<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/NCT03032861</url>
  </required_header>
  <id_info>
    <org_study_id>SaoPSU2</org_study_id>
    <nct_id>NCT03032861</nct_id>
  </id_info>
  <brief_title>The Prebiotic Effect of Daily Intake of Orange Juice Affects the Bioavailability of Flavanones?</brief_title>
  <official_title>Influence of the Prebiotic Effect of Orange Juice on the Bioavailability of Flavanones After Chronic Intake of Orange Juice.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>São Paulo State University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>São Paulo State University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study aimed investigate the chronic effect of orange juice consumption on gut microbiota&#xD;
      and in the bioavailability of flavanones and metabolites by feces, blood and urine analysis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Non-randomized study with interrupted time series and open-label, in which women were&#xD;
      enrolled and advised to not consumed foods containing prebiotic, probiotic and fibers, and&#xD;
      citrus fruits and beverages during 30 days before of intervention (n=10; BMI 23.8 kg/m2; 28&#xD;
      years). After 30 days, the participants will consume during 60 days 300 mL of orange juice&#xD;
      daily. After 60 days of orange juice intervention, the participants will be submitted to 30&#xD;
      days of washout. Samples of blood, urine and feces will collect in five different occasions&#xD;
      (baseline, 30 day, 60 day, 90 day, and 120 day) in order to evaluate the prebiotic effect of&#xD;
      orange juice on gut microbiota and in the bioavailability of its flavanones. The recruitment&#xD;
      process began in September 2016 and the intervention was carried out from October 2016 to&#xD;
      February 2017, and the data analysis will start in February 2017. The sample number took into&#xD;
      account variances on blood hesperitin levels with a type I error α = 0.05 and a type II error&#xD;
      β = 0.2 (80% power) (Silveira et al., 2015). The minimum sample size should have six&#xD;
      individuals into the same group. Considering an approximately 15% dropout rate, the final&#xD;
      sample size of study was constituted by 10 women. Primary endpoint is the changes in total&#xD;
      bacteria population (Lactobacillus spp., Bifidobacterium spp., and reduction of Clostridium&#xD;
      spp.) that can result in increased of butyric, acetic, and propionic acid concentrations, and&#xD;
      reduction of ammonium production. Secondary endpoint is enhancement of bioavailability of&#xD;
      flavanones (hesperitin, naringenin) and metabolites in the blood, urine and feces. Kolmogorov&#xD;
      Smirnov and Levene test will be used to assess the normality and homogeneity of data,&#xD;
      respectively. One-way analysis of variance (ANOVA) will be apply to determine the&#xD;
      intervention effect over the time 0, 30 day, 60 day, 90 day, and 120 day). P significance was&#xD;
      set up ≤ 0.05.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 2016</start_date>
  <completion_date type="Actual">February 2017</completion_date>
  <primary_completion_date type="Actual">October 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Total counting of aerobic bacteria and facultative anaerobic bacteria</measure>
    <time_frame>4 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Determination of butyric acid</measure>
    <time_frame>4 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Determination of acetic acid</measure>
    <time_frame>4 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Ammonium concentration</measure>
    <time_frame>4 mounths</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Bioavailability of hesperitin and naringenin in the blood, urine and feces</measure>
    <time_frame>4 months</time_frame>
    <description>Quantification of hesperidin and naringenin and identification and quantification of their metabolites in the blood, urine and feces</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body mass index</measure>
    <time_frame>4 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body lean mass</measure>
    <time_frame>4 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body fat mass</measure>
    <time_frame>4 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>% body fat</measure>
    <time_frame>4 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ratio waist/hip</measure>
    <time_frame>4 mounths</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glucose</measure>
    <time_frame>4 mounths</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Insulin</measure>
    <time_frame>4 mounths</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total cholesterol</measure>
    <time_frame>4 mounths</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Low density lipoprotein cholesterol</measure>
    <time_frame>4 mounths</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>High density lipoprotein cholesterol</measure>
    <time_frame>4 mounths</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Triglycerides</measure>
    <time_frame>4 mounths</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>hsCRP</measure>
    <time_frame>4 mounths</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alkaline phosphatase</measure>
    <time_frame>4 mounths</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Aspartate enzyme aminotransferase</measure>
    <time_frame>4 mounths</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alanine enzyme aminotransferase</measure>
    <time_frame>4 mounths</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>GammaGT</measure>
    <time_frame>4 mounths</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glycemic curve</measure>
    <time_frame>4 mounths</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Insulin curve</measure>
    <time_frame>4 mounths</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Intestinal Diseases</condition>
  <arm_group>
    <arm_group_label>Orange juice</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ten women will consume 100% orange juice (300 mL/day) during 60 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Orange juice</intervention_name>
    <description>Thirty days before the beginning of trial, women (n= 10; BMI 23.8 kg/m2; 28 years) will be advised to not consumed foods containing prebiotic, probiotic and fibers, and citrus fruits and beverages. After 30 days, the participants will consume 300 mL of orange juice daily during 60 days. After 60 days of orange juice intervention, the participants will be submitted to 30 days of washout. Samples of blood, urine and feces will collect in five different occasions (baseline, 30 day, 60 day, 90 day, and 120 day) in order to evaluate the prebiotic effect of orange juice on gut microbiota and the bioavailability of its flavanones in blood, urine and feces.</description>
    <arm_group_label>Orange juice</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Healthy women BMI 18.5 - 29.9 kg/m2.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Gastrointestinal diseases Pregnant women Regular use of medications Dietary restrictions,&#xD;
        vegetarian diet, macrobiotic, etc. Use of vitamins or dietary supplements Use of probiotics&#xD;
        or prebiotics in the last 3 months and antibiotics in the last 6 months.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Thais B Cesar, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sao Paulo State University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sao Paulo State University &quot;Julio de Mesquita Filho&quot;, Faculdade de Ciências Farmacêuticas</name>
      <address>
        <city>Araraquara</city>
        <state>Sao Paulo</state>
        <zip>14800-903</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <results_reference>
    <citation>Silveira JQ, Cesar TB, Manthey JA, Baldwin EA, Bai J, Raithore S. Pharmacokinetics of flavanone glycosides after ingestion of single doses of fresh-squeezed orange juice versus commercially processed orange juice in healthy humans. J Agric Food Chem. 2014 Dec 31;62(52):12576-84. doi: 10.1021/jf5038163. Epub 2014 Dec 15.</citation>
    <PMID>25495754</PMID>
  </results_reference>
  <results_reference>
    <citation>Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser. 2000;894:i-xii, 1-253.</citation>
    <PMID>11234459</PMID>
  </results_reference>
  <results_reference>
    <citation>Kanaze FI, Bounartzi MI, Georgarakis M, Niopas I. Pharmacokinetics of the citrus flavanone aglycones hesperetin and naringenin after single oral administration in human subjects. Eur J Clin Nutr. 2007 Apr;61(4):472-7. doi: 10.1038/sj.ejcn.1602543. Epub 2006 Oct 18.</citation>
    <PMID>17047689</PMID>
  </results_reference>
  <verification_date>April 2017</verification_date>
  <study_first_submitted>January 6, 2017</study_first_submitted>
  <study_first_submitted_qc>January 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <last_update_submitted>April 25, 2017</last_update_submitted>
  <last_update_submitted_qc>April 25, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">April 26, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>São Paulo State University</investigator_affiliation>
    <investigator_full_name>Thais Cesar</investigator_full_name>
    <investigator_title>PhD</investigator_title>
  </responsible_party>
  <keyword>Orange juice</keyword>
  <keyword>Microbiota</keyword>
  <keyword>Prebiotic</keyword>
  <keyword>Flavanones</keyword>
  <keyword>Bioavailability</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Intestinal Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>There is still no decision regarding if the individual participant data (IPD) will be available to other researchers.</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/NCT03032861
org study id: SaoPSU2
nct id: NCT03032861
lead sponsor: 
has dmc: Yes
This study aimed investigate the chronic effect of orange juice consumption on gut microbiota
      and in the bioavailability of flavanones and metabolites by feces, blood and urine analysis.
Non-randomized study with interrupted time series and open-label, in which women were
      enrolled and advised to not consumed foods containing prebiotic, probiotic and fibers, and
      citrus fruits and beverages during 30 days before of intervention (n=10; BMI 23.8 kg/m2; 28
      years). After 30 days, the participants will consume during 60 days 300 mL of orange juice
      daily. After 60 days of orange juice intervention, the participants will be submitted to 30
      days of washout. Samples of blood, urine and feces will collect in five different occasions
      (baseline, 30 day, 60 day, 90 day, and 120 day) in order to evaluate the prebiotic effect of
      orange juice on gut microbiota and in the bioavailability of its flavanones. The recruitment
      process began in September 2016 and the intervention was carried out from October 2016 to
      February 2017, and the data analysis will start in February 2017. The sample number took into
      account variances on blood hesperitin levels with a type I error α = 0.05 and a type II error
      β = 0.2 (80% power) (Silveira et al., 2015). The minimum sample size should have six
      individuals into the same group. Considering an approximately 15% dropout rate, the final
      sample size of study was constituted by 10 women. Primary endpoint is the changes in total
      bacteria population (Lactobacillus spp., Bifidobacterium spp., and reduction of Clostridium
      spp.) that can result in increased of butyric, acetic, and propionic acid concentrations, and
      reduction of ammonium production. Secondary endpoint is enhancement of bioavailability of
      flavanones (hesperitin, naringenin) and metabolites in the blood, urine and feces. Kolmogorov
      Smirnov and Levene test will be used to assess the normality and homogeneity of data,
      respectively. One-way analysis of variance (ANOVA) will be apply to determine the
      intervention effect over the time 0, 30 day, 60 day, 90 day, and 120 day). P significance was
      set up ≤ 0.05.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Total counting of aerobic bacteria and facultative anaerobic bacteria
time frame: 4 months
measure: Determination of butyric acid
time frame: 4 months
measure: Determination of acetic acid
time frame: 4 months
measure: Ammonium concentration
time frame: 4 mounths
measure: Bioavailability of hesperitin and naringenin in the blood, urine and feces
time frame: 4 months
description: Quantification of hesperidin and naringenin and identification and quantification of their metabolites in the blood, urine and feces
measure: Body mass index
time frame: 4 months
measure: Body lean mass
time frame: 4 months
measure: Body fat mass
time frame: 4 months
measure: % body fat
time frame: 4 months
measure: Ratio waist/hip
time frame: 4 mounths
measure: Glucose
time frame: 4 mounths
measure: Insulin
time frame: 4 mounths
measure: Total cholesterol
time frame: 4 mounths
measure: Low density lipoprotein cholesterol
time frame: 4 mounths
measure: High density lipoprotein cholesterol
time frame: 4 mounths
measure: Triglycerides
time frame: 4 mounths
measure: hsCRP
time frame: 4 mounths
measure: Alkaline phosphatase
time frame: 4 mounths
measure: Aspartate enzyme aminotransferase
time frame: 4 mounths
measure: Alanine enzyme aminotransferase
time frame: 4 mounths
measure: GammaGT
time frame: 4 mounths
measure: Glycemic curve
time frame: 4 mounths
measure: Insulin curve
time frame: 4 mounths
arm group label: Orange juice
arm group type: Experimental
description: Ten women will consume 100% orange juice (300 mL/day) during 60 days.
intervention type: Other
intervention name: Orange juice
description: Thirty days before the beginning of trial, women (n= 10; BMI 23.8 kg/m2; 28 years) will be advised to not consumed foods containing prebiotic, probiotic and fibers, and citrus fruits and beverages. After 30 days, the participants will consume 300 mL of orange juice daily during 60 days. After 60 days of orange juice intervention, the participants will be submitted to 30 days of washout. Samples of blood, urine and feces will collect in five different occasions (baseline, 30 day, 60 day, 90 day, and 120 day) in order to evaluate the prebiotic effect of orange juice on gut microbiota and the bioavailability of its flavanones in blood, urine and feces.
arm group label: Orange juice
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Thais B Cesar, PhD
role: Principal Investigator
affiliation: Sao Paulo State University
facility: 
country: Brazil
citation: Silveira JQ, Cesar TB, Manthey JA, Baldwin EA, Bai J, Raithore S. Pharmacokinetics of flavanone glycosides after ingestion of single doses of fresh-squeezed orange juice versus commercially processed orange juice in healthy humans. J Agric Food Chem. 2014 Dec 31;62(52):12576-84. doi: 10.1021/jf5038163. Epub 2014 Dec 15.
PMID: 25495754
citation: Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser. 2000;894:i-xii, 1-253.
PMID: 11234459
citation: Kanaze FI, Bounartzi MI, Georgarakis M, Niopas I. Pharmacokinetics of the citrus flavanone aglycones hesperetin and naringenin after single oral administration in human subjects. Eur J Clin Nutr. 2007 Apr;61(4):472-7. doi: 10.1038/sj.ejcn.1602543. Epub 2006 Oct 18.
PMID: 17047689
responsible party type: Principal Investigator
investigator affiliation: São Paulo State University
investigator full name: Thais Cesar
investigator title: PhD
mesh term: Intestinal Diseases
sharing ipd: Undecided
ipd description: There is still no decision regarding if the individual participant data (IPD) will be available to other researchers.