<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/NCT04411758</url>
  </required_header>
  <id_info>
    <org_study_id>Denise Mafra8</org_study_id>
    <nct_id>NCT04411758</nct_id>
  </id_info>
  <brief_title>Propolis for Patients With Chronic Kidney Disease.</brief_title>
  <official_title>Propolis as a New Strategy in Modulating Inflammation in Patients With Chronic Kidney Disease.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universidade Federal Fluminense</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Universidade Federal Fluminense</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>
      To evaluate the effects of propolis extract on inflammation in participants with chronic&#xD;
      kidney disease.&#xD;
&#xD;
      Specific objectives&#xD;
&#xD;
      To assess before and after the intervention period:&#xD;
&#xD;
        -  The expression of transcription factors (nuclear factor-kB), antioxidant enzymes&#xD;
           (heme-oxygenase-1), inflammasome receptor, peroxisome proliferator-activated receptor-γ,&#xD;
           as well as the levels of inflammatory cytokines (IL-6, Tumor nuclear factor-α,&#xD;
           C-reactive protein, interleukin 1) and E-selectin adhesion molecules;&#xD;
&#xD;
        -  The levels of protein expression of inflammatory markers and antioxidant enzymes;&#xD;
&#xD;
        -  The profile of the intestinal microbiota of stool samples from the research&#xD;
           participants;&#xD;
&#xD;
        -  Plasma levels of substances reactive to thiobarbituric acid and oxidized low density&#xD;
           lipoprotein as a marker of oxidative stress;&#xD;
&#xD;
        -  Routine and anthropometric laboratory variables, indicative of the metabolic profile of&#xD;
           the research participants;&#xD;
&#xD;
        -  Assess blood pressure, 6-minute walk test, recovery heart rate and chair lift test to&#xD;
           assess the functional capacity of the research participants;&#xD;
&#xD;
        -  Assess atherogenic risk;&#xD;
&#xD;
        -  Food intake and nutritional status; Compare data between the intervention and control&#xD;
           groups.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Chronic kidney disease (CKD) has chronic systemic inflammation as an important component of&#xD;
      multifactorial origin, a factor related to both the progression and outcomes of CKD, being&#xD;
      involved in all causes of mortality in these patients, such as cardiovascular disease. In&#xD;
      this context, some nutritional strategies have been proposed as an adjuvant therapeutic&#xD;
      alternative to modulate inflammation, starting from the consolidated knowledge of the role of&#xD;
      nutrients and bioactive compounds on the expression of genes related to inflammation and&#xD;
      oxidative stress, factors that feed on each other. In view of this scenario, propolis, a&#xD;
      substance made up of a combination of several chemical components with broad potential&#xD;
      biological activity, appears as a promising alternative to modulate inflammation in patients&#xD;
      with CKD. However, clinical evidence to assess the effects of propolis in patients with CKD&#xD;
      is scarce, and there are no studies that have investigated its effects on gene expression and&#xD;
      markers related to inflammation in these patients. Thus, the present project proposes a&#xD;
      longitudinal study of the clinical trial type that aims to evaluate the effects of propolis&#xD;
      alcoholic extract on transcription factors and inflammatory markers in patients with CKD.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 12, 2021</start_date>
  <completion_date type="Anticipated">June 20, 2023</completion_date>
  <primary_completion_date type="Anticipated">May 29, 2023</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>
    <intervention_model_description>In this clinical trial, participants with CKD undergoing hemodialysis or peritoneal dialysis will be instructed to use 4 capsules of 500mg/day containing concentrated and standardized dry EPP-AF® green propolis extract for 2 months or placebo (4 capsules of 500mg/day of magnesium stearate, silicon dioxide and microcrystalline cellulose) for two months, and then the groups will be crossed and will receive the same amount of propolis as the first group.</intervention_model_description>
    <primary_purpose>Health Services Research</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in cytokines plasma levels measured by ELISA after supplementation with propolis.</measure>
    <time_frame>4 months</time_frame>
    <description>IL-6, Tumor necrosis factor (TNF)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change the expression of transcription factors (nuclear factor-kB), antioxidant enzymes (heme-oxygenase-1), inflammasome, peroxisome proliferator-activated receptor-γ</measure>
    <time_frame>4 months</time_frame>
    <description>nuclear factor (NF)-kappa B</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change the profile of the intestinal microbiota of stool samples</measure>
    <time_frame>4 months</time_frame>
    <description>uremic toxins</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Chronic Kidney Diseases</condition>
  <condition>Inflammation</condition>
  <arm_group>
    <arm_group_label>Placebo Group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>4 capsules of 500mg/day of magnesium stearate, silicon dioxide and microcrystalline cellulose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Propolis Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 capsules of 500mg/day containing concentrated and standardized dry EPP-AF® green propolis extract for 2 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Propolis</intervention_name>
    <description>4 capsules of 500mg/day containing concentrated and standardized dry EPP-AF® green propolis extract for 2 months and after washout, more two months crossover</description>
    <arm_group_label>Placebo Group</arm_group_label>
    <arm_group_label>Propolis Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        • Aged 18 years or older&#xD;
&#xD;
        - with fistula arteriovenous&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients pregnant&#xD;
&#xD;
          -  Smokers&#xD;
&#xD;
          -  Using antibiotics in the last three months&#xD;
&#xD;
          -  Using antioxidant supplements as antioxidant vitamins, probiotic, prebiotic, symbiotic&#xD;
             and antibiotics in the last three months&#xD;
&#xD;
          -  Clinical diagnosis of infectious diseases&#xD;
&#xD;
          -  Clinical diagnosis of Cancer&#xD;
&#xD;
          -  Clinical diagnosis of AIDS - for PD patients - no peritonitis&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Denise Mafra, phd</last_name>
    <role>Principal Investigator</role>
    <affiliation>Universidade Federal Fluminense</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Denise Mafra, PhD</last_name>
    <phone>5521985683003</phone>
    <email>dmafra30@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Denise Mafra</name>
      <address>
        <city>Niterói</city>
        <state>Rio De Janeiro</state>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Denise Mafra</last_name>
      <phone>+55 21 985683003</phone>
      <email>dmafra30@gmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>May 28, 2020</study_first_submitted>
  <study_first_submitted_qc>May 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <last_update_submitted>September 15, 2022</last_update_submitted>
  <last_update_submitted_qc>September 15, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 19, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>chronic kidney disease</keyword>
  <keyword>non-dialysis</keyword>
  <keyword>propolis</keyword>
  <keyword>inflammation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Renal Insufficiency, Chronic</mesh_term>
    <mesh_term>Inflammation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Propolis</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT04411758
org study id: Denise Mafra8
nct id: NCT04411758
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
To evaluate the effects of propolis extract on inflammation in participants with chronic
      kidney disease.

      Specific objectives

      To assess before and after the intervention period:

        -  The expression of transcription factors (nuclear factor-kB), antioxidant enzymes
           (heme-oxygenase-1), inflammasome receptor, peroxisome proliferator-activated receptor-γ,
           as well as the levels of inflammatory cytokines (IL-6, Tumor nuclear factor-α,
           C-reactive protein, interleukin 1) and E-selectin adhesion molecules;

        -  The levels of protein expression of inflammatory markers and antioxidant enzymes;

        -  The profile of the intestinal microbiota of stool samples from the research
           participants;

        -  Plasma levels of substances reactive to thiobarbituric acid and oxidized low density
           lipoprotein as a marker of oxidative stress;

        -  Routine and anthropometric laboratory variables, indicative of the metabolic profile of
           the research participants;

        -  Assess blood pressure, 6-minute walk test, recovery heart rate and chair lift test to
           assess the functional capacity of the research participants;

        -  Assess atherogenic risk;

        -  Food intake and nutritional status; Compare data between the intervention and control
           groups.
Chronic kidney disease (CKD) has chronic systemic inflammation as an important component of
      multifactorial origin, a factor related to both the progression and outcomes of CKD, being
      involved in all causes of mortality in these patients, such as cardiovascular disease. In
      this context, some nutritional strategies have been proposed as an adjuvant therapeutic
      alternative to modulate inflammation, starting from the consolidated knowledge of the role of
      nutrients and bioactive compounds on the expression of genes related to inflammation and
      oxidative stress, factors that feed on each other. In view of this scenario, propolis, a
      substance made up of a combination of several chemical components with broad potential
      biological activity, appears as a promising alternative to modulate inflammation in patients
      with CKD. However, clinical evidence to assess the effects of propolis in patients with CKD
      is scarce, and there are no studies that have investigated its effects on gene expression and
      markers related to inflammation in these patients. Thus, the present project proposes a
      longitudinal study of the clinical trial type that aims to evaluate the effects of propolis
      alcoholic extract on transcription factors and inflammatory markers in patients with CKD.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: In this clinical trial, participants with CKD undergoing hemodialysis or peritoneal dialysis will be instructed to use 4 capsules of 500mg/day containing concentrated and standardized dry EPP-AF® green propolis extract for 2 months or placebo (4 capsules of 500mg/day of magnesium stearate, silicon dioxide and microcrystalline cellulose) for two months, and then the groups will be crossed and will receive the same amount of propolis as the first group.
primary purpose: Health Services Research
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Change in cytokines plasma levels measured by ELISA after supplementation with propolis.
time frame: 4 months
description: IL-6, Tumor necrosis factor (TNF)
measure: Change the expression of transcription factors (nuclear factor-kB), antioxidant enzymes (heme-oxygenase-1), inflammasome, peroxisome proliferator-activated receptor-γ
time frame: 4 months
description: nuclear factor (NF)-kappa B
measure: Change the profile of the intestinal microbiota of stool samples
time frame: 4 months
description: uremic toxins
arm group label: Placebo Group
arm group type: Placebo Comparator
description: 4 capsules of 500mg/day of magnesium stearate, silicon dioxide and microcrystalline cellulose
arm group label: Propolis Group
arm group type: Experimental
description: 4 capsules of 500mg/day containing concentrated and standardized dry EPP-AF® green propolis extract for 2 months
intervention type: Dietary Supplement
intervention name: Propolis
description: 4 capsules of 500mg/day containing concentrated and standardized dry EPP-AF® green propolis extract for 2 months and after washout, more two months crossover
arm group label: Placebo Group
arm group label: Propolis Group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Denise Mafra, phd
role: Principal Investigator
affiliation: Universidade Federal Fluminense
last name: Denise Mafra, PhD
phone: 5521985683003
email: dmafra30@gmail.com
facility: 
status: Recruiting
contact: 
country: Brazil
responsible party type: Sponsor
mesh term: Kidney Diseases
mesh term: Renal Insufficiency, Chronic
mesh term: Inflammation
mesh term: Propolis
sharing ipd: No