<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/NCT02968992</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00094982</org_study_id>
    <nct_id>NCT02968992</nct_id>
  </id_info>
  <brief_title>Effects of rhLactoferrin on Chronic Inflammation in the Elderly</brief_title>
  <acronym>ELCIE</acronym>
  <official_title>Effects of Lactoferrin on Chronic Inflammation in the Elderly</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Johns Hopkins University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ventria Bioscience</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Johns Hopkins University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to investigate how recombinant human lactoferrin (rhLF) which is&#xD;
      a partially iron saturated form of lactoferrin produced and purified from rice grain may&#xD;
      improve mobility and memory in older adults with chronic inflammation. Lactoferrin, is a&#xD;
      known multifunctional protein, and has been shown to have anti-inflammatory effects. A&#xD;
      recombinant human version of this protein was recently developed and produced from rice. This&#xD;
      is now available from the Ventria Bioscience Company in a controlled, pharmaceutical grade&#xD;
      capsule. As part of this double blinded and randomized study, participants will take daily&#xD;
      dosages of recombinant human lactoferrin (rhLF) or its matched placebo; to measure the&#xD;
      effects of rhlactoferrin on chronic inflammation and its association with improving mobility&#xD;
      and memory over a 6 month time period. During the study all participants will be asked to&#xD;
      provide blood samples and will have physical and cognitive tests administered to them. By&#xD;
      measuring biomarkers in the blood as well as changes in physical and cognitive measures, the&#xD;
      investigators will gain an understanding of how rhlactoferrin may safely improve measures of&#xD;
      chronic inflammation in older adults. As well as a better understanding of whether it has the&#xD;
      potential to meaningfully influence important measures of physical and cognitive function&#xD;
      known to be influenced by Chronic Inflammation (CI).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary objective of this study is to examine in a double blinded and randomized trial&#xD;
      the efficacy of Recombinant Human lactoferrin (rhLF) in reducing chronic inflammation as&#xD;
      measured by IL-6 and sTNFR1 in the bloodstream. The primary end point is to gather&#xD;
      information about the tolerability of and adherence to oral rhlactoferrin (rhLF) among older&#xD;
      adults with CI over a six-month period. The exploratory objective is to assess the efficacy&#xD;
      of rhlactoferrin (rhLF) in attenuating cognitive decline as measured by the Digit Symbol&#xD;
      Substitution Test and Trail Making Test, as well as improving physical mobility as measured&#xD;
      by performance on 4 meter and six-minute walk tests. Further physical and functional&#xD;
      measurement data will be gather using an Acti-graph link Activity monitor, the raw data&#xD;
      collected will be used to : (i) characterize cumulative daily activity, (ii) assess daily&#xD;
      circadian patterns of activity, (iii) assess physical activity variability, (iv) model&#xD;
      patterns of daily activity, and (iv) estimate walking speed. This additional data will&#xD;
      complement mobility measures by describing function enacted in daily life&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 14, 2017</start_date>
  <completion_date type="Actual">February 25, 2019</completion_date>
  <primary_completion_date type="Actual">February 25, 2019</primary_completion_date>
  <phase>Phase 2</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>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>•Randomized: Participants are assigned to intervention groups by chance</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>The Effect of Rhlactoferrin on Serum Levels of Interleukin-6 (IL-6)</measure>
    <time_frame>Baseline and 6 months</time_frame>
    <description>The effect of rhlactoferrin on serum levels (picogram/milliliter) of Interleukin-6 (IL-6) will be assessed as a measure of the percentage change of IL-6 serum levels from baseline</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The Effect of Rhlactoferrin on Serum Levels of Tumor Necrosis Factor Alpha Receptor 1 (TNFR1)</measure>
    <time_frame>From baseline to 6 months</time_frame>
    <description>The effect of rhlactoferrin on serum levels (picogram/milliliter) of tumor necrosis factor alpha receptor 1 (TNFR1) assessed as a measure of the percentage change of serum TNFR1 levels from baseline</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Attenuating Cognitive Decline as Measured by the Digital Symbol Substitution Test</measure>
    <time_frame>At 6 months</time_frame>
    <description>The test taker is given a key consisting of numbers 1-9 that are paired with a unique symbol. The test taker is allowed 90 seconds to assign the correct symbol to the number on the list. The test administrator then scores the number of correct answers over the 90 second test time, and assigns a total score based on one point for each correct answer and therefore a higher score is a better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Attenuating Cognitive Decline as Measured by the Trail Making Test A and B.</measure>
    <time_frame>At 6 months</time_frame>
    <description>For test A, the test taker is given a sheet of paper that has the numbers 1-25 within individual circles randomly distributed on the page. The test taker is asked to connect the numbers sequentially over a period of 4 minutes (240 seconds). The score is recorded as the time it takes to complete the task in seconds. For test B, the test taker is given a piece of paper that has numbers 1-13 and letters A-L. Each letter or number is inside of a circle. The test taker must then draw a line from one circled number to the next circled letter (ie. 1 to A to 2 to B to 3 to C etc.) over a period of 6 minutes (360 seconds). The time it takes to complete this task is recorded in seconds.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physical Mobility as Measured by 4 Meter Walk Test</measure>
    <time_frame>At 6 months</time_frame>
    <description>A standard measurement of 4 meters is marked on a flat, long floor surface. The test taker is asked to walk the length at their usual pace while the test giver is recording the time with a stop watch. This test is repeated twice, and the average of the two recorded times is used as the data point.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physical Mobility as Measured by 6 Minute Walk Test</measure>
    <time_frame>At 6 months</time_frame>
    <description>A measured course is set up in an open area on a hard flat surface. The test taker walks on this measured course for 6 minutes, and the test administrators calculates the distance traveled over 6 minutes. The test taker is allowed to rest as is needed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tolerability of Oral rhLactoferrin as Assessed by Patient Diary of Total Number of Side Effects</measure>
    <time_frame>From baseline through 6 months.</time_frame>
    <description>Study coordinators administered side effect questionnaire at each visit and via phone every two weeks during the treatment period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physical Strength as Measured by Grip Strength</measure>
    <time_frame>At 6 months</time_frame>
    <description>Hand grip strength is measured by the amount of static force that the hand can squeeze around a dynamometer. An administrator recorded the reading on the device. The force was measured in kilograms.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Inflammation</condition>
  <condition>Cognitive Deterioration</condition>
  <arm_group>
    <arm_group_label>rhLactoferrin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>rH lactoferrin will be provided by Ventria Biosciences. Each capsule will contain 250 mg of rH lactoferrin as active ingredient. Subjects will receive 1500 mg of lactoferrin in capsule form twice a day. Dosing will be six 250 mg capsules twice a day for six months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Matching placebo capsule will be provided by Ventria Biosciences and six capsules twice a day will be provided to the subjects in this arm.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>rhLactoferrin</intervention_name>
    <description>Eligible participants will be provided with Recombinant Human lactoferrin (rhLF) in 250 mg capsules along with detailed instructions for taking the study drug and they will be asked to take six 250 mg capsules twice a day and to keep a daily dosing dairy.</description>
    <arm_group_label>rhLactoferrin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Eligible participant will be provided with placebo in capsules of 250 mg along with detailed instructions for taking the placebo. Participants will be asked to take six 250 mg capsules twice a day and to keep a daily dosing dairy.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 70 and older&#xD;
&#xD;
          -  able to complete 4- meter timed walk; walking speed &lt;1.0 m/sec&#xD;
&#xD;
          -  serum IL-6 level ≥ 2.5 pg/ml or TNFR1 level ≥1500 pg/ml&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Daily anti-inflammatory drug use (prednisone, Advil, Aleve, Remicade, Enbrel,&#xD;
             methotrexate, standing nonsteroidal anti-inflammatory drugs (NSAID), aspirin greater&#xD;
             than 325 mg per day)&#xD;
&#xD;
          -  lower extremity mobility disability caused by Parkinson's disease,&#xD;
&#xD;
          -  cerebral vascular accident (CVA) with residual motor deficit,&#xD;
&#xD;
          -  severe osteoarthritis or rheumatoid arthritis&#xD;
&#xD;
          -  symptomatic claudication&#xD;
&#xD;
          -  hospitalization within 3 months for myocardial infarction (MI), angina, infection&#xD;
             requiring antibiotics, or joint replacement.&#xD;
&#xD;
          -  Mini-Mental State Examination (MMSE) &lt; 21.&#xD;
&#xD;
          -  Lactose intolerant&#xD;
&#xD;
          -  allergy or intolerance to bovine products&#xD;
&#xD;
          -  being a vegan (since vegans will want to avoid Bovine products.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>70 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jerermy D. Walston, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Johns Hopkins Universtiy</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Jeremy D. Walston</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>November 15, 2016</study_first_submitted>
  <study_first_submitted_qc>November 17, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2016</study_first_posted>
  <results_first_submitted>January 30, 2020</results_first_submitted>
  <results_first_submitted_qc>March 16, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">March 26, 2020</results_first_posted>
  <last_update_submitted>March 16, 2020</last_update_submitted>
  <last_update_submitted_qc>March 16, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 26, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Inflammation</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 15, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/92/NCT02968992/Prot_SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>rhLactoferrin</title>
          <description>rH lactoferrin will be provided by Ventria Biosciences. Each capsule will contain 250 mg of rH lactoferrin as active ingredient. Subjects will receive 1500 mg of lactoferrin in capsule form twice a day. Dosing will be six 250 mg capsules twice a day for six months.&#xD;
rhLactoferrin: Eligible participants will be provided with Recombinant Human lactoferrin (rhLF) in 250 mg capsules along with detailed instructions for taking the study drug and they will be asked to take six 250 mg capsules twice a day and to keep a daily dosing dairy.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Matching placebo capsule will be provided by Ventria Biosciences and six capsules twice a day will be provided to the subjects in this arm.&#xD;
Placebo: Eligible participant will be provided with placebo in capsules of 250 mg along with detailed instructions for taking the placebo. Participants will be asked to take six 250 mg capsules twice a day and to keep a daily dosing dairy.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>rhLactoferrin</title>
          <description>rH lactoferrin will be provided by Ventria Biosciences. Each capsule will contain 250 mg of rH lactoferrin as active ingredient. Subjects will receive 1500 mg of lactoferrin in capsule form twice a day. Dosing will be six 250 mg capsules twice a day for six months.&#xD;
rhLactoferrin: Eligible participants will be provided with Recombinant Human lactoferrin (rhLF) in 250 mg capsules along with detailed instructions for taking the study drug and they will be asked to take six 250 mg capsules twice a day and to keep a daily dosing dairy.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Matching placebo capsule will be provided by Ventria Biosciences and six capsules twice a day will be provided to the subjects in this arm.&#xD;
Placebo: Eligible participant will be provided with placebo in capsules of 250 mg along with detailed instructions for taking the placebo. Participants will be asked to take six 250 mg capsules twice a day and to keep a daily dosing dairy.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="18"/>
            <count group_id="B2" value="18"/>
            <count group_id="B3" value="36"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="18"/>
                    <count group_id="B2" value="18"/>
                    <count group_id="B3" value="36"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <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_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="18"/>
                    <count group_id="B2" value="18"/>
                    <count group_id="B3" value="36"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="82.6" spread="6.6"/>
                    <measurement group_id="B2" value="79.6" spread="5.6"/>
                    <measurement group_id="B3" value="81.1" spread="6.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="18"/>
                    <count group_id="B2" value="18"/>
                    <count group_id="B3" value="36"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="18"/>
                    <count group_id="B2" value="18"/>
                    <count group_id="B3" value="36"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="34"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="18"/>
                    <count group_id="B2" value="18"/>
                    <count group_id="B3" value="36"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>BMI ≥ 30</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="18"/>
                    <count group_id="B2" value="18"/>
                    <count group_id="B3" value="36"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>BMI &lt; 30</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="18"/>
                    <count group_id="B2" value="18"/>
                    <count group_id="B3" value="36"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Physical mobility as measured by 4 meter walk test</title>
          <description>A standard measurement of 4 meters is marked on a flat, long floor surface. The test taker is asked to walk the length at their usual pace while the test giver is recording the time with a stop watch. This test is repeated twice, and the average of the two recorded times is used as the data point.</description>
          <population>A total of 36 participants entered the study. One participant in the placebo group later dropped out and therefore was not included in the analysis.</population>
          <units>m/sec</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="18"/>
                    <count group_id="B2" value="17"/>
                    <count group_id="B3" value="35"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0.78" spread="0.17"/>
                    <measurement group_id="B2" value="0.78" spread="0.13"/>
                    <measurement group_id="B3" value="0.78" spread="0.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Physical strength as measured by grip strength</title>
          <description>Hand grip strength is measured by the amount of static force that the hand can squeeze around a dynamometer. An administrator recorded the reading on the device. The force was measured in kilograms.</description>
          <population>A total of 36 participants entered the study. One participant in the placebo group later dropped out and therefore was not included in the analysis.</population>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="18"/>
                    <count group_id="B2" value="17"/>
                    <count group_id="B3" value="35"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26.2" spread="7.3"/>
                    <measurement group_id="B2" value="25.3" spread="6.7"/>
                    <measurement group_id="B3" value="25.8" spread="6.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Physical mobility as measured by 6 minute walk test</title>
          <description>A measured course is set up in an open area on a hard flat surface. The test taker walks on this measured course for 6 minutes, and the test administrators calculates the distance traveled over 6 minutes. The test taker is allowed to rest as is needed.</description>
          <population>A total of 36 participants entered the study. One participant in the placebo group later dropped out and therefore was not included in the analysis. One participant in the treatment group declined to complete the test.</population>
          <units>meters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="17"/>
                    <count group_id="B2" value="17"/>
                    <count group_id="B3" value="34"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="358.9" spread="124.3"/>
                    <measurement group_id="B2" value="345.8" spread="88.9"/>
                    <measurement group_id="B3" value="352.3" spread="106.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Log Total Activity Count</title>
          <description>Log total activity count was determined using the Acti-Graph® Link Activity monitor which generates a comprehensive assessment of daily free-living activity. Participants wore the monitor for 7 days. Activity counts are proprietary units generated by the Actigraph company software, Actilife. Counts are unitless quantities of physical activity compiled into one-minute intervals across three planes of movement. The vector magnitude of the sum of square of these counts generate the total activity per minute, per hour and per day.</description>
          <population>A total of 36 participants entered the study, one participant in the placebo group later dropped out and therefore was not included in the analysis.</population>
          <units>Log Total Activity Count</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="18"/>
                    <count group_id="B2" value="17"/>
                    <count group_id="B3" value="35"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14.26" spread="0.35"/>
                    <measurement group_id="B2" value="14.46" spread="0.28"/>
                    <measurement group_id="B3" value="14.35" spread="0.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Attenuating cognitive decline as measured by the trail making test A and B</title>
          <description>For test A, the individual is given a sheet of paper that has the numbers 1-25 within individual circles randomly distributed. The individual is asked to connect the numbers sequentially. The score is recorded as the time it takes to complete the task in seconds. For test B, the individual is given a piece of paper that has numbers 1-13 and letters A-L. Each letter or number is inside of a circle. The test taker is instructed to draw a line from one number to the next letter (ie. 1 to A to 2 to B etc.). The score is the seconds it takes to complete the task.</description>
          <population>A total of 36 participants entered the study. One participant in the placebo group later dropped out and therefore was not included in the analysis of test A and test B data. One additional participant in the placebo group was unable to complete Trail Making Test B, so they were not included in the analysis.</population>
          <units>seconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <title>Test A</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="18"/>
                    <count group_id="B2" value="17"/>
                    <count group_id="B3" value="35"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="48.3" spread="16.7"/>
                    <measurement group_id="B2" value="54.1" spread="28.9"/>
                    <measurement group_id="B3" value="51.1" spread="23.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Test B</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="18"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="34"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="101.1" spread="34.6"/>
                    <measurement group_id="B2" value="109.3" spread="49.3"/>
                    <measurement group_id="B3" value="104.9" spread="41.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Attenuating cognitive decline as measured by the digital symbol substitution test</title>
          <description>The test taker is given a key consisting of numbers 1-9 that are paired with a unique symbol. Below the key is a randomly generated list of the numbers repeated several times. The test taker is allowed 90 seconds to assign the correct symbol to the number on the list. The test administrator then scores the number of correct answers over the 90 second test time, and assigns a total score based on one point for each correct answer.</description>
          <population>A total of 36 participants entered the study. One participant in the placebo group later dropped out and therefore was not included in the analysis.</population>
          <units>Correct answers</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="18"/>
                    <count group_id="B2" value="17"/>
                    <count group_id="B3" value="35"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="33" spread="12"/>
                    <measurement group_id="B2" value="31" spread="10"/>
                    <measurement group_id="B3" value="32" spread="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Effect of Rhlactoferrin on Serum Levels of Interleukin-6 (IL-6)</title>
        <description>The effect of rhlactoferrin on serum levels (picogram/milliliter) of Interleukin-6 (IL-6) will be assessed as a measure of the percentage change of IL-6 serum levels from baseline</description>
        <time_frame>Baseline and 6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>rhLactoferrin</title>
            <description>rH lactoferrin will be provided by Ventria Biosciences. Each capsule will contain 250 mg of rH lactoferrin as active ingredient. Subjects will receive 1500 mg of lactoferrin in capsule form twice a day. Dosing will be six 250 mg capsules twice a day for six months.&#xD;
rhLactoferrin: Eligible participants will be provided with Recombinant Human lactoferrin (rhLF) in 250 mg capsules along with detailed instructions for taking the study drug and they will be asked to take six 250 mg capsules twice a day and to keep a daily dosing dairy.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo capsule will be provided by Ventria Biosciences and six capsules twice a day will be provided to the subjects in this arm.&#xD;
Placebo: Eligible participant will be provided with placebo in capsules of 250 mg along with detailed instructions for taking the placebo. Participants will be asked to take six 250 mg capsules twice a day and to keep a daily dosing dairy.</description>
          </group>
        </group_list>
        <measure>
          <title>The Effect of Rhlactoferrin on Serum Levels of Interleukin-6 (IL-6)</title>
          <description>The effect of rhlactoferrin on serum levels (picogram/milliliter) of Interleukin-6 (IL-6) will be assessed as a measure of the percentage change of IL-6 serum levels from baseline</description>
          <units>Percent change of IL-6</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.640" spread="1.137"/>
                    <measurement group_id="O2" value="0.932" spread="0.265"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>The Effect of Rhlactoferrin on Serum Levels of Tumor Necrosis Factor Alpha Receptor 1 (TNFR1)</title>
        <description>The effect of rhlactoferrin on serum levels (picogram/milliliter) of tumor necrosis factor alpha receptor 1 (TNFR1) assessed as a measure of the percentage change of serum TNFR1 levels from baseline</description>
        <time_frame>From baseline to 6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>rhLactoferrin</title>
            <description>rH lactoferrin will be provided by Ventria Biosciences. Each capsule will contain 250 mg of rH lactoferrin as active ingredient. Subjects will receive 1500 mg of lactoferrin in capsule form twice a day. Dosing will be six 250 mg capsules twice a day for six months.&#xD;
rhLactoferrin: Eligible participants will be provided with Recombinant Human lactoferrin (rhLF) in 250 mg capsules along with detailed instructions for taking the study drug and they will be asked to take six 250 mg capsules twice a day and to keep a daily dosing dairy.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo capsule will be provided by Ventria Biosciences and six capsules twice a day will be provided to the subjects in this arm.&#xD;
Placebo: Eligible participant will be provided with placebo in capsules of 250 mg along with detailed instructions for taking the placebo. Participants will be asked to take six 250 mg capsules twice a day and to keep a daily dosing dairy.</description>
          </group>
        </group_list>
        <measure>
          <title>The Effect of Rhlactoferrin on Serum Levels of Tumor Necrosis Factor Alpha Receptor 1 (TNFR1)</title>
          <description>The effect of rhlactoferrin on serum levels (picogram/milliliter) of tumor necrosis factor alpha receptor 1 (TNFR1) assessed as a measure of the percentage change of serum TNFR1 levels from baseline</description>
          <units>Percent change from baseline</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.709" spread="85.084"/>
                    <measurement group_id="O2" value="140.748" spread="43.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Attenuating Cognitive Decline as Measured by the Digital Symbol Substitution Test</title>
        <description>The test taker is given a key consisting of numbers 1-9 that are paired with a unique symbol. The test taker is allowed 90 seconds to assign the correct symbol to the number on the list. The test administrator then scores the number of correct answers over the 90 second test time, and assigns a total score based on one point for each correct answer and therefore a higher score is a better outcome.</description>
        <time_frame>At 6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>rhLactoferrin</title>
            <description>rH lactoferrin will be provided by Ventria Biosciences. Each capsule will contain 250 mg of rH lactoferrin as active ingredient. Subjects will receive 1500 mg of lactoferrin in capsule form twice a day. Dosing will be six 250 mg capsules twice a day for six months.&#xD;
rhLactoferrin: Eligible participants will be provided with Recombinant Human lactoferrin (rhLF) in 250 mg capsules along with detailed instructions for taking the study drug and they will be asked to take six 250 mg capsules twice a day and to keep a daily dosing dairy.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo capsule will be provided by Ventria Biosciences and six capsules twice a day will be provided to the subjects in this arm.&#xD;
Placebo: Eligible participant will be provided with placebo in capsules of 250 mg along with detailed instructions for taking the placebo. Participants will be asked to take six 250 mg capsules twice a day and to keep a daily dosing dairy.</description>
          </group>
        </group_list>
        <measure>
          <title>Attenuating Cognitive Decline as Measured by the Digital Symbol Substitution Test</title>
          <description>The test taker is given a key consisting of numbers 1-9 that are paired with a unique symbol. The test taker is allowed 90 seconds to assign the correct symbol to the number on the list. The test administrator then scores the number of correct answers over the 90 second test time, and assigns a total score based on one point for each correct answer and therefore a higher score is a better outcome.</description>
          <units>correct responses</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.61" lower_limit="26.07" upper_limit="37.16"/>
                    <measurement group_id="O2" value="31" lower_limit="25.42" upper_limit="36.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Attenuating Cognitive Decline as Measured by the Trail Making Test A and B.</title>
        <description>For test A, the test taker is given a sheet of paper that has the numbers 1-25 within individual circles randomly distributed on the page. The test taker is asked to connect the numbers sequentially over a period of 4 minutes (240 seconds). The score is recorded as the time it takes to complete the task in seconds. For test B, the test taker is given a piece of paper that has numbers 1-13 and letters A-L. Each letter or number is inside of a circle. The test taker must then draw a line from one circled number to the next circled letter (ie. 1 to A to 2 to B to 3 to C etc.) over a period of 6 minutes (360 seconds). The time it takes to complete this task is recorded in seconds.</description>
        <time_frame>At 6 months</time_frame>
        <population>A total of 36 participants entered the study. One participant in the placebo group later dropped out and therefore was not included in the analysis. One additional participant in the placebo group was unable to complete Trail Making Test B, so they were not included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>rhLactoferrin</title>
            <description>rH lactoferrin will be provided by Ventria Biosciences. Each capsule will contain 250 mg of rH lactoferrin as active ingredient. Subjects will receive 1500 mg of lactoferrin in capsule form twice a day. Dosing will be six 250 mg capsules twice a day for six months.&#xD;
rhLactoferrin: Eligible participants will be provided with Recombinant Human lactoferrin (rhLF) in 250 mg capsules along with detailed instructions for taking the study drug and they will be asked to take six 250 mg capsules twice a day and to keep a daily dosing dairy.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo capsule will be provided by Ventria Biosciences and six capsules twice a day will be provided to the subjects in this arm.&#xD;
Placebo: Eligible participant will be provided with placebo in capsules of 250 mg along with detailed instructions for taking the placebo. Participants will be asked to take six 250 mg capsules twice a day and to keep a daily dosing dairy.</description>
          </group>
        </group_list>
        <measure>
          <title>Attenuating Cognitive Decline as Measured by the Trail Making Test A and B.</title>
          <description>For test A, the test taker is given a sheet of paper that has the numbers 1-25 within individual circles randomly distributed on the page. The test taker is asked to connect the numbers sequentially over a period of 4 minutes (240 seconds). The score is recorded as the time it takes to complete the task in seconds. For test B, the test taker is given a piece of paper that has numbers 1-13 and letters A-L. Each letter or number is inside of a circle. The test taker must then draw a line from one circled number to the next circled letter (ie. 1 to A to 2 to B to 3 to C etc.) over a period of 6 minutes (360 seconds). The time it takes to complete this task is recorded in seconds.</description>
          <population>A total of 36 participants entered the study. One participant in the placebo group later dropped out and therefore was not included in the analysis. One additional participant in the placebo group was unable to complete Trail Making Test B, so they were not included in the analysis.</population>
          <units>seconds</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Trail Making Test A</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.11" lower_limit="26.36" upper_limit="39.85"/>
                    <measurement group_id="O2" value="42.68" lower_limit="35.89" upper_limit="49.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Trail Making Test B</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="122.73" lower_limit="92.31" upper_limit="153.14"/>
                    <measurement group_id="O2" value="131.24" lower_limit="100.61" upper_limit="161.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Physical Mobility as Measured by 4 Meter Walk Test</title>
        <description>A standard measurement of 4 meters is marked on a flat, long floor surface. The test taker is asked to walk the length at their usual pace while the test giver is recording the time with a stop watch. This test is repeated twice, and the average of the two recorded times is used as the data point.</description>
        <time_frame>At 6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>rhLactoferrin</title>
            <description>rH lactoferrin will be provided by Ventria Biosciences. Each capsule will contain 250 mg of rH lactoferrin as active ingredient. Subjects will receive 1500 mg of lactoferrin in capsule form twice a day. Dosing will be six 250 mg capsules twice a day for six months.&#xD;
rhLactoferrin: Eligible participants will be provided with Recombinant Human lactoferrin (rhLF) in 250 mg capsules along with detailed instructions for taking the study drug and they will be asked to take six 250 mg capsules twice a day and to keep a daily dosing dairy.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo capsule will be provided by Ventria Biosciences and six capsules twice a day will be provided to the subjects in this arm.&#xD;
Placebo: Eligible participant will be provided with placebo in capsules of 250 mg along with detailed instructions for taking the placebo. Participants will be asked to take six 250 mg capsules twice a day and to keep a daily dosing dairy.</description>
          </group>
        </group_list>
        <measure>
          <title>Physical Mobility as Measured by 4 Meter Walk Test</title>
          <description>A standard measurement of 4 meters is marked on a flat, long floor surface. The test taker is asked to walk the length at their usual pace while the test giver is recording the time with a stop watch. This test is repeated twice, and the average of the two recorded times is used as the data point.</description>
          <units>m/sec</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.786" lower_limit="0.701" upper_limit="0.871"/>
                    <measurement group_id="O2" value="0.767" lower_limit="0.681" upper_limit="0.852"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Physical Mobility as Measured by 6 Minute Walk Test</title>
        <description>A measured course is set up in an open area on a hard flat surface. The test taker walks on this measured course for 6 minutes, and the test administrators calculates the distance traveled over 6 minutes. The test taker is allowed to rest as is needed.</description>
        <time_frame>At 6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>rhLactoferrin</title>
            <description>rH lactoferrin will be provided by Ventria Biosciences. Each capsule will contain 250 mg of rH lactoferrin as active ingredient. Subjects will receive 1500 mg of lactoferrin in capsule form twice a day. Dosing will be six 250 mg capsules twice a day for six months.&#xD;
rhLactoferrin: Eligible participants will be provided with Recombinant Human lactoferrin (rhLF) in 250 mg capsules along with detailed instructions for taking the study drug and they will be asked to take six 250 mg capsules twice a day and to keep a daily dosing dairy.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo capsule will be provided by Ventria Biosciences and six capsules twice a day will be provided to the subjects in this arm.&#xD;
Placebo: Eligible participant will be provided with placebo in capsules of 250 mg along with detailed instructions for taking the placebo. Participants will be asked to take six 250 mg capsules twice a day and to keep a daily dosing dairy.</description>
          </group>
        </group_list>
        <measure>
          <title>Physical Mobility as Measured by 6 Minute Walk Test</title>
          <description>A measured course is set up in an open area on a hard flat surface. The test taker walks on this measured course for 6 minutes, and the test administrators calculates the distance traveled over 6 minutes. The test taker is allowed to rest as is needed.</description>
          <units>meter</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="359.66" lower_limit="303.02" upper_limit="416.3"/>
                    <measurement group_id="O2" value="334.94" lower_limit="279.48" upper_limit="390.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tolerability of Oral rhLactoferrin as Assessed by Patient Diary of Total Number of Side Effects</title>
        <description>Study coordinators administered side effect questionnaire at each visit and via phone every two weeks during the treatment period.</description>
        <time_frame>From baseline through 6 months.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>rhLactoferrin</title>
            <description>rH lactoferrin will be provided by Ventria Biosciences. Each capsule will contain 250 mg of rH lactoferrin as active ingredient. Subjects will receive 1500 mg of lactoferrin in capsule form twice a day. Dosing will be six 250 mg capsules twice a day for six months.&#xD;
rhLactoferrin: Eligible participants will be provided with Recombinant Human lactoferrin (rhLF) in 250 mg capsules along with detailed instructions for taking the study drug and they will be asked to take six 250 mg capsules twice a day and to keep a daily dosing dairy.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo capsule will be provided by Ventria Biosciences and six capsules twice a day will be provided to the subjects in this arm.&#xD;
Placebo: Eligible participant will be provided with placebo in capsules of 250 mg along with detailed instructions for taking the placebo. Participants will be asked to take six 250 mg capsules twice a day and to keep a daily dosing dairy.</description>
          </group>
        </group_list>
        <measure>
          <title>Tolerability of Oral rhLactoferrin as Assessed by Patient Diary of Total Number of Side Effects</title>
          <description>Study coordinators administered side effect questionnaire at each visit and via phone every two weeks during the treatment period.</description>
          <units>Side effects/100 treatment days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.23" spread="3.16"/>
                    <measurement group_id="O2" value="4.77" spread="4.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Physical Strength as Measured by Grip Strength</title>
        <description>Hand grip strength is measured by the amount of static force that the hand can squeeze around a dynamometer. An administrator recorded the reading on the device. The force was measured in kilograms.</description>
        <time_frame>At 6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>rhLactoferrin</title>
            <description>rH lactoferrin will be provided by Ventria Biosciences. Each capsule will contain 250 mg of rH lactoferrin as active ingredient. Subjects will receive 1500 mg of lactoferrin in capsule form twice a day. Dosing will be six 250 mg capsules twice a day for six months.&#xD;
rhLactoferrin: Eligible participants will be provided with Recombinant Human lactoferrin (rhLF) in 250 mg capsules along with detailed instructions for taking the study drug and they will be asked to take six 250 mg capsules twice a day and to keep a daily dosing dairy.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo capsule will be provided by Ventria Biosciences and six capsules twice a day will be provided to the subjects in this arm.&#xD;
Placebo: Eligible participant will be provided with placebo in capsules of 250 mg along with detailed instructions for taking the placebo. Participants will be asked to take six 250 mg capsules twice a day and to keep a daily dosing dairy.</description>
          </group>
        </group_list>
        <measure>
          <title>Physical Strength as Measured by Grip Strength</title>
          <description>Hand grip strength is measured by the amount of static force that the hand can squeeze around a dynamometer. An administrator recorded the reading on the device. The force was measured in kilograms.</description>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.493" lower_limit="20.694" upper_limit="26.337"/>
                    <measurement group_id="O2" value="20.294" lower_limit="17.34" upper_limit="23.157"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>6 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>rhLactoferrin</title>
          <description>rH lactoferrin will be provided by Ventria Biosciences. Each capsule will contain 250 mg of rH lactoferrin as active ingredient. Subjects will receive 1500 mg of lactoferrin in capsule form twice a day. Dosing will be six 250 mg capsules twice a day for six months.&#xD;
rhLactoferrin: Eligible participants will be provided with Recombinant Human lactoferrin (rhLF) in 250 mg capsules along with detailed instructions for taking the study drug and they will be asked to take six 250 mg capsules twice a day and to keep a daily dosing dairy.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Matching placebo capsule will be provided by Ventria Biosciences and six capsules twice a day will be provided to the subjects in this arm.&#xD;
Placebo: Eligible participant will be provided with placebo in capsules of 250 mg along with detailed instructions for taking the placebo. Participants will be asked to take six 250 mg capsules twice a day and to keep a daily dosing dairy.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Hospitalization</sub_title>
                <description>Participant suffered an infection from cat bite, which required hospitalization, and he was withdrawn from study</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Loss of Appetite</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Fever/chills</sub_title>
                <description>Fever or chills were associated with respiratory infections</description>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Other conditions</sub_title>
                <description>Other conditions consist of any other medical issues that were not included in the standard side effects.</description>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="18"/>
              </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>The primary limitation of this study was the small sample size.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Jeremy D. Waltson, MD</name_or_title>
      <organization>Johns Hopkins University</organization>
      <phone>410-550-1003</phone>
      <email>jwalston@jhmi.edu</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/NCT02968992
org study id: IRB00094982
nct id: NCT02968992
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to investigate how recombinant human lactoferrin (rhLF) which is
      a partially iron saturated form of lactoferrin produced and purified from rice grain may
      improve mobility and memory in older adults with chronic inflammation. Lactoferrin, is a
      known multifunctional protein, and has been shown to have anti-inflammatory effects. A
      recombinant human version of this protein was recently developed and produced from rice. This
      is now available from the Ventria Bioscience Company in a controlled, pharmaceutical grade
      capsule. As part of this double blinded and randomized study, participants will take daily
      dosages of recombinant human lactoferrin (rhLF) or its matched placebo; to measure the
      effects of rhlactoferrin on chronic inflammation and its association with improving mobility
      and memory over a 6 month time period. During the study all participants will be asked to
      provide blood samples and will have physical and cognitive tests administered to them. By
      measuring biomarkers in the blood as well as changes in physical and cognitive measures, the
      investigators will gain an understanding of how rhlactoferrin may safely improve measures of
      chronic inflammation in older adults. As well as a better understanding of whether it has the
      potential to meaningfully influence important measures of physical and cognitive function
      known to be influenced by Chronic Inflammation (CI).
The primary objective of this study is to examine in a double blinded and randomized trial
      the efficacy of Recombinant Human lactoferrin (rhLF) in reducing chronic inflammation as
      measured by IL-6 and sTNFR1 in the bloodstream. The primary end point is to gather
      information about the tolerability of and adherence to oral rhlactoferrin (rhLF) among older
      adults with CI over a six-month period. The exploratory objective is to assess the efficacy
      of rhlactoferrin (rhLF) in attenuating cognitive decline as measured by the Digit Symbol
      Substitution Test and Trail Making Test, as well as improving physical mobility as measured
      by performance on 4 meter and six-minute walk tests. Further physical and functional
      measurement data will be gather using an Acti-graph link Activity monitor, the raw data
      collected will be used to : (i) characterize cumulative daily activity, (ii) assess daily
      circadian patterns of activity, (iii) assess physical activity variability, (iv) model
      patterns of daily activity, and (iv) estimate walking speed. This additional data will
      complement mobility measures by describing function enacted in daily life
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
masking description: •Randomized: Participants are assigned to intervention groups by chance
measure: The Effect of Rhlactoferrin on Serum Levels of Interleukin-6 (IL-6)
time frame: Baseline and 6 months
description: The effect of rhlactoferrin on serum levels (picogram/milliliter) of Interleukin-6 (IL-6) will be assessed as a measure of the percentage change of IL-6 serum levels from baseline
measure: The Effect of Rhlactoferrin on Serum Levels of Tumor Necrosis Factor Alpha Receptor 1 (TNFR1)
time frame: From baseline to 6 months
description: The effect of rhlactoferrin on serum levels (picogram/milliliter) of tumor necrosis factor alpha receptor 1 (TNFR1) assessed as a measure of the percentage change of serum TNFR1 levels from baseline
measure: Attenuating Cognitive Decline as Measured by the Digital Symbol Substitution Test
time frame: At 6 months
description: The test taker is given a key consisting of numbers 1-9 that are paired with a unique symbol. The test taker is allowed 90 seconds to assign the correct symbol to the number on the list. The test administrator then scores the number of correct answers over the 90 second test time, and assigns a total score based on one point for each correct answer and therefore a higher score is a better outcome.
measure: Attenuating Cognitive Decline as Measured by the Trail Making Test A and B.
time frame: At 6 months
description: For test A, the test taker is given a sheet of paper that has the numbers 1-25 within individual circles randomly distributed on the page. The test taker is asked to connect the numbers sequentially over a period of 4 minutes (240 seconds). The score is recorded as the time it takes to complete the task in seconds. For test B, the test taker is given a piece of paper that has numbers 1-13 and letters A-L. Each letter or number is inside of a circle. The test taker must then draw a line from one circled number to the next circled letter (ie. 1 to A to 2 to B to 3 to C etc.) over a period of 6 minutes (360 seconds). The time it takes to complete this task is recorded in seconds.
measure: Physical Mobility as Measured by 4 Meter Walk Test
time frame: At 6 months
description: A standard measurement of 4 meters is marked on a flat, long floor surface. The test taker is asked to walk the length at their usual pace while the test giver is recording the time with a stop watch. This test is repeated twice, and the average of the two recorded times is used as the data point.
measure: Physical Mobility as Measured by 6 Minute Walk Test
time frame: At 6 months
description: A measured course is set up in an open area on a hard flat surface. The test taker walks on this measured course for 6 minutes, and the test administrators calculates the distance traveled over 6 minutes. The test taker is allowed to rest as is needed.
measure: Tolerability of Oral rhLactoferrin as Assessed by Patient Diary of Total Number of Side Effects
time frame: From baseline through 6 months.
description: Study coordinators administered side effect questionnaire at each visit and via phone every two weeks during the treatment period.
measure: Physical Strength as Measured by Grip Strength
time frame: At 6 months
description: Hand grip strength is measured by the amount of static force that the hand can squeeze around a dynamometer. An administrator recorded the reading on the device. The force was measured in kilograms.
arm group label: rhLactoferrin
arm group type: Experimental
description: rH lactoferrin will be provided by Ventria Biosciences. Each capsule will contain 250 mg of rH lactoferrin as active ingredient. Subjects will receive 1500 mg of lactoferrin in capsule form twice a day. Dosing will be six 250 mg capsules twice a day for six months.
arm group label: Placebo
arm group type: Placebo Comparator
description: Matching placebo capsule will be provided by Ventria Biosciences and six capsules twice a day will be provided to the subjects in this arm.
intervention type: Drug
intervention name: rhLactoferrin
description: Eligible participants will be provided with Recombinant Human lactoferrin (rhLF) in 250 mg capsules along with detailed instructions for taking the study drug and they will be asked to take six 250 mg capsules twice a day and to keep a daily dosing dairy.
arm group label: rhLactoferrin
intervention type: Other
intervention name: Placebo
description: Eligible participant will be provided with placebo in capsules of 250 mg along with detailed instructions for taking the placebo. Participants will be asked to take six 250 mg capsules twice a day and to keep a daily dosing dairy.
arm group label: Placebo
criteria: 
gender: All
minimum age: 70 Years
maximum age: N/A
healthy volunteers: No
last name: Jerermy D. Walston, MD
role: Principal Investigator
affiliation: Johns Hopkins Universtiy
facility: 
country: United States
responsible party type: Sponsor
mesh term: Inflammation
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The primary limitation of this study was the small sample size.
point of contact: 