<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/NCT04437147</url>
  </required_header>
  <id_info>
    <org_study_id>Fabiana Rosa</org_study_id>
    <nct_id>NCT04437147</nct_id>
  </id_info>
  <brief_title>Effect of Probiotics on Functional Constipation in Adults</brief_title>
  <acronym>PROBCON</acronym>
  <official_title>The Effect of Probiotics on Functional Constipation in Adults: Double-blind, Randomized, Placebo-controlled Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Luciane Cruz Lopes</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Sorocaba</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Introduction:&#xD;
&#xD;
      Functional constipation is a symptom-based gastrointestinal disorder without an organic&#xD;
      origin (eg, bowel obstruction). It has a prevalence of 14% in adults.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      The objective of trial is to evaluate the efficacy and safety of two different probiotic&#xD;
      blends in adults subjects with functional constipation.&#xD;
&#xD;
      Methods:&#xD;
&#xD;
      A double-blind, randomized, placebo-controlled study will be conducted for up to two years to&#xD;
      evaluate the efficacy of two different probiotic mixtures: (Mixture 1) Lactobacillus&#xD;
      acidophilus, Bifidobacterium bifidum and Lactobacillus rhamnosus (3 billion CFU); (Mixture 2)&#xD;
      Lactobacillus acidophilus, Bifidobacterium bifidum, Lactobacillus rhamnosus, Lactobacillus&#xD;
      paracasei, Bifidobacterium longum, Bifidobacterium lactis, Lactobacillus defensis,&#xD;
      Bifidobacterium animallis (8 billion CFU).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study involve 150 healthy volunteers with functional constipation.The sample size was&#xD;
      based on literature reviews of the probiotics' effect comparing the differences between&#xD;
      means.&#xD;
&#xD;
      After confirmation of eligibility and obtaining written informed consent, the patients will&#xD;
      be randomized (stratification for blocks) to recivied the interventions. The patients and the&#xD;
      phisician will be blinded to the treatment received. The eligible patients will be allocated&#xD;
      (1:1:1) to treatment with either the probiotics supplements or placebo. Subjects will be&#xD;
      instructed to ingest one sachet before breakfast, by mixing the powder in water and drinking&#xD;
      it. The sachets will be stored at room temperature.&#xD;
&#xD;
      Data handling and record keeping Case report forms will be used to record data for all&#xD;
      participants, and will be completed by the research doctor, who will also enter the data into&#xD;
      an electronic database.&#xD;
&#xD;
      Study schedule and location After inclusion, all further treatments will be managed at the&#xD;
      primary care center where the subject was recruited. A research doctor and a research&#xD;
      pharmacist will be responsible for all contacts with patients.&#xD;
&#xD;
      Local of study development Recruitment of patients to this study will be made by&#xD;
      collaboration with the Gastroenterolgy Clinic at Avenue Dr Armando Sales de Oliveira 371,&#xD;
      Trujilo, Sorocaba, State of São Paulo, Brazil from March 2020 to April 2020. Sorocaba is a&#xD;
      Brazilian municipality in the interior of the state of São Paulo. It is the fourth most&#xD;
      populous in the interior of São Paulo in the Southeast of the country, and the most populous&#xD;
      in the southern region of São Paulo, with a population of 671,186 inhabitants, estimated by&#xD;
      IBGE for July 1, 2018.&#xD;
&#xD;
      For comparison of three groups, an independent t-test will be applied for continuous&#xD;
      variables and Mann-Whitney for non-continuous variables. Analysis of adverse events (if any)&#xD;
      will be performed using Chi-Square test and Fisher's exact test following assumptions of&#xD;
      randomness, independence and size. Significance differences will be set at p&lt;0.05.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 11, 2020</start_date>
  <completion_date type="Actual">January 28, 2021</completion_date>
  <primary_completion_date type="Actual">November 30, 2020</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>Interventions: in particular, subjects were divided into 3 groups: i) 50 subjects in the group A will receive placebo, ii) 50 subjetcs in the group B will receive mixed L. acidophilus LA 02 ID 1688, B. bifidum BB 01 ID 1722 and L. rhamnosus LR 04 ID 1132 (1 x 10⁹ colony-forming units/d of each strain) and 50 subjects em the group C will receive L. acidophilus LA 02 ID 1688, B. bifidum BB 01 ID 1722, L. rhamnosus LR 04 ID 1132, L. paracasei LPC 00 ID 1076, B. longum BL 03 ID 1152, B. lactis BS 01 ID 1195, L. casei LC 03 ID 1872, B. animalis LMG 10508 (1 x 10⁹ colony-forming units/d of each strain) for 30 days. At the beginning of the interventional study, the healthy status of volunteers will be evaluated by a complete, laboratory and by the clinical evaluation by the doctor using as reference ROMA IV for intestinal constipation. Exclusion criteria will be items of gastrointestinal diseases, pregnant and antibiotic intake.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
    <masking_description>The phisician (care provider), the research subjects (participants) and outcome assessor (had access to the results) will be blinded. All groups received sachets with the same characteristics (taste and packaging) different only in the numbering of the manufacturing batches. The phisician separated each volunteer in according to lot number corresponding to the randomisation.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Changed in the number of Bowel movements. Changed for more than 3 per week was considered a clinical response.</measure>
    <time_frame>30 days</time_frame>
    <description>Changed number of bowel movements evaluated weekly</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in the Bristol stool form scale at 4 weeks after Probiotics. Recovery to types 3-4 was considered a clinical response.</measure>
    <time_frame>30 days</time_frame>
    <description>The Bristol scale ranges from 1-7, with 1-2 being constipated, 3-5 normal and 6-7 diarrhea.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Subject withdrawal</measure>
    <time_frame>30 days</time_frame>
    <description>The volunteers can withdraw from the study at any time by their own request, or can be withdrawn at any time at the discretion of the investigator for safety. Volunteers will also be withdrawn from the study in the event of treatment interruption for any reason, whether due to forgetfulness or to experiencing undue intestinal discomfort</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>30 days</time_frame>
    <description>Adverse events are undesirable signs or symptoms that occur during the study and whose cause may or may not be causal related to the treatment. All adverse events considered possibly, probably or related to the test product will be noted down on the patient's form.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serious adverse events</measure>
    <time_frame>30 days</time_frame>
    <description>Serious adverse events are defined as events that are fatal, life-threatening, disabling or result in hospitalization or prolonged stay, or result in malformation, whether related to the test product or otherwise.&#xD;
According to previous studies, probiotics are safe and any serious adverse event that could possibly, probably or be related to the test products will be considered unexpected. All unexpected serious adverse events will be reported to the physician. Any serious adverse event that may be related to the test product will immediately lead to discontinuation of the test product</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">150</enrollment>
  <condition>Functional Constipation</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>a) Control placebo (P1) Component Vitamin C (Ascorbic acid) 45 mg,Vitamin B1 (Thiamine) 1.1 mg, Vitamin B2 (Riboflavin) 1.1 mg,Vitamin D-3 40,000,000 IU / GR (Cholecalciferol) 34 mcg, Magnesium hydroxide 0.3 g, Calcium Carbonate 0.5 g, Natural Vanilla Flavor Powder 0.03 g,Fos (Fructooligosaccharides) qsp 3 g, for 30 days, once a day by sachet</description>
  </arm_group>
  <arm_group>
    <arm_group_label>3 Billion CFU strains of probiotics</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>b) 3 Billion CFU (P2) Component Lactobacillus acidophilus LA 02 ID 1688 1 billion CFU,Bifidobacterium bifidum BB 01 ID 1722 1 billion CFU, Lactobacillus rhamnosus LR 04 ID 1132 1 billion CFU,Vitamin C (Ascorbic acid) 45 mg,Vitamin B1 (Thiamine) 1.1 mg, Vitamin B2 (Riboflavin) 1.1 mg,Vitamin D-3 40,000,000 IU / GR (Cholecalciferol) 34 mcg, Magnesium hydroxide 0.3 g, Calcium Carbonate 0.5 g, Natural Vanilla Flavor Powder 0.03 g,Fos (Fructooligosaccharides) qsp 3 g, for 30 days, once a day by sachet</description>
  </arm_group>
  <arm_group>
    <arm_group_label>8 Billion CFU strains of probiotics</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>c) 8 Billion UFC (P3) Component Lactobacillus paracasei LPC 00 ID 1076 1 billion CFU;Bifidobacterium longum BL 03 ID 1152 1 billion CFU; Bifidobacterium lactis BS 01 ID 1195 1 billion CFU;Lactobacillus casei LC 03 ID 1872 1 billion CFU; Bifidobacterium animalis LMG 10508 1 billion CFU; Lactobacillus acidophilus LA 02 ID 1688 1 billion CFU,Bifidobacterium bifidum BB 01 ID 1722 1 billion CFU, Lactobacillus rhamnosus LR 04 ID 1132 1 billion CFU,Vitamin C (Ascorbic acid) 45 mg,Vitamin B1 (Thiamine) 1.1 mg, Vitamin B2 (Riboflavin) 1.1 mg,Vitamin D-3 40,000,000 IU / GR (Cholecalciferol) 34 mcg, Magnesium hydroxide 0.3 g, Calcium Carbonate 0.5 g, Natural Vanilla Flavor Powder 0.03 g,Fos (Fructooligosaccharides) qsp 3 g, for 30 days, once a day by sachet</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Fibers with vitamins and minerals will be administered for 30 days once a day in sachets</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Group Placebo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>3 Billion UFC strains of probiotics</intervention_name>
    <description>Fibers with vitamins and minerals will be administered for 30 days once a day in sachets with 3 billion CFU strains of probiotics</description>
    <arm_group_label>3 Billion CFU strains of probiotics</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>8 Billion UFC strains of probiotics</intervention_name>
    <description>Fibers with vitamins and minerals will be administered for 30 days once a day in sachets with 8 billion CFU strains of probiotics</description>
    <arm_group_label>8 Billion CFU strains of probiotics</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        -Clinical diagnosis of functional constipation according to Rome IV. Granting of written&#xD;
        informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Presence of gastrointestinal diseases&#xD;
&#xD;
          -  Ingestion of antibiotics or dietary supplements containing probiotics or prebiotics in&#xD;
             the last 15 days&#xD;
&#xD;
          -  Pregnancy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Fabiana R MITELMAO, master</last_name>
    <role>Principal Investigator</role>
    <affiliation>UNIVERSIDADE DE SOROCABA</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Universidade de Sorocaba</name>
      <address>
        <city>Sorocaba</city>
        <state>SP</state>
        <zip>19023000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>June 3, 2020</study_first_submitted>
  <study_first_submitted_qc>June 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 18, 2020</study_first_posted>
  <last_update_submitted>January 28, 2021</last_update_submitted>
  <last_update_submitted_qc>January 28, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 29, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Sorocaba</investigator_affiliation>
    <investigator_full_name>Luciane Cruz Lopes</investigator_full_name>
    <investigator_title>Principal Investigator: Fabiana Cristina Rosa Mitelmão</investigator_title>
  </responsible_party>
  <keyword>Lactobacillus</keyword>
  <keyword>Bifidobacterium</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Constipation</mesh_term>
  </condition_browse>
  <!-- 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/NCT04437147
org study id: Fabiana Rosa
nct id: NCT04437147
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Introduction:

      Functional constipation is a symptom-based gastrointestinal disorder without an organic
      origin (eg, bowel obstruction). It has a prevalence of 14% in adults.

      Objective:

      The objective of trial is to evaluate the efficacy and safety of two different probiotic
      blends in adults subjects with functional constipation.

      Methods:

      A double-blind, randomized, placebo-controlled study will be conducted for up to two years to
      evaluate the efficacy of two different probiotic mixtures: (Mixture 1) Lactobacillus
      acidophilus, Bifidobacterium bifidum and Lactobacillus rhamnosus (3 billion CFU); (Mixture 2)
      Lactobacillus acidophilus, Bifidobacterium bifidum, Lactobacillus rhamnosus, Lactobacillus
      paracasei, Bifidobacterium longum, Bifidobacterium lactis, Lactobacillus defensis,
      Bifidobacterium animallis (8 billion CFU).
The study involve 150 healthy volunteers with functional constipation.The sample size was
      based on literature reviews of the probiotics' effect comparing the differences between
      means.

      After confirmation of eligibility and obtaining written informed consent, the patients will
      be randomized (stratification for blocks) to recivied the interventions. The patients and the
      phisician will be blinded to the treatment received. The eligible patients will be allocated
      (1:1:1) to treatment with either the probiotics supplements or placebo. Subjects will be
      instructed to ingest one sachet before breakfast, by mixing the powder in water and drinking
      it. The sachets will be stored at room temperature.

      Data handling and record keeping Case report forms will be used to record data for all
      participants, and will be completed by the research doctor, who will also enter the data into
      an electronic database.

      Study schedule and location After inclusion, all further treatments will be managed at the
      primary care center where the subject was recruited. A research doctor and a research
      pharmacist will be responsible for all contacts with patients.

      Local of study development Recruitment of patients to this study will be made by
      collaboration with the Gastroenterolgy Clinic at Avenue Dr Armando Sales de Oliveira 371,
      Trujilo, Sorocaba, State of São Paulo, Brazil from March 2020 to April 2020. Sorocaba is a
      Brazilian municipality in the interior of the state of São Paulo. It is the fourth most
      populous in the interior of São Paulo in the Southeast of the country, and the most populous
      in the southern region of São Paulo, with a population of 671,186 inhabitants, estimated by
      IBGE for July 1, 2018.

      For comparison of three groups, an independent t-test will be applied for continuous
      variables and Mann-Whitney for non-continuous variables. Analysis of adverse events (if any)
      will be performed using Chi-Square test and Fisher's exact test following assumptions of
      randomness, independence and size. Significance differences will be set at p<0.05.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Interventions: in particular, subjects were divided into 3 groups: i) 50 subjects in the group A will receive placebo, ii) 50 subjetcs in the group B will receive mixed L. acidophilus LA 02 ID 1688, B. bifidum BB 01 ID 1722 and L. rhamnosus LR 04 ID 1132 (1 x 10⁹ colony-forming units/d of each strain) and 50 subjects em the group C will receive L. acidophilus LA 02 ID 1688, B. bifidum BB 01 ID 1722, L. rhamnosus LR 04 ID 1132, L. paracasei LPC 00 ID 1076, B. longum BL 03 ID 1152, B. lactis BS 01 ID 1195, L. casei LC 03 ID 1872, B. animalis LMG 10508 (1 x 10⁹ colony-forming units/d of each strain) for 30 days. At the beginning of the interventional study, the healthy status of volunteers will be evaluated by a complete, laboratory and by the clinical evaluation by the doctor using as reference ROMA IV for intestinal constipation. Exclusion criteria will be items of gastrointestinal diseases, pregnant and antibiotic intake.
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Outcomes Assessor)
masking description: The phisician (care provider), the research subjects (participants) and outcome assessor (had access to the results) will be blinded. All groups received sachets with the same characteristics (taste and packaging) different only in the numbering of the manufacturing batches. The phisician separated each volunteer in according to lot number corresponding to the randomisation.
measure: Changed in the number of Bowel movements. Changed for more than 3 per week was considered a clinical response.
time frame: 30 days
description: Changed number of bowel movements evaluated weekly
measure: Change in the Bristol stool form scale at 4 weeks after Probiotics. Recovery to types 3-4 was considered a clinical response.
time frame: 30 days
description: The Bristol scale ranges from 1-7, with 1-2 being constipated, 3-5 normal and 6-7 diarrhea.
measure: Subject withdrawal
time frame: 30 days
description: The volunteers can withdraw from the study at any time by their own request, or can be withdrawn at any time at the discretion of the investigator for safety. Volunteers will also be withdrawn from the study in the event of treatment interruption for any reason, whether due to forgetfulness or to experiencing undue intestinal discomfort
measure: Adverse events
time frame: 30 days
description: Adverse events are undesirable signs or symptoms that occur during the study and whose cause may or may not be causal related to the treatment. All adverse events considered possibly, probably or related to the test product will be noted down on the patient's form.
measure: Serious adverse events
time frame: 30 days
description: Serious adverse events are defined as events that are fatal, life-threatening, disabling or result in hospitalization or prolonged stay, or result in malformation, whether related to the test product or otherwise.
According to previous studies, probiotics are safe and any serious adverse event that could possibly, probably or be related to the test products will be considered unexpected. All unexpected serious adverse events will be reported to the physician. Any serious adverse event that may be related to the test product will immediately lead to discontinuation of the test product
arm group label: Placebo
arm group type: Placebo Comparator
description: a) Control placebo (P1) Component Vitamin C (Ascorbic acid) 45 mg,Vitamin B1 (Thiamine) 1.1 mg, Vitamin B2 (Riboflavin) 1.1 mg,Vitamin D-3 40,000,000 IU / GR (Cholecalciferol) 34 mcg, Magnesium hydroxide 0.3 g, Calcium Carbonate 0.5 g, Natural Vanilla Flavor Powder 0.03 g,Fos (Fructooligosaccharides) qsp 3 g, for 30 days, once a day by sachet
arm group label: 3 Billion CFU strains of probiotics
arm group type: Active Comparator
description: b) 3 Billion CFU (P2) Component Lactobacillus acidophilus LA 02 ID 1688 1 billion CFU,Bifidobacterium bifidum BB 01 ID 1722 1 billion CFU, Lactobacillus rhamnosus LR 04 ID 1132 1 billion CFU,Vitamin C (Ascorbic acid) 45 mg,Vitamin B1 (Thiamine) 1.1 mg, Vitamin B2 (Riboflavin) 1.1 mg,Vitamin D-3 40,000,000 IU / GR (Cholecalciferol) 34 mcg, Magnesium hydroxide 0.3 g, Calcium Carbonate 0.5 g, Natural Vanilla Flavor Powder 0.03 g,Fos (Fructooligosaccharides) qsp 3 g, for 30 days, once a day by sachet
arm group label: 8 Billion CFU strains of probiotics
arm group type: Active Comparator
description: c) 8 Billion UFC (P3) Component Lactobacillus paracasei LPC 00 ID 1076 1 billion CFU;Bifidobacterium longum BL 03 ID 1152 1 billion CFU; Bifidobacterium lactis BS 01 ID 1195 1 billion CFU;Lactobacillus casei LC 03 ID 1872 1 billion CFU; Bifidobacterium animalis LMG 10508 1 billion CFU; Lactobacillus acidophilus LA 02 ID 1688 1 billion CFU,Bifidobacterium bifidum BB 01 ID 1722 1 billion CFU, Lactobacillus rhamnosus LR 04 ID 1132 1 billion CFU,Vitamin C (Ascorbic acid) 45 mg,Vitamin B1 (Thiamine) 1.1 mg, Vitamin B2 (Riboflavin) 1.1 mg,Vitamin D-3 40,000,000 IU / GR (Cholecalciferol) 34 mcg, Magnesium hydroxide 0.3 g, Calcium Carbonate 0.5 g, Natural Vanilla Flavor Powder 0.03 g,Fos (Fructooligosaccharides) qsp 3 g, for 30 days, once a day by sachet
intervention type: Dietary Supplement
intervention name: Placebo
description: Fibers with vitamins and minerals will be administered for 30 days once a day in sachets
arm group label: Placebo
other name: Group Placebo
intervention type: Dietary Supplement
intervention name: 3 Billion UFC strains of probiotics
description: Fibers with vitamins and minerals will be administered for 30 days once a day in sachets with 3 billion CFU strains of probiotics
arm group label: 3 Billion CFU strains of probiotics
intervention type: Dietary Supplement
intervention name: 8 Billion UFC strains of probiotics
description: Fibers with vitamins and minerals will be administered for 30 days once a day in sachets with 8 billion CFU strains of probiotics
arm group label: 8 Billion CFU strains of probiotics
criteria: 
gender: All
minimum age: 20 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Fabiana R MITELMAO, master
role: Principal Investigator
affiliation: UNIVERSIDADE DE SOROCABA
facility: 
country: Brazil
responsible party type: Sponsor-Investigator
investigator affiliation: University of Sorocaba
investigator full name: Luciane Cruz Lopes
investigator title: Principal Investigator: Fabiana Cristina Rosa Mitelmão
mesh term: Constipation