<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/NCT03021161</url>
  </required_header>
  <id_info>
    <org_study_id>548/2016</org_study_id>
    <nct_id>NCT03021161</nct_id>
  </id_info>
  <brief_title>The Effect of Probiotics on Asthma Risk in Animal Laboratory Workers</brief_title>
  <acronym>prob&amp;asthma</acronym>
  <official_title>The Effect of Probiotics on Asthma Risk in Animal Laboratory Workers: A Randomized Controlled Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Sao Paulo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Sao Paulo General Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Sao Paulo</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This project will be test the effect of probiotics on occupational allergic sensitization,&#xD;
      respiratory symptoms and bronchial hyperresponsiveness in workers or students that develop&#xD;
      respiratory symptoms exposed to laboratory animals, i.e., small rodents.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      INTRODUCTION: The objective of the present project is to test the effect of probiotics on&#xD;
      occupational allergic sensitization, respiratory symptoms and bronchial hyperresponsiveness&#xD;
      in workers or students exposed to laboratory animals, i.e., small rodents.&#xD;
&#xD;
      Furthermore, our study aims to determine changes in immunological patterns with the use of&#xD;
      probiotics in adulthood, which could prevent allergic sensitization and allergic diseases.&#xD;
&#xD;
      Probiotics have been used as treatment in various allergic diseases, especially as prevention&#xD;
      of child atopic dermatitis by using them during pregnancy, or for neonates and infants.&#xD;
&#xD;
      STUDY DESIGN AND METHODS: This will be a randomized controlled trial involving laboratory&#xD;
      animal workers and students exposed to rats, mice, hamsters, guinea pigs or rabbits. Subjects&#xD;
      will be recruited in the laboratories of the University of S. Paulo and State University of&#xD;
      Campinas (Unicamp). Exposed subjects will be randomly allocated to two groups: treatment and&#xD;
      placebo. Both groups will be followed up for two years. Subjects will be evaluated at&#xD;
      baseline, after one year and after two years.&#xD;
&#xD;
      Treatment: the intervention group will receive once daily capsules containing 109 CFU of&#xD;
      Lactobacillus rhamnosus HN001, Lactobacillus paracasei Lpc-37 and Bifidobacterium animalis&#xD;
      ssp. Lactis HN019 and the control group will receive once daily similar capsules containing&#xD;
      placebo.&#xD;
&#xD;
      Procedures: blood sampling for blood cell counts, measurement of total IgE levels, specific&#xD;
      immunoglobulin E (IgE) for rats, mice, hamsters, guinea pigs and rabbits; stool samples to&#xD;
      test for parasites and for probiotic bacteria; skin prick test for animal allergens and&#xD;
      common allergens, i.e. cockroaches, house dust mites, cats, dogs and mixed fungi; spirometry;&#xD;
      and evaluation of bronchial responsiveness by bronchial challenge tests if the participant&#xD;
      develop respiratory symptoms.&#xD;
&#xD;
      At the end of two years, changes in sensitization, bronchial responsiveness or symptoms in&#xD;
      the treatment group compared to the placebo group will be considered the effect of&#xD;
      probiotics.&#xD;
&#xD;
      Data analysis: group results will be compared by the chi-squared test regarding the&#xD;
      prevalence of sensitization and other categorical variables. For continuous variables such as&#xD;
      IgE levels, comparisons will be made by Student's t test. These analyses will be performed at&#xD;
      the 1- and 2-year time points.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>January 2017</start_date>
  <completion_date type="Anticipated">January 2020</completion_date>
  <primary_completion_date type="Anticipated">December 2017</primary_completion_date>
  <phase>Phase 4</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>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>detection the reduction of sensitization in workers exposed to laboratory animal</measure>
    <time_frame>two years</time_frame>
    <description>To compare the effect of the oral administration of probiotics on the development of occupational sensitization to the effect of a placebo. Sensitization will be assessed by prick test and specific IgE.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assessment of symptoms</measure>
    <time_frame>two years</time_frame>
    <description>All subjects will respond to the respiratory symptoms questionnaire of the European Community Respiratory Health Survey (ECRHS), translated and validated by Ribeiro et al. (2007). In addition, both groups will respond to a questionnaire about symptoms of allergic rhinitis, asthma and allergic skin disease, previous exposure to laboratory animals, a personal and family history of allergic diseases, as well as gastrointestinal, urinary and infectious symptoms</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Asthma Occupational</condition>
  <arm_group>
    <arm_group_label>intervention group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The intervention group will receive once daily capsules containing 109 CFU of Lactobacillus rhamnosus HN001, Lactobacillus paracasei Lpc-37 and Bifidobacterium animalis ssp. Lactis HN019 (probiotic formula).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Oral Capsule</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The control group will receive once daily similar capsules containing placebo.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Probiotic Formula</intervention_name>
    <description>The intervention group will receive once daily capsules containing 109 CFU of Lactobacillus rhamnosus HN001, Lactobacillus paracasei Lpc-37 and Bifidobacterium animalis ssp. Lactis HN019</description>
    <arm_group_label>intervention group</arm_group_label>
    <other_name>L. rhamnosus, L. paracasei, B. Lactis</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo Oral Capsule</intervention_name>
    <description>Capsule containing no probiotic</description>
    <arm_group_label>Placebo Oral Capsule</arm_group_label>
    <other_name>Probiotic diluent</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Older than 18 years, both sexes, ability to read, understand and to decide on protocol&#xD;
             consenting.&#xD;
&#xD;
          -  Participants should be healthy&#xD;
&#xD;
          -  Animal handling for research purposes as part of regular activities as a worker or&#xD;
             student.&#xD;
&#xD;
          -  Planning to continue this activity for the next 2 years.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous laboratory animal handling for 15 days or longer. This exposure may have&#xD;
             sensitized or selected people that are not susceptible to sensitizations.&#xD;
&#xD;
          -  Sensitization to any laboratory animal (rat, mouse, hamster, guinea pig or rabbit).&#xD;
&#xD;
          -  Allergic diseases that interfere with the evaluation of study variables.&#xD;
&#xD;
          -  Using immunosuppressive drugs (ex: methotrexate, cyclosporine, leflunomide) or&#xD;
             corticosteroids in immunosuppressive doses (e.g.: prednisone doses of 1.0 mg/kg/day or&#xD;
             more).&#xD;
&#xD;
          -  Cancer or treatment of neoplasia.&#xD;
&#xD;
          -  Having diseases that cause immunosuppression such as diabetes, AIDS, renal failure,&#xD;
             heart failure or other organ failure.&#xD;
&#xD;
          -  Pregnancy, breastfeeding, or not willing to take necessary precautions to avoid a&#xD;
             pregnancy during the study.&#xD;
&#xD;
          -  Use of other probiotic products during the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Elcio O Vianna, MD, PHD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of S. Paulo Medical School of Rib. Preto</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Elcio O Vianna, MD, PHD</last_name>
    <phone>55-16-36022706</phone>
    <email>evianna@fmrp.usp.br</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Rosangela V Garcia, MD</last_name>
    <phone>55-16-36021800</phone>
    <email>rosangelavillela@yahoo.com.br</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University Hospital of Ribeirao Preto</name>
      <address>
        <city>Ribeirao Preto</city>
        <state>Sao Paulo</state>
        <zip>14048900</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <contact>
      <last_name>Elcio O Vianna, MD, PHD</last_name>
      <phone>55-16-3602-2706</phone>
      <email>evianna@fmrp.usp.br</email>
    </contact>
    <contact_backup>
      <last_name>Rosangela V Garcia, MD</last_name>
      <phone>55-16-36021800</phone>
      <email>rosangelavillela@yahoo.com.br</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
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    <citation>Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A, Zuberbier T, Baena-Cagnani CE, Canonica GW, van Weel C, Agache I, Ait-Khaled N, Bachert C, Blaiss MS, Bonini S, Boulet LP, Bousquet PJ, Camargos P, Carlsen KH, Chen Y, Custovic A, Dahl R, Demoly P, Douagui H, Durham SR, van Wijk RG, Kalayci O, Kaliner MA, Kim YY, Kowalski ML, Kuna P, Le LT, Lemiere C, Li J, Lockey RF, Mavale-Manuel S, Meltzer EO, Mohammad Y, Mullol J, Naclerio R, O'Hehir RE, Ohta K, Ouedraogo S, Palkonen S, Papadopoulos N, Passalacqua G, Pawankar R, Popov TA, Rabe KF, Rosado-Pinto J, Scadding GK, Simons FE, Toskala E, Valovirta E, van Cauwenberge P, Wang DY, Wickman M, Yawn BP, Yorgancioglu A, Yusuf OM, Zar H, Annesi-Maesano I, Bateman ED, Ben Kheder A, Boakye DA, Bouchard J, Burney P, Busse WW, Chan-Yeung M, Chavannes NH, Chuchalin A, Dolen WK, Emuzyte R, Grouse L, Humbert M, Jackson C, Johnston SL, Keith PK, Kemp JP, Klossek JM, Larenas-Linnemann D, Lipworth B, Malo JL, Marshall GD, Naspitz C, Nekam K, Niggemann B, Nizankowska-Mogilnicka E, Okamoto Y, Orru MP, Potter P, Price D, Stoloff SW, Vandenplas O, Viegi G, Williams D; World Health Organization; GA(2)LEN; AllerGen. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy. 2008 Apr;63 Suppl 86:8-160. doi: 10.1111/j.1398-9995.2007.01620.x. No abstract available.</citation>
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    <citation>Bousquet J, Schunemann HJ, Zuberbier T, Bachert C, Baena-Cagnani CE, Bousquet PJ, Brozek J, Canonica GW, Casale TB, Demoly P, Gerth van Wijk R, Ohta K, Bateman ED, Calderon M, Cruz AA, Dolen WK, Haughney J, Lockey RF, Lotvall J, O'Byrne P, Spranger O, Togias A, Bonini S, Boulet LP, Camargos P, Carlsen KH, Chavannes NH, Delgado L, Durham SR, Fokkens WJ, Fonseca J, Haahtela T, Kalayci O, Kowalski ML, Larenas-Linnemann D, Li J, Mohammad Y, Mullol J, Naclerio R, O'Hehir RE, Papadopoulos N, Passalacqua G, Rabe KF, Pawankar R, Ryan D, Samolinski B, Simons FE, Valovirta E, Yorgancioglu A, Yusuf OM, Agache I, Ait-Khaled N, Annesi-Maesano I, Beghe B, Ben Kheder A, Blaiss MS, Boakye DA, Bouchard J, Burney PG, Busse WW, Chan-Yeung M, Chen Y, Chuchalin AG, Costa DJ, Custovic A, Dahl R, Denburg J, Douagui H, Emuzyte R, Grouse L, Humbert M, Jackson C, Johnston SL, Kaliner MA, Keith PK, Kim YY, Klossek JM, Kuna P, Le LT, Lemiere C, Lipworth B, Mahboub B, Malo JL, Marshall GD, Mavale-Manuel S, Meltzer EO, Morais-Almeida M, Motala C, Naspitz C, Nekam K, Niggemann B, Nizankowska-Mogilnicka E, Okamoto Y, Orru MP, Ouedraogo S, Palkonen S, Popov TA, Price D, Rosado-Pinto J, Scadding GK, Sooronbaev TM, Stoloff SW, Toskala E, van Cauwenberge P, Vandenplas O, van Weel C, Viegi G, Virchow JC, Wang DY, Wickman M, Williams D, Yawn BP, Zar HJ, Zernotti M, Zhong N; WHO Collaborating Center of Asthma and Rhinitis (Montpellier). Development and implementation of guidelines in allergic rhinitis - an ARIA-GA2LEN paper. Allergy. 2010 Oct;65(10):1212-21. doi: 10.1111/j.1398-9995.2010.02439.x.</citation>
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  <verification_date>January 2017</verification_date>
  <study_first_submitted>January 11, 2017</study_first_submitted>
  <study_first_submitted_qc>January 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 13, 2017</study_first_posted>
  <last_update_submitted>January 11, 2017</last_update_submitted>
  <last_update_submitted_qc>January 11, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 13, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Sao Paulo</investigator_affiliation>
    <investigator_full_name>Elcio Vianna</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>probiotic</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Asthma</mesh_term>
    <mesh_term>Asthma, Occupational</mesh_term>
  </condition_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/NCT03021161
org study id: 548/2016
nct id: NCT03021161
lead sponsor: 
collaborator: 
has dmc: Yes
This project will be test the effect of probiotics on occupational allergic sensitization,
      respiratory symptoms and bronchial hyperresponsiveness in workers or students that develop
      respiratory symptoms exposed to laboratory animals, i.e., small rodents.
INTRODUCTION: The objective of the present project is to test the effect of probiotics on
      occupational allergic sensitization, respiratory symptoms and bronchial hyperresponsiveness
      in workers or students exposed to laboratory animals, i.e., small rodents.

      Furthermore, our study aims to determine changes in immunological patterns with the use of
      probiotics in adulthood, which could prevent allergic sensitization and allergic diseases.

      Probiotics have been used as treatment in various allergic diseases, especially as prevention
      of child atopic dermatitis by using them during pregnancy, or for neonates and infants.

      STUDY DESIGN AND METHODS: This will be a randomized controlled trial involving laboratory
      animal workers and students exposed to rats, mice, hamsters, guinea pigs or rabbits. Subjects
      will be recruited in the laboratories of the University of S. Paulo and State University of
      Campinas (Unicamp). Exposed subjects will be randomly allocated to two groups: treatment and
      placebo. Both groups will be followed up for two years. Subjects will be evaluated at
      baseline, after one year and after two years.

      Treatment: the intervention group will receive once daily capsules containing 109 CFU of
      Lactobacillus rhamnosus HN001, Lactobacillus paracasei Lpc-37 and Bifidobacterium animalis
      ssp. Lactis HN019 and the control group will receive once daily similar capsules containing
      placebo.

      Procedures: blood sampling for blood cell counts, measurement of total IgE levels, specific
      immunoglobulin E (IgE) for rats, mice, hamsters, guinea pigs and rabbits; stool samples to
      test for parasites and for probiotic bacteria; skin prick test for animal allergens and
      common allergens, i.e. cockroaches, house dust mites, cats, dogs and mixed fungi; spirometry;
      and evaluation of bronchial responsiveness by bronchial challenge tests if the participant
      develop respiratory symptoms.

      At the end of two years, changes in sensitization, bronchial responsiveness or symptoms in
      the treatment group compared to the placebo group will be considered the effect of
      probiotics.

      Data analysis: group results will be compared by the chi-squared test regarding the
      prevalence of sensitization and other categorical variables. For continuous variables such as
      IgE levels, comparisons will be made by Student's t test. These analyses will be performed at
      the 1- and 2-year time points.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Participant, Investigator)
measure: detection the reduction of sensitization in workers exposed to laboratory animal
time frame: two years
description: To compare the effect of the oral administration of probiotics on the development of occupational sensitization to the effect of a placebo. Sensitization will be assessed by prick test and specific IgE.
measure: Assessment of symptoms
time frame: two years
description: All subjects will respond to the respiratory symptoms questionnaire of the European Community Respiratory Health Survey (ECRHS), translated and validated by Ribeiro et al. (2007). In addition, both groups will respond to a questionnaire about symptoms of allergic rhinitis, asthma and allergic skin disease, previous exposure to laboratory animals, a personal and family history of allergic diseases, as well as gastrointestinal, urinary and infectious symptoms
arm group label: intervention group
arm group type: Experimental
description: The intervention group will receive once daily capsules containing 109 CFU of Lactobacillus rhamnosus HN001, Lactobacillus paracasei Lpc-37 and Bifidobacterium animalis ssp. Lactis HN019 (probiotic formula).
arm group label: Placebo Oral Capsule
arm group type: Placebo Comparator
description: The control group will receive once daily similar capsules containing placebo.
intervention type: Drug
intervention name: Probiotic Formula
description: The intervention group will receive once daily capsules containing 109 CFU of Lactobacillus rhamnosus HN001, Lactobacillus paracasei Lpc-37 and Bifidobacterium animalis ssp. Lactis HN019
arm group label: intervention group
other name: L. rhamnosus, L. paracasei, B. Lactis
intervention type: Other
intervention name: Placebo Oral Capsule
description: Capsule containing no probiotic
arm group label: Placebo Oral Capsule
other name: Probiotic diluent
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Elcio O Vianna, MD, PHD
role: Principal Investigator
affiliation: University of S. Paulo Medical School of Rib. Preto
last name: Elcio O Vianna, MD, PHD
phone: 55-16-36022706
email: evianna@fmrp.usp.br
last name: Rosangela V Garcia, MD
phone: 55-16-36021800
email: rosangelavillela@yahoo.com.br
facility: 
contact: 
contact backup: 
country: Brazil
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PMID: 20887423
responsible party type: Principal Investigator
investigator affiliation: University of Sao Paulo
investigator full name: Elcio Vianna
investigator title: Principal Investigator
mesh term: Asthma
mesh term: Asthma, Occupational
sharing ipd: No