliva collection phase: Subjects will chew 2 pieces for 30 min. For blood collection phase: Subjects will chew two pieces at time = 0, 0.75, 4, and 8 h for 30 min at each time point.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vitamingum Immunity</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Same gum base as placebo but supplemented with vitamins (per piece): retinyl palmitate (2000 IU); ascorbic acid (62.5 mg); cholecalciferol (200 IU); dl-tocopherol acetate (20 IU); niacinamide (10 mg); calcium d-panothenate (10 mg); pyroxidine HCl (1 mg); cyanocobalamin (5 microg); folic acid (200 microg); biotin (75 microg); zinc sulfate (2.5 mg); sodium selenite (17.5 microg); chromium picolinate (60 microg); and potassium iodide (40 microg).&#xD;
For saliva collection phase: Subjects will chew 1 pieces for 30 min. For blood collection phase: Subjects will chew 1 piece at time = 0, 0.75, 4, and 8 h for 30 min at each time point.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Vitamingum Sport</intervention_name>
    <description>Vitamin -supplemented chewing gum</description>
    <arm_group_label>Vitamingum Sport</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Vitamingum Immunity</intervention_name>
    <description>Vitamin -supplemented chewing gum</description>
    <arm_group_label>Vitamingum Immunity</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Control chewing gum. No vitamin content.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Men or women aged 18 - 60 yrs old in generally good health.&#xD;
&#xD;
          2. Healthy oral cavity with no pre-existing oral diseases including cancer,&#xD;
             periodontitis, or mucositis.&#xD;
&#xD;
          3. No chewing or swallowing disorders.&#xD;
&#xD;
          4. No known clotting disorders.&#xD;
&#xD;
          5. Willingness to follow the investigator instructions and requirements of the protocol.&#xD;
&#xD;
          6. Ability to give consent.&#xD;
&#xD;
          7. Proficiency with the English language (both written and verbal)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pre-existing oral diseases including oral cancer, periodontitis, or mucositis.&#xD;
&#xD;
          2. Chewing or swallowing disorder.&#xD;
&#xD;
          3. Iron deficiency or anemia. The level of deficiency needed for exclusion will be at the&#xD;
             discretion of the CRC physician associated with the study.&#xD;
&#xD;
          4. Pregnant, lactating, or planning to become pregnant during the study.&#xD;
&#xD;
          5. Phenylketonuric&#xD;
&#xD;
          6. Medical, social, or economic circumstance which is likely to prevent adherence to the&#xD;
             protocol.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <reference>
    <citation>Jacob RA, Swendseid ME, McKee RW, Fu CS, Clemens RA. Biochemical markers for assessment of niacin status in young men: urinary and blood levels of niacin metabolites. J Nutr. 1989 Apr;119(4):591-8. doi: 10.1093/jn/119.4.591.</citation>
    <PMID>2522982</PMID>
  </reference>
  <reference>
    <citation>Marszall ML, Lebiedzinska A, Czarnowski W, Makarowski R, Klos M, Szefer P. Application of the high-performance liquid chromatography method with coulometric detection for determination of vitamin B(6) in human plasma and serum. J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Oct 1;877(27):3151-8. doi: 10.1016/j.jchromb.2009.08.014. Epub 2009 Aug 20.</citation>
    <PMID>19733133</PMID>
  </reference>
  <reference>
    <citation>Zhao Y, Lee MJ, Cheung C, Ju JH, Chen YK, Liu B, Hu LQ, Yang CS. Analysis of multiple metabolites of tocopherols and tocotrienols in mice and humans. J Agric Food Chem. 2010 Apr 28;58(8):4844-52. doi: 10.1021/jf904464u.</citation>
    <PMID>20222730</PMID>
  </reference>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>July 24, 2017</study_first_submitted>
  <study_first_submitted_qc>July 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 26, 2017</study_first_posted>
  <last_update_submitted>August 5, 2017</last_update_submitted>
  <last_update_submitted_qc>August 5, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 8, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Penn State University</investigator_affiliation>
    <investigator_full_name>Joshua Lambert</investigator_full_name>
    <investigator_title>Associate Professor, Department of Food Science</investigator_title>
  </responsible_party>
  <keyword>vitamins</keyword>
  <keyword>dietary supplements</keyword>
  <keyword>chewing gum</keyword>
  <keyword>pharmacokinetics</keyword>
  <keyword>healthy human subjects</keyword>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>De-identified, aggregated saliva and blood level vitamin data, as well as de-identified individual saliva and blood vitamin levels data will be shared with other investigators upon request. We will include contact information for the study in resultant publications to allow other researchers to request the data. We will also summarize the results of the study on the PI's faculty webpage (http://foodscience.psu.edu/directory/jdl134) with contact information to request data.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>Data will be available upon completion of the study and acceptance of the first manuscript describing the results of the study. It will be available for a period of 5 years.</ipd_time_frame>
    <ipd_access_criteria>De-identified data will be made available to academic researchers and industry scientists. Requests for data will be reviewed by the study PI. Data will be supplied for research and teaching uses.</ipd_access_criteria>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03230396
org study id: STUDY00001013
nct id: NCT03230396
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The present study will investigate the oral release and systemic pharmacokinetics of a panel
      water- and fat-soluble vitamins from two commercially-produced chewing gum formulations.
      Vitaball, Inc. (Ft. Thomas, KY) markets a line of vitamin-fortified gums. These products
      include Vitamingum Sport and Vitamingum Fresh, which are marketed to different consumer
      populations. There is currently no available data on the release of vitamins from these
      products in the oral cavity or the impact of chewing these products on plasma levels of the
      component vitamins following acute administration. The investigators hypothesize that these
      chewing gum products will increase both salivary and plasma levels of the component vitamins.
      The present study has two major objectives:

        1. To determine the extent to which a subset of water-soluble and fat-soluble vitamins in
           two different Vitamingum products are released from the gum matrix and into the saliva
           as healthy human subjects chew the gum.

        2. To determine the extent to which chewing Vitamingum can acutely influence plasma levels
           of a subset of water-soluble and fat-soluble vitamins in a population of healthy human
           subjects.

      The test articles are commercially-marketed products and are currently available to
      participants outside the study (http://chewvitamingum.com). The present study is not intended
      to develop a treatment for a particular disease, but rather to determine if the vitamin
      components of these commercially-produced chewing gum products are bioaccessible or
      bioavailable. Vitamin supplements administered as tablets, capsules, caplets, or gummies
      might be regarded as the "standard of care".
Study Design The study will involve two phases. The first phase will be to compare the
      release of the component vitamins in two chewing gum products into the saliva. This will
      employ a parallel design in which half the subjects (7 - 8) chew a product marketed for
      athletes "Sport" and half (7 - 8) chew one marketed for immune system support "Immunity". The
      second phase will be to compare the acute effects of chewing the two gums on plasma levels of
      the component vitamins. A single-blinded, double cross-over design with 15 healthy human
      subjects will be employed. Subjects be randomly assigned to "Sport", "Immunity", or a placebo
      gum matched for color and flavor but without vitamins. Each phase will be separated by a
      one-week washout period.

      Study Procedures 1. Screening: There will be a phone screening prior to medical screening at
      the University Park Clinical Research Center (CRC). This will be used to establish explain
      the study to the prospective participant, establish eligibility and set up an appointment for
      the medical screen.

      2 Medical Screen: Prior to acceptance into the research study, participants must complete
      consent forms, a medical history form, and have measurements taken (height, weight, blood
      pressure). If female, a urine pregnancy test will be self-administered to ensure that the
      subject is not pregnant. If the subject is still eligible after these tests, a small amount
      of blood (10 mL) will be collected by a CRC nurse using a single needle stick. The blood will
      be screened for markers of liver function (alanine aminotransferase, aspartate
      aminotransferase, or bilirubin), kidney function (blood urea nitrogen), and iron status. If a
      blood sample cannot be collected, the nurse try a second time, or to withdraw from the study.
      If a second try is unsuccessful, the participant will be excluded from the study.

      3 Research Study Overview: If eligible, the subjects will have four study days (1 visit to
      the Food Science Building and 3 visits to the CRC). The visit to the Food Science Building
      will be for collection of saliva samples and will last less than 1 h. The three visits to the
      CRC will be to collect blood samples and will be scheduled from 7:30 am to 6:00 pm. During
      this day, the subject will be required to remain at the GCRC from 7:30 am to 12:30 pm. The
      subject will be able to leave after 6:00 pm, but will need to return at 7:30 pm for an
      additional blood draw.

      4 Prior to Study Visits: Subjects will be required to refrain from the use of any vitamin
      supplement for one week prior to initiation of the study and for the duration of the study.
      They may consume their normal diet during the study. On the days of the "Blood Collection"
      visits, the subjects arrive at the CRC having not eaten breakfast. Breakfast will be provided
      by the investigators prior to the insertion of the catheter. The subjects should drink plenty
      of water on the day before and the day of the study visit.

      5 Saliva Collection Visit:

      a. Subjects will report to the Food Science Building at a mutually-agreed upon time.

      b. Subject will be instructed to brush their teeth with a new toothbrush and toothpaste
      (provided by investigator) prior to the start of the session.

      c. Subjects will be instructed to consume 250 mL of tap water prior to starting the chewing
      gum treatment.

      d. Prior to chewing, an unstimulated baseline saliva sample will be collected. e. Subjects
      will be randomly assigned to a treatment group and given the test gum (2 pieces of gum) and
      instructed to chew the gum for 30 min. To standardize chewing rate, subjects will be asked to
      chew in time to a metronome (set to 72 beats per minute) f. Subjects will then expectorate
      into a centrifuge tube at 2, 5, 15, and 30 min after chewing is commenced.

      g. All saliva produced during the 30 min experiment will be collected, as well the gum.

      6 Blood Collection Visits:

        1. The subjects will be asked to report to the CRC by 7:30 am. On each study day, the
           subjects will be provided with low vitamin breakfast and lunch by the investigator. The
           subjects will be asked to complete the meal by 8:00 am.

        2. The subjects will have the option of having a numbing lotion (LMX cream containing
           lidocaine) applied to their arm. This anesthetic takes 30 minutes to take effect. If the
           subjects wish to use the lotion, they must tell the CRC study staff before the visit
           since it affects the experimental timing.

        3. A nurse will insert an IV catheter into a vein on their arm or hand. This will allow the
           nurse to draw multiple blood samples without having to insert a needle each time. If the
           first attempt to insert the catether is unsuccessful, the nurse will make a second
           attempt. If a catether cannot be established, the participant will be excluded from the
           rest of the study. The catheter will be removed at 4:00 pm on the first day of each set
           of study visits. Because of the design of the research study, one additional blood
           sample will be collected using a separate needle insertion at 8:00 pm of the visit. This
           means that the subject will receive 2 needle insertions per visit.

        4. Once the IV catheter is inserted, 10 mL of blood will be collected (~2 teaspoons).

        5. The subject will then be asked to chew one ("immunity") or two ("sport") pieces of test
           gum (or 2 pieces of placebo) in time with a metronome (72 beats per min) for 30 min.

        6. At 15 minutes, 30 minutes and 1.5, 4.25, and 10 hours, the nurse will collect additional
           10 mL blood samples.

        7. The subject will chew one ('immunity") or 2 ("sport") additional pieces of test gum (or
           2 pieces of placebo) at 45 min, 4, and 8 hours after the insertion of the catheter (time
           0).

        8. Around noon, the subject will be given a low vitamin lunch by the CRC.

        9. Because the time between blood samples increases over the course of the day, the subject
           will be allowed to leave the CRC following collection of the 4.25 hour 10 mL blood
           sample (12:30 pm). The nurse will remove the catheter at 12:30 pm. The subject will need
           to come back to the CRC at 6:00 pm for a 10 hour 10 mL blood collection.

       10. The second and third blood draw visits will be identical to the first visit, except the
           subjects will be assigned to the other treatment groups.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Single (Participant)
measure: Salivary vitamin levels
time frame: Measured for 30 min after a single treatment with gum.
description: levels of a panel of water- and fat-soluble vitamins released from gum into the saliva.
measure: Plasma vitamin levels
time frame: Measured over the course of 10 h in a single day after chewing placebo or experimental gums.
description: levels of a panel of water- and fat-soluble vitamins released from gum in blood plasma after chewing placebo or experimental gums.
arm group label: Placebo
arm group type: Placebo Comparator
description: Commercially-available chewing gum not supplemented with vitamins. Contains: Sugar; Dextrose; Gum Base; Corn Syrup; Natural and artificial flavors; artificial colors; carnauba wax; resinous glaze; neotame; butylated hydroxytoluene.
For saliva collection phase: No placebo is used. For blood collection phase: Subjects will chew two pieces at time = 0, 0.75, 4, and 8 h for 30 min at each time point.
arm group label: Vitamingum Sport
arm group type: Experimental
description: Same gum base as placebo but supplemented with vitamins (per piece): retinyl palmitate (1250 IU); ascorbic acid (15 mg); cholecalciferol (100 IU); dl-tocopherol acetate (7.5 IU); thiamine mononitrate (375 microg); riboflavin (425 microg); niacinamide (5 mg); calcium d-panothenate (2.5 mg); pyroxidine HCl (500 microg); cyanocobalamin (1.5 microg); folic acid (100 microg); biotin (11.25 microg).
For saliva collection phase: Subjects will chew 2 pieces for 30 min. For blood collection phase: Subjects will chew two pieces at time = 0, 0.75, 4, and 8 h for 30 min at each time point.
arm group label: Vitamingum Immunity
arm group type: Experimental
description: Same gum base as placebo but supplemented with vitamins (per piece): retinyl palmitate (2000 IU); ascorbic acid (62.5 mg); cholecalciferol (200 IU); dl-tocopherol acetate (20 IU); niacinamide (10 mg); calcium d-panothenate (10 mg); pyroxidine HCl (1 mg); cyanocobalamin (5 microg); folic acid (200 microg); biotin (75 microg); zinc sulfate (2.5 mg); sodium selenite (17.5 microg); chromium picolinate (60 microg); and potassium iodide (40 microg).
For saliva collection phase: Subjects will chew 1 pieces for 30 min. For blood collection phase: Subjects will chew 1 piece at time = 0, 0.75, 4, and 8 h for 30 min at each time point.
intervention type: Dietary Supplement
intervention name: Vitamingum Sport
description: Vitamin -supplemented chewing gum
arm group label: Vitamingum Sport
intervention type: Dietary Supplement
intervention name: Vitamingum Immunity
description: Vitamin -supplemented chewing gum
arm group label: Vitamingum Immunity
intervention type: Dietary Supplement
intervention name: Placebo
description: Control chewing gum. No vitamin content.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
citation: Jacob RA, Swendseid ME, McKee RW, Fu CS, Clemens RA. Biochemical markers for assessment of niacin status in young men: urinary and blood levels of niacin metabolites. J Nutr. 1989 Apr;119(4):591-8. doi: 10.1093/jn/119.4.591.
PMID: 2522982
citation: Marszall ML, Lebiedzinska A, Czarnowski W, Makarowski R, Klos M, Szefer P. Application of the high-performance liquid chromatography method with coulometric detection for determination of vitamin B(6) in human plasma and serum. J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Oct 1;877(27):3151-8. doi: 10.1016/j.jchromb.2009.08.014. Epub 2009 Aug 20.
PMID: 19733133
citation: Zhao Y, Lee MJ, Cheung C, Ju JH, Chen YK, Liu B, Hu LQ, Yang CS. Analysis of multiple metabolites of tocopherols and tocotrienols in mice and humans. J Agric Food Chem. 2010 Apr 28;58(8):4844-52. doi: 10.1021/jf904464u.
PMID: 20222730
responsible party type: Principal Investigator
investigator affiliation: Penn State University
investigator full name: Joshua Lambert
investigator title: Associate Professor, Department of Food Science
sharing ipd: Yes
ipd description: De-identified, aggregated saliva and blood level vitamin data, as well as de-identified individual saliva and blood vitamin levels data will be shared with other investigators upon request. We will include contact information for the study in resultant publications to allow other researchers to request the data. We will also summarize the results of the study on the PI's faculty webpage (http://foodscience.psu.edu/directory/jdl134) with contact information to request data.
ipd info type: Study Protocol
ipd info type: Informed Consent Form (ICF)
ipd time frame: Data will be available upon completion of the study and acceptance of the first manuscript describing the results of the study. It will be available for a period of 5 years.
ipd access criteria: De-identified data will be made available to academic researchers and industry scientists. Requests for data will be reviewed by the study PI. Data will be supplied for research and teaching uses.