<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/NCT03820245</url>
  </required_header>
  <id_info>
    <org_study_id>68801917.0.0000.5346</org_study_id>
    <nct_id>NCT03820245</nct_id>
  </id_info>
  <brief_title>Effect of Short-term Annatto Carotenoids Supplementation on Oxidative Stress Status in Healthy Individuals</brief_title>
  <official_title>Short-term Annatto Carotenoids Supplementation Effect on LDL Susceptibility to Ex-vivo Oxidation and Oxidative Stress Biomarkers in Healthy Individuals</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universidade Federal de Santa Maria</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Universidade Federal de Santa Maria</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Low-density lipoprotein (LDL) oxidation has a pivotal role in atherosclerosis development.&#xD;
      There is a relationship between carotenoids serum concentration and cardiovascular (CV)&#xD;
      benefits, mainly in oxidized LDL (oxLDL) reduction. Despite cardio protective effects of&#xD;
      annatto carotenoids, bixin and norbixin, in vitro and in animal studies, its short or&#xD;
      long-term supplementation effect on humans are not know. Objective: To analyse CV benefits of&#xD;
      annatto carotenoids short-term supplementation in healthy individuals, comparing to lycopene&#xD;
      effect. Methods: 16 healthy volunteers (8 men and 8 women) consumed 0.05 mg/kg b.w. of each&#xD;
      treatment (bixin, norbixin, lycopene or placebo) through capsules, during 7 days. It was&#xD;
      analysed the susceptibility of LDL to Cu2+-induced oxidation, biochemical parameters and&#xD;
      oxidative stress biomarkers at the beginning and end of each treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Graduate and post-graduate students were recruited in Federal University of Santa Maria to&#xD;
      study participation. First, the health status of volunteers was analysed by questioner&#xD;
      application (to evaluate lifestyle, family history, individual characteristics),&#xD;
      anthropometric (height, weight, waist circumference) and biochemical parameters (glucose,&#xD;
      lipid profile, transaminases, urea, creatinine) measurements. According to inclusion&#xD;
      criteria, 18 volunteers were able to study participation, but just 16 people remained until&#xD;
      the end of the study.&#xD;
&#xD;
      Each treatment was composed by 7 capsules (containing 0.05 mg carotenoid or placebo/kg b.w.)&#xD;
      which should be consumed once a day (preferably in the morning), during 7 days. It was&#xD;
      conducted a randomized, double blind, placebo-controlled crossover clinical trial, where 16&#xD;
      participants received 4 proposed treatments (bixin, norbixin, lycopene and placebo) in&#xD;
      different periods. To plasma, serum and red blood cells (RBC) obtainment, 2 fasting blood&#xD;
      collections were made, in the beginning (Day 0) and the end (Day 7) of each treatment. These&#xD;
      samples were used for evaluating the ex vivo oxidation of LDL induced by copper sulphate and&#xD;
      biochemical and oxidative biomarkers measurements.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 24, 2016</start_date>
  <completion_date type="Actual">July 25, 2018</completion_date>
  <primary_completion_date type="Actual">April 15, 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>Crossover Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>Double blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Evaluation of LDL lipid moiety susceptibility to copper induced oxidation - oxidation rate</measure>
    <time_frame>Day 0 and Day 7</time_frame>
    <description>Change (Day 7 - Day 0) of oxidation rate of conjugated dienes formed after copper sulphate addition to LDL particles</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Evaluation of LDL protein moiety susceptibility to copper induced oxidation</measure>
    <time_frame>Day 0 and Day 7</time_frame>
    <description>Evaluate the change (Day 7 - Day 0) of loss of tryptophan fluorescence after oxidation induced by copper</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Evaluation of LDL lipid moiety susceptibility to copper induced oxidation - lag phase</measure>
    <time_frame>Day 0 and Day 7</time_frame>
    <description>Change (Day 7 - Day 0) of lag phase time of conjugated dienes formed after copper sulphate addition to LDL particles</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluation of protein oxidation</measure>
    <time_frame>Day 0 and Day 7</time_frame>
    <description>Change at advanced oxidation protein products levels in plasma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of lipid oxidation</measure>
    <time_frame>Day 0 and Day 7</time_frame>
    <description>Change at malondialdehyde levels in plasma and red blood cells</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of nitric oxide metabolites</measure>
    <time_frame>Day 0 and Day 7</time_frame>
    <description>Change at nitric oxide metabolites levels in serum</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of plasma antioxidant capacity</measure>
    <time_frame>Day 0 and Day 7</time_frame>
    <description>Change at oxygen radical absorbance capacity in plasma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of enzymatic antioxidant defences</measure>
    <time_frame>Day 0 and Day 7</time_frame>
    <description>Change at antioxidant enzymes activities in red blood cells</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of gluthatione cycle</measure>
    <time_frame>Day 0 and Day 7</time_frame>
    <description>Change at reduced glutathione/oxidized glutathione ratio in red blood cells</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of red blood cell osmotic fragility</measure>
    <time_frame>Day 7</time_frame>
    <description>Change of red blood cell osmotic fragility after ex vivo exposure to membrane damage inducers</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of carotenoids levels</measure>
    <time_frame>Day 0 and Day 7</time_frame>
    <description>Change at carotenoids levels in plasma and red blood cells</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Oxidative Stress</condition>
  <condition>Atherosclerosis</condition>
  <arm_group>
    <arm_group_label>Bixin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Consumption of 0.05 mg bixin/kg b.w. through capsules (once a day) by 7 days in the morning.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Norbixin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Consumption of 0.05 mg norbixin/kg b.w. through capsules (once a day) by 7 days in the morning.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Lycopene</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Consumption of 0.05 mg lycopene/kg b.w. through capsules (once a day) by 7 days in the morning.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Consumption of 0.05 mg placebo/kg b.w. through capsules (once a day) by 7 days in the morning.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Bixin</intervention_name>
    <description>Volunteers consumed bixin capsules during 1 week , maintaining their usal lifestyle (avoiding excessive/unusual of fat and carotenoid-containing food, alcohol)</description>
    <arm_group_label>Bixin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Norbixin</intervention_name>
    <description>Volunteers consumed norbixin capsules during 1 week , maintaining their usal lifestyle (avoiding excessive/unusual of fat and carotenoid-containing food, alcohol)</description>
    <arm_group_label>Norbixin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Lycopene</intervention_name>
    <description>Volunteers consumed lycopene capsules during 1 week , maintaining their usal lifestyle (avoiding excessive/unusual of fat and carotenoid-containing food, alcohol)</description>
    <arm_group_label>Lycopene</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Volunteers consumed placebo capsules during 1 week , maintaining their usal lifestyle (avoiding excessive/unusual of fat and carotenoid-containing food, alcohol)</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Normal levels of glucose, lipid profile, transaminases, urea and creatine&#xD;
&#xD;
          -  Normal blood pressure, weight and body mass index (BMI)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Chronic diseases (diabetes, dyslipiademia, hypertension cancer, etc.)&#xD;
&#xD;
          -  Drug, alcohol and cigarette consumption/addiction&#xD;
&#xD;
          -  Medication, vitamins or suplements consumption (except oral contraceptive used by&#xD;
             women)&#xD;
&#xD;
          -  Recent inflammatory/infectious diseases&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tatiana Emanuelli, Doctor</last_name>
    <role>Study Director</role>
    <affiliation>Universidade Federal de Santa Maria</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Universidade Federal de Santa Maria</name>
      <address>
        <city>Santa Maria</city>
        <state>Rio Grande Do Sul</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>October 19, 2018</study_first_submitted>
  <study_first_submitted_qc>January 25, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 29, 2019</study_first_posted>
  <last_update_submitted>December 27, 2019</last_update_submitted>
  <last_update_submitted_qc>December 27, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 2, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Universidade Federal de Santa Maria</investigator_affiliation>
    <investigator_full_name>Lisiane Conte</investigator_full_name>
    <investigator_title>Master's degree student</investigator_title>
  </responsible_party>
  <keyword>Carotenoid</keyword>
  <keyword>LDL oxidation</keyword>
  <keyword>Cardiovascular disease</keyword>
  <keyword>Antioxidant</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atherosclerosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lycopene</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Data may be shared after article publication.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03820245
org study id: 68801917.0.0000.5346
nct id: NCT03820245
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Low-density lipoprotein (LDL) oxidation has a pivotal role in atherosclerosis development.
      There is a relationship between carotenoids serum concentration and cardiovascular (CV)
      benefits, mainly in oxidized LDL (oxLDL) reduction. Despite cardio protective effects of
      annatto carotenoids, bixin and norbixin, in vitro and in animal studies, its short or
      long-term supplementation effect on humans are not know. Objective: To analyse CV benefits of
      annatto carotenoids short-term supplementation in healthy individuals, comparing to lycopene
      effect. Methods: 16 healthy volunteers (8 men and 8 women) consumed 0.05 mg/kg b.w. of each
      treatment (bixin, norbixin, lycopene or placebo) through capsules, during 7 days. It was
      analysed the susceptibility of LDL to Cu2+-induced oxidation, biochemical parameters and
      oxidative stress biomarkers at the beginning and end of each treatment.
Graduate and post-graduate students were recruited in Federal University of Santa Maria to
      study participation. First, the health status of volunteers was analysed by questioner
      application (to evaluate lifestyle, family history, individual characteristics),
      anthropometric (height, weight, waist circumference) and biochemical parameters (glucose,
      lipid profile, transaminases, urea, creatinine) measurements. According to inclusion
      criteria, 18 volunteers were able to study participation, but just 16 people remained until
      the end of the study.

      Each treatment was composed by 7 capsules (containing 0.05 mg carotenoid or placebo/kg b.w.)
      which should be consumed once a day (preferably in the morning), during 7 days. It was
      conducted a randomized, double blind, placebo-controlled crossover clinical trial, where 16
      participants received 4 proposed treatments (bixin, norbixin, lycopene and placebo) in
      different periods. To plasma, serum and red blood cells (RBC) obtainment, 2 fasting blood
      collections were made, in the beginning (Day 0) and the end (Day 7) of each treatment. These
      samples were used for evaluating the ex vivo oxidation of LDL induced by copper sulphate and
      biochemical and oxidative biomarkers measurements.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Prevention
masking: Double (Participant, Investigator)
masking description: Double blind
measure: Evaluation of LDL lipid moiety susceptibility to copper induced oxidation - oxidation rate
time frame: Day 0 and Day 7
description: Change (Day 7 - Day 0) of oxidation rate of conjugated dienes formed after copper sulphate addition to LDL particles
measure: Evaluation of LDL protein moiety susceptibility to copper induced oxidation
time frame: Day 0 and Day 7
description: Evaluate the change (Day 7 - Day 0) of loss of tryptophan fluorescence after oxidation induced by copper
measure: Evaluation of LDL lipid moiety susceptibility to copper induced oxidation - lag phase
time frame: Day 0 and Day 7
description: Change (Day 7 - Day 0) of lag phase time of conjugated dienes formed after copper sulphate addition to LDL particles
measure: Evaluation of protein oxidation
time frame: Day 0 and Day 7
description: Change at advanced oxidation protein products levels in plasma
measure: Evaluation of lipid oxidation
time frame: Day 0 and Day 7
description: Change at malondialdehyde levels in plasma and red blood cells
measure: Evaluation of nitric oxide metabolites
time frame: Day 0 and Day 7
description: Change at nitric oxide metabolites levels in serum
measure: Evaluation of plasma antioxidant capacity
time frame: Day 0 and Day 7
description: Change at oxygen radical absorbance capacity in plasma
measure: Evaluation of enzymatic antioxidant defences
time frame: Day 0 and Day 7
description: Change at antioxidant enzymes activities in red blood cells
measure: Evaluation of gluthatione cycle
time frame: Day 0 and Day 7
description: Change at reduced glutathione/oxidized glutathione ratio in red blood cells
measure: Evaluation of red blood cell osmotic fragility
time frame: Day 7
description: Change of red blood cell osmotic fragility after ex vivo exposure to membrane damage inducers
measure: Evaluation of carotenoids levels
time frame: Day 0 and Day 7
description: Change at carotenoids levels in plasma and red blood cells
arm group label: Bixin
arm group type: Experimental
description: Consumption of 0.05 mg bixin/kg b.w. through capsules (once a day) by 7 days in the morning.
arm group label: Norbixin
arm group type: Experimental
description: Consumption of 0.05 mg norbixin/kg b.w. through capsules (once a day) by 7 days in the morning.
arm group label: Lycopene
arm group type: Active Comparator
description: Consumption of 0.05 mg lycopene/kg b.w. through capsules (once a day) by 7 days in the morning.
arm group label: Placebo
arm group type: Placebo Comparator
description: Consumption of 0.05 mg placebo/kg b.w. through capsules (once a day) by 7 days in the morning.
intervention type: Dietary Supplement
intervention name: Bixin
description: Volunteers consumed bixin capsules during 1 week , maintaining their usal lifestyle (avoiding excessive/unusual of fat and carotenoid-containing food, alcohol)
arm group label: Bixin
intervention type: Dietary Supplement
intervention name: Norbixin
description: Volunteers consumed norbixin capsules during 1 week , maintaining their usal lifestyle (avoiding excessive/unusual of fat and carotenoid-containing food, alcohol)
arm group label: Norbixin
intervention type: Dietary Supplement
intervention name: Lycopene
description: Volunteers consumed lycopene capsules during 1 week , maintaining their usal lifestyle (avoiding excessive/unusual of fat and carotenoid-containing food, alcohol)
arm group label: Lycopene
intervention type: Dietary Supplement
intervention name: Placebo
description: Volunteers consumed placebo capsules during 1 week , maintaining their usal lifestyle (avoiding excessive/unusual of fat and carotenoid-containing food, alcohol)
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 35 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Tatiana Emanuelli, Doctor
role: Study Director
affiliation: Universidade Federal de Santa Maria
facility: 
country: Brazil
responsible party type: Principal Investigator
investigator affiliation: Universidade Federal de Santa Maria
investigator full name: Lisiane Conte
investigator title: Master's degree student
mesh term: Atherosclerosis
mesh term: Lycopene
sharing ipd: Undecided
ipd description: Data may be shared after article publication.