<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/NCT03825042</url>
  </required_header>
  <id_info>
    <org_study_id>MEIF/17/BAC-COG/001</org_study_id>
    <nct_id>NCT03825042</nct_id>
  </id_info>
  <brief_title>Effect of an Antioxidants Mix on Cognitive Performance and Well Being: The Bacopa, Licopene, Astaxantina, Vitamin B12</brief_title>
  <acronym>BLAtwelve</acronym>
  <official_title>Effect of an Antioxidants Mix on Cognitive Performance and Well Being: The Bacopa, Licopene, Astaxantina, Vitamin B12</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>A. Menarini Industrie Farmaceutiche Riunite S.r.l.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>A. Menarini Industrie Farmaceutiche Riunite S.r.l.</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>
      Nine-weeks double-blind, randomized, placebo-controlled, parallel-arm superiority study.&#xD;
&#xD;
      The aim of this study is to evaluate the influence of a mix of four bioactive compounds -&#xD;
      bacopa, lycopene, astaxanthin and vitamin B12 - on cognitive performance, mood state and&#xD;
      well-being in subjects aged ≥ 60 years with no evidence of cognitive dysfunction.&#xD;
&#xD;
      The primary objective of the study is to evaluate the changes in Trial Making Test (TMT)&#xD;
      scores from baseline (V2) to 8 weeks of treatment (V4), analyzed in the following&#xD;
      hierarchical order: TMT-B, TMT-A and TMT B-A.&#xD;
&#xD;
      Secondary objectives of this study are to evaluate changes from baseline (V2) to 8 weeks of&#xD;
      treatment (V4) in Verbal Fluency Test (VFT) score, Montreal Cognitive Assessment (MoCA)&#xD;
      score, Mini Mental State Examination (MMSE) score, Rey Auditory Verbal Learning Test (AVLT),&#xD;
      psychological well-being as assessed by General Health Questionnaire (GHQ-12), mood states as&#xD;
      assessed by the Profile of Mood Stated (POMS), sexual satisfaction as evaluated by the New&#xD;
      Sexual Satisfaction Scale (NSSS).&#xD;
&#xD;
      Changes of metabolic parameters from baseline (V2) to 4 weeks of treatment (V3) and from&#xD;
      baseline (V2) to 8 weeks of treatment (V4) will be also evaluated as secondary objectives&#xD;
      (glucose, insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), total&#xD;
      cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, uric acid).&#xD;
&#xD;
      Changes of plasma markers of oxidative stress from baseline (V2) to 4 weeks of treatment (V3)&#xD;
      and from baseline (V2) to 8 weeks of treatment (V4) will be evaluated as secondary objectives&#xD;
      (8-iso-Prostaglandin F2alpha, Plasma malondialdehyde).&#xD;
&#xD;
      Finally the safety and tolerability of the study product will be assessed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study has been conducted in 1 Italian clinical site and involved 80 subjects.&#xD;
&#xD;
      Subjects will be randomly allocated to one of the following groups:&#xD;
&#xD;
        -  Group I: mix of the four bioactive compounds (bacopa, lycopene, astaxanthin and vitamin&#xD;
           B12), once a day for 8 weeks per os;&#xD;
&#xD;
        -  Group II: placebo, once a day for 8 weeks per os.&#xD;
&#xD;
      The study is double blind. Neither the study staff at clinical sites (Investigators, nurses,&#xD;
      pharmacist) nor the subject was aware of the treatment assigned.&#xD;
&#xD;
      Each participant attended 4 visits over a total period of about 9 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 23, 2018</start_date>
  <completion_date type="Actual">October 29, 2018</completion_date>
  <primary_completion_date type="Actual">October 29, 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>9-weeks double-blind, randomized, placebo-controlled, parallel-arm superiority study</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>The study treatment was assigned through envelopes randomization system: the site was provided with sealed envelopes, numbered in progressive number starting from R-001, containing the treatment kit to be assigned to the subject. The Investigator will open the first available envelope in progressive order. Inside the envelope there will be the kit number of the treatment to be assigned to that subject.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Trail Making Test (TMT) B Between Baseline and End of Treatment</measure>
    <time_frame>8 weeks - from baseline to end of study</time_frame>
    <description>Change in Trail Making Test (TMT) B scores from baseline (V2) to 8 weeks of treatment (V4).&#xD;
The reduction in the number of seconds the patients take to make the test after the study treatment means an improvement in cognitive functions.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change Trail Making Test (TMT) A Between Baseline and End of Treatment</measure>
    <time_frame>8 weeks - from baseline to end of study</time_frame>
    <description>Change in Trail Making Test (TMT) A scores from baseline (V2) to 8 weeks of treatment (V4).&#xD;
The reduction in the number of seconds the patients take to make the test after the study treatment means an improvement in cognitive functions.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Trail Making Test (TMT) B - Trail Making Test (TMT) A Between Baseline and End of Treatment</measure>
    <time_frame>8 weeks - from baseline to end of study</time_frame>
    <description>Change in Trail Making Test (TMT) B score minus Trail Making Test (TMT) A score from baseline (V2) to 8 weeks of treatment (V4).&#xD;
The reduction in the number of seconds the patients take to make the test after the study treatment means an improvement in cognitive functions.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">80</enrollment>
  <condition>Cognitive Dysfunction</condition>
  <arm_group>
    <arm_group_label>Food supplement</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A mix of bacopa, lycopene, astaxanthin and vitamin B12 Dosage form: tablets Dosage: 1 tablet/die Duration: 8 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Inactive compound Dosage form: tablets Dosage: 1 tablet/die Duration: 8 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>A mix of bioactive natural compounds</intervention_name>
    <description>A mix of bacopa, lycopene, astaxanthin and vitamin B12 in oral tablets</description>
    <arm_group_label>Food supplement</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Inactive compound in oral tablets</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subjects aged ≥60 years.&#xD;
&#xD;
          2. Subjects who provide written Informed Consent to the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects with cognitive dysfunctions or clinically significant coexisting medical&#xD;
             conditions (cardiovascular disease, cerebrovascular events, overt dementia defined by&#xD;
             MMSE &lt;27 or other neurological disorders, thyroid disorders, or inflammatory diseases)&#xD;
&#xD;
          2. Subjects with a score on the Geriatric Depression Scale (GDS) &gt;11 in order to avoid&#xD;
             confounding due to the influence of concomitant depression on the performance on&#xD;
             cognitive tests&#xD;
&#xD;
          3. Current smokers&#xD;
&#xD;
          4. Habitual users of antioxidant supplements (including vitamins C and E)&#xD;
&#xD;
          5. Habitual consumers of chocolate or other cocoa products (daily consumption of any&#xD;
             amount)&#xD;
&#xD;
          6. Subjects under treatments with medications known to have antioxidant properties&#xD;
             (including statins and glitazones) or to interfere with cognitive functions (including&#xD;
             benzodiazepines and antidepressants)&#xD;
&#xD;
          7. Subjects with hypersensitivity to any component of the study medications&#xD;
&#xD;
          8. Subjects who are participating in or having participated in another clinical trial&#xD;
             within the previous three months.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Giovambattista GD Desideri</last_name>
    <role>Principal Investigator</role>
    <affiliation>U.O.C. Geriatria e Lungodegenza - P.O. SS Filippo e Nicola di Avezzano</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>U.O.C. Geriatria e Lungodegenza - P.O. SS Filippo e Nicola di Avezzano</name>
      <address>
        <city>Avezzano</city>
        <state>L'Aquila</state>
        <zip>67051</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>January 30, 2019</study_first_submitted>
  <study_first_submitted_qc>January 30, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 31, 2019</study_first_posted>
  <results_first_submitted>August 22, 2019</results_first_submitted>
  <results_first_submitted_qc>July 9, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">July 27, 2020</results_first_posted>
  <last_update_submitted>July 9, 2020</last_update_submitted>
  <last_update_submitted_qc>July 9, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 27, 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>Cognitive Dysfunction</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 11, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/42/NCT03825042/SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>October 9, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/42/NCT03825042/Prot_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The recruitment period started on January 2018 and terminated on October 2018. A total of 80 subjetcs have been randomization and 78 completed the study. Each subject has been involved in the study for approximately two months. A total of 4 study visits has been performed for each subject.</recruitment_details>
      <pre_assignment_details>Subjects who provided written informed consent have been subjected to the screening assessments. Subjects who met all inclusion criteria and none of the exclusion criteria have been eligible for the study and have proceeded with the randomization visit after 7 days.&#xD;
No wash-out or run-in period was used in this study. 8</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Food Supplement</title>
          <description>A mix of bacopa, lycopene, astaxanthin and vitamin B12 Dosage form: tablets Dosage: 1 tablet per day Duration: 8 weeks&#xD;
A mix of bioactive natural compounds: A mix of bacopa, lycopene, astaxanthin and vitamin B12 in oral tablets</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Inactive compound Dosage form: tablets Dosage: 1 tablet per day Duration: 8 weeks&#xD;
Placebo: Inactive compound in oral tablets</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="40"/>
                <participants group_id="P2" count="40"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="38"/>
                <participants group_id="P2" count="40"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Food Supplement</title>
          <description>A mix of bacopa, lycopene, astaxanthin and vitamin B12 Dosage form: tablets Dosage: 1 tablet per day Duration: 8 weeks&#xD;
A mix of bioactive natural compounds: A mix of bacopa, lycopene, astaxanthin and vitamin B12 in oral tablets</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Inactive compound Dosage form: tablets Dosage: 1 tablet per day Duration: 8 weeks&#xD;
Placebo: Inactive compound in oral tablets</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="40"/>
            <count group_id="B2" value="40"/>
            <count group_id="B3" value="80"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="37"/>
                    <measurement group_id="B2" value="39"/>
                    <measurement group_id="B3" value="76"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                  </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>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61.88" spread="1.36"/>
                    <measurement group_id="B2" value="62.05" spread="1.55"/>
                    <measurement group_id="B3" value="61.96" spread="1.45"/>
                  </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>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="55"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="25"/>
                  </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>
              <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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                    <measurement group_id="B2" value="40"/>
                    <measurement group_id="B3" value="80"/>
                  </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>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Italy</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                    <measurement group_id="B2" value="40"/>
                    <measurement group_id="B3" value="80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Trial Making Test (TMT) A</title>
          <description>TMT, which explores visual-conceptual and visual-motor tracking, is a frequently used neuropsychological test because of its sensitivity to brain damage. TMT is administered in two parts: TMT-A and TMT-B.&#xD;
Part A is a visual-scanning, timed task where participants are asked to connect with lines 25 circles numbered from 1 to 25 as quickly as possible. The test is terminated after 5 minutes even if not completed.</description>
          <units>seconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25.17" spread="10.53"/>
                    <measurement group_id="B2" value="24.20" spread="7.37"/>
                    <measurement group_id="B3" value="24.68" spread="8.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Trial Making Test (TMT) B</title>
          <description>TMT, which explores visual-conceptual and visual-motor tracking, is a frequently used neuropsychological test because of its sensitivity to brain damage. TMT is administered in two parts: TMT-A and TMT-B.&#xD;
In Part B participants are asked to connect circles containing numbers (from 1 to 13) or letters (from A to L) in an alternate numeric/alphabetical order. The test is terminated in every case after 10 minutes even if not completed.</description>
          <units>seconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="56.97" spread="25.37"/>
                    <measurement group_id="B2" value="54.64" spread="21.30"/>
                    <measurement group_id="B3" value="55.80" spread="23.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Trail Making Test (TMT) B Between Baseline and End of Treatment</title>
        <description>Change in Trail Making Test (TMT) B scores from baseline (V2) to 8 weeks of treatment (V4).&#xD;
The reduction in the number of seconds the patients take to make the test after the study treatment means an improvement in cognitive functions.</description>
        <time_frame>8 weeks - from baseline to end of study</time_frame>
        <population>Intention To Treat</population>
        <group_list>
          <group group_id="O1">
            <title>Food Supplement</title>
            <description>A mix of bacopa, lycopene, astaxanthin and vitamin B12 Dosage form: tablets Dosage: 1 tablet per day Duration: 8 weeks&#xD;
A mix of bioactive natural compounds: A mix of bacopa, lycopene, astaxanthin and vitamin B12 in oral tablets</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Inactive compound Dosage form: tablets Dosage: 1 tablet per day Duration: 8 weeks&#xD;
Placebo: Inactive compound in oral tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Trail Making Test (TMT) B Between Baseline and End of Treatment</title>
          <description>Change in Trail Making Test (TMT) B scores from baseline (V2) to 8 weeks of treatment (V4).&#xD;
The reduction in the number of seconds the patients take to make the test after the study treatment means an improvement in cognitive functions.</description>
          <population>Intention To Treat</population>
          <units>seconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="38"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-17.63" spread="18.93"/>
                    <measurement group_id="O2" value="3.46" spread="13.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0000</p_value>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-21.01</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-26.80</ci_lower_limit>
            <ci_upper_limit>-15.20</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change Trail Making Test (TMT) A Between Baseline and End of Treatment</title>
        <description>Change in Trail Making Test (TMT) A scores from baseline (V2) to 8 weeks of treatment (V4).&#xD;
The reduction in the number of seconds the patients take to make the test after the study treatment means an improvement in cognitive functions.</description>
        <time_frame>8 weeks - from baseline to end of study</time_frame>
        <population>Intention To Treat</population>
        <group_list>
          <group group_id="O1">
            <title>Food Supplement</title>
            <description>A mix of bacopa, lycopene, astaxanthin and vitamin B12 Dosage form: tablets Dosage: 1 tablet per day Duration: 8 weeks&#xD;
A mix of bioactive natural compounds: A mix of bacopa, lycopene, astaxanthin and vitamin B12 in oral tablets</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Inactive compound Dosage form: tablets Dosage: 1 tablet per day Duration: 8 weeks&#xD;
Placebo: Inactive compound in oral tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Change Trail Making Test (TMT) A Between Baseline and End of Treatment</title>
          <description>Change in Trail Making Test (TMT) A scores from baseline (V2) to 8 weeks of treatment (V4).&#xD;
The reduction in the number of seconds the patients take to make the test after the study treatment means an improvement in cognitive functions.</description>
          <population>Intention To Treat</population>
          <units>seconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="38"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.86" spread="10.00"/>
                    <measurement group_id="O2" value="-0.37" spread="5.31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0000</p_value>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-6.08</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-8.45</ci_lower_limit>
            <ci_upper_limit>-3.61</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Trail Making Test (TMT) B - Trail Making Test (TMT) A Between Baseline and End of Treatment</title>
        <description>Change in Trail Making Test (TMT) B score minus Trail Making Test (TMT) A score from baseline (V2) to 8 weeks of treatment (V4).&#xD;
The reduction in the number of seconds the patients take to make the test after the study treatment means an improvement in cognitive functions.</description>
        <time_frame>8 weeks - from baseline to end of study</time_frame>
        <population>Intention To Treat</population>
        <group_list>
          <group group_id="O1">
            <title>Food Supplement</title>
            <description>A mix of bacopa, lycopene, astaxanthin and vitamin B12 Dosage form: tablets Dosage: 1 tablet per day Duration: 8 weeks&#xD;
A mix of bioactive natural compounds: A mix of bacopa, lycopene, astaxanthin and vitamin B12 in oral tablets</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Inactive compound Dosage form: tablets Dosage: 1 tablet per day Duration: 8 weeks&#xD;
Placebo: Inactive compound in oral tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Trail Making Test (TMT) B - Trail Making Test (TMT) A Between Baseline and End of Treatment</title>
          <description>Change in Trail Making Test (TMT) B score minus Trail Making Test (TMT) A score from baseline (V2) to 8 weeks of treatment (V4).&#xD;
The reduction in the number of seconds the patients take to make the test after the study treatment means an improvement in cognitive functions.</description>
          <population>Intention To Treat</population>
          <units>seconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="38"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.46" spread="16.62"/>
                    <measurement group_id="O2" value="3.84" spread="11.65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0000</p_value>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-14.56</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-20.02</ci_lower_limit>
            <ci_upper_limit>-9.11</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>8 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Food Supplement</title>
          <description>A mix of bacopa, lycopene, astaxanthin and vitamin B12 Dosage form: tablets Dosage: 1 tablet per day Duration: 8 weeks&#xD;
A mix of bioactive natural compounds: A mix of bacopa, lycopene, astaxanthin and vitamin B12 in oral tablets</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Inactive compound Dosage form: tablets Dosage: 1 tablet per day Duration: 8 weeks&#xD;
Placebo: Inactive compound in oral tablets</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 21.1</default_vocab>
        <default_assessment>Non-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="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Hepatitis E</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 21.1</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="40"/>
              </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>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Director of Clinical Operations</name_or_title>
      <organization>A.Menarini Industrie Farmaceutiche Riunite Srl</organization>
      <phone>0039 055 5680459</phone>
      <email>pfabrizzi@menarini.it</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/NCT03825042
org study id: MEIF/17/BAC-COG/001
nct id: NCT03825042
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Nine-weeks double-blind, randomized, placebo-controlled, parallel-arm superiority study.

      The aim of this study is to evaluate the influence of a mix of four bioactive compounds -
      bacopa, lycopene, astaxanthin and vitamin B12 - on cognitive performance, mood state and
      well-being in subjects aged ≥ 60 years with no evidence of cognitive dysfunction.

      The primary objective of the study is to evaluate the changes in Trial Making Test (TMT)
      scores from baseline (V2) to 8 weeks of treatment (V4), analyzed in the following
      hierarchical order: TMT-B, TMT-A and TMT B-A.

      Secondary objectives of this study are to evaluate changes from baseline (V2) to 8 weeks of
      treatment (V4) in Verbal Fluency Test (VFT) score, Montreal Cognitive Assessment (MoCA)
      score, Mini Mental State Examination (MMSE) score, Rey Auditory Verbal Learning Test (AVLT),
      psychological well-being as assessed by General Health Questionnaire (GHQ-12), mood states as
      assessed by the Profile of Mood Stated (POMS), sexual satisfaction as evaluated by the New
      Sexual Satisfaction Scale (NSSS).

      Changes of metabolic parameters from baseline (V2) to 4 weeks of treatment (V3) and from
      baseline (V2) to 8 weeks of treatment (V4) will be also evaluated as secondary objectives
      (glucose, insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), total
      cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, uric acid).

      Changes of plasma markers of oxidative stress from baseline (V2) to 4 weeks of treatment (V3)
      and from baseline (V2) to 8 weeks of treatment (V4) will be evaluated as secondary objectives
      (8-iso-Prostaglandin F2alpha, Plasma malondialdehyde).

      Finally the safety and tolerability of the study product will be assessed.
The study has been conducted in 1 Italian clinical site and involved 80 subjects.

      Subjects will be randomly allocated to one of the following groups:

        -  Group I: mix of the four bioactive compounds (bacopa, lycopene, astaxanthin and vitamin
           B12), once a day for 8 weeks per os;

        -  Group II: placebo, once a day for 8 weeks per os.

      The study is double blind. Neither the study staff at clinical sites (Investigators, nurses,
      pharmacist) nor the subject was aware of the treatment assigned.

      Each participant attended 4 visits over a total period of about 9 weeks.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: 9-weeks double-blind, randomized, placebo-controlled, parallel-arm superiority study
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: The study treatment was assigned through envelopes randomization system: the site was provided with sealed envelopes, numbered in progressive number starting from R-001, containing the treatment kit to be assigned to the subject. The Investigator will open the first available envelope in progressive order. Inside the envelope there will be the kit number of the treatment to be assigned to that subject.
measure: Change in Trail Making Test (TMT) B Between Baseline and End of Treatment
time frame: 8 weeks - from baseline to end of study
description: Change in Trail Making Test (TMT) B scores from baseline (V2) to 8 weeks of treatment (V4).
The reduction in the number of seconds the patients take to make the test after the study treatment means an improvement in cognitive functions.
measure: Change Trail Making Test (TMT) A Between Baseline and End of Treatment
time frame: 8 weeks - from baseline to end of study
description: Change in Trail Making Test (TMT) A scores from baseline (V2) to 8 weeks of treatment (V4).
The reduction in the number of seconds the patients take to make the test after the study treatment means an improvement in cognitive functions.
measure: Change in Trail Making Test (TMT) B - Trail Making Test (TMT) A Between Baseline and End of Treatment
time frame: 8 weeks - from baseline to end of study
description: Change in Trail Making Test (TMT) B score minus Trail Making Test (TMT) A score from baseline (V2) to 8 weeks of treatment (V4).
The reduction in the number of seconds the patients take to make the test after the study treatment means an improvement in cognitive functions.
arm group label: Food supplement
arm group type: Experimental
description: A mix of bacopa, lycopene, astaxanthin and vitamin B12 Dosage form: tablets Dosage: 1 tablet/die Duration: 8 weeks
arm group label: Placebo
arm group type: Placebo Comparator
description: Inactive compound Dosage form: tablets Dosage: 1 tablet/die Duration: 8 weeks
intervention type: Dietary Supplement
intervention name: A mix of bioactive natural compounds
description: A mix of bacopa, lycopene, astaxanthin and vitamin B12 in oral tablets
arm group label: Food supplement
intervention type: Dietary Supplement
intervention name: Placebo
description: Inactive compound in oral tablets
arm group label: Placebo
criteria: 
gender: All
minimum age: 60 Years
maximum age: N/A
healthy volunteers: No
last name: Giovambattista GD Desideri
role: Principal Investigator
affiliation: U.O.C. Geriatria e Lungodegenza - P.O. SS Filippo e Nicola di Avezzano
facility: 
country: Italy
responsible party type: Sponsor
mesh term: Cognitive Dysfunction
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 