<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/NCT02972567</url>
  </required_header>
  <id_info>
    <org_study_id>P3600</org_study_id>
    <nct_id>NCT02972567</nct_id>
  </id_info>
  <brief_title>Evaluation of the Effects of a L.Reuteri Strain on Markers of Inflammation, Cardiovascular Risk and Fatty Liver Disease</brief_title>
  <acronym>PROSIR</acronym>
  <official_title>Evaluation of the Effect of a Lactobacillus Reuteri Strain on Markers of Inflammation, Cardiovascular Risk and Fatty Liver Disease in Obese Subjects With Insulin Resistance</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Biosearch S.A.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Universidad de Granada</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Complejo Hospitalario de Jaen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Biosearch S.A.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is the evaluation of the effects in obese patients with metabolic&#xD;
      syndrome on the composition of the intestinal microbiota, markers of the syndrome&#xD;
      (hypertension, dyslipidemia, inflammation biomarkers, risk cardiovascular and hepatic&#xD;
      steatosis) and other possible metabolites involved.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Randomized double blind crossover placebo controlled intervention study&#xD;
&#xD;
      The proposed study will be conducted by members of the Endocrinology and Nutrition Services&#xD;
      (ENCHJ), and Gastroenterology (ADCHJ), of the Hospital of Jaen and members of the Department&#xD;
      of Biochemistry and Molecular Biology II of the University of Granada (UGR) and members of&#xD;
      Microbiology Department of the University Hospital San Cecilio of Granada (MHUSC).&#xD;
&#xD;
      The selection, clinical and anthropometric control, general biochemical parameters and the&#xD;
      determination of hepatic steatosis by ultrasound will be performed by members of ENCHJ.&#xD;
&#xD;
      The determination of the composition of the intestinal microbiota will be carried out by&#xD;
      members of the UGR together with members form the MHUSC. Inflammation and steatosis&#xD;
      biomarkers as well as metabolic profile will be performed by members of the UGR.&#xD;
&#xD;
      The study will be conducted according to the Helsinki Rules and will be previously approved&#xD;
      by the Ethics Committee of Research of Jaen. The study will follow the rules of&#xD;
      international, national and regional research The biological samples will be managed and&#xD;
      processed in accordance with the research protocols by the Biobanco del Sistema Sanitario&#xD;
      Público de Andalucía. At the end of the project, samples will be stored within the framework&#xD;
      of Biobank from Public Health Organization of Andalusia .&#xD;
&#xD;
      The present study involves access and use of information confidential, so all the data will&#xD;
      be treated anonymously.&#xD;
&#xD;
      • Sample size assessment to specify the number of participants or participant years necessary&#xD;
      to demonstrate an effect.&#xD;
&#xD;
      Based on the range and median value on plasma lipopolysaccharide (LPS), and assuming a power&#xD;
      of 90% and a type error alpha of 5%, the minimum number of subjects was 32. To avoid possible&#xD;
      bias caused by gender and taking into account the withdrawal, will be recruited 60 subjects.&#xD;
&#xD;
      The missing data will be considered as unavailable data.&#xD;
&#xD;
      All statistical analyses will be performed using the statistical package SPSS (Statistical&#xD;
      Product and Service Solutions). Normally distributed data will be expressed as the mean and&#xD;
      standard error of the mean, whereas median and ranges will be used for data not normally&#xD;
      distributed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>May 2016</start_date>
  <completion_date type="Actual">December 2017</completion_date>
  <primary_completion_date type="Actual">December 2017</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>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from basal plasma lipopolysaccharide (LPS) at 12 weeks</measure>
    <time_frame>Basal (T0), 12 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from basal Blood pressure at 12 weeks</measure>
    <time_frame>Basal (T0), 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from basal HOMA ( homeostatic model assessment ) index at 12 weeks</measure>
    <time_frame>Basal (T0), 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from basal plasma cholesterol level (total, LDL and HDL) at 12 weeks</measure>
    <time_frame>Basal (T0), 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from basal plasma Inflammatory markers (sVCAM, sICAM, myeloperoxidase selectin, adiponectin, plasminogen activator inhibitor and resistin, and interleukines Il-6, Il-8, tumor necrosis factor, HGF, leptin and Multicopper oxidase-1) at 12 weeks</measure>
    <time_frame>Basal (T0), 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from basal Hepatic Steatosis markers (arginase, prolidase and RBP-4(Retinol binding protein-4)) at 12 weeks</measure>
    <time_frame>Basal (T0), 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from basal fecal microbiota at 12 weeks</measure>
    <time_frame>Basal (T0), 12 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Metabolic Syndrome X</condition>
  <arm_group>
    <arm_group_label>Probiotic</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Lactobacillus strain</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Maltodextrin</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Lactobacillus spp</intervention_name>
    <description>9 log10 cfu/capsule. 1 capsule/day for 12 weeks</description>
    <arm_group_label>Probiotic</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Control</intervention_name>
    <description>Maltodextrin</description>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with a diagnosis of insulin resistance syndrome, according to Criteria of the&#xD;
             International Diabetes Federation (IDF)&#xD;
&#xD;
          -  BMI&gt;30 kg/m2 or Waist Circumference ≥ 94cm (men) WC≥ 80cm (women)&#xD;
&#xD;
          -  Serum Triglycerides ≥ 150 mg/dl&#xD;
&#xD;
          -  HDLcholesterol &lt; 40 mg/dl (1,03 mmol/l) in men and &lt; 50 mg/dl (1,29 mmol/l) in women&#xD;
&#xD;
          -  Systolic blood pressure ≥ 130 mmHg or diastolic ≥ 85 mmHg&#xD;
&#xD;
          -  Glucose ≥ 100 mg/dl (5,6 mmol/l) (not previous diagnostic of diabetes II)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with renal or hepatic impairment&#xD;
&#xD;
          -  Patients with a diagnosis of diabetes&#xD;
&#xD;
          -  Patients with diseases that condition immunosuppression&#xD;
&#xD;
          -  Patients presenting positive serologies for liver viruses&#xD;
&#xD;
          -  Being on antihypertensive treatment: beta-blockers, Angiotensin 2 receptor antagonists&#xD;
             (ARA 2), enzyme inhibitors, Angiotensin converting enzyme (ACE) inhibitors.&#xD;
&#xD;
          -  Patients receiving lipid-lowering and / or hypoglycemic agents&#xD;
&#xD;
          -  Patients on treatment with drugs that increase hepatic enzymes,such as Amiodarone,&#xD;
             perhexiline, maleate and 4,4'-diethylaminoethoxyhexestrol, synthetic estrogens,&#xD;
             Tamoxifen, corticosteroids, acetylsalicylic acid, Valproic acid, tetracyclines, viral&#xD;
             agents (zidovudine, zalcitabine, didanosine), among others.&#xD;
&#xD;
          -  Exhibiting high values of C-reactive protein (CRP) or Sedimentation (ESR)&#xD;
&#xD;
          -  Consuming alcohol in quantities greater than 40 g / d or other hepatotoxic.&#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>Gil Ángel, Prof. Ph.D</last_name>
    <role>Study Director</role>
    <affiliation>University of Granada (Spain)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Complejo Hospitalario Universitario de Jaen</name>
      <address>
        <city>Jaen</city>
        <zip>23007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <results_reference>
    <citation>Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006 Dec 21;444(7122):1027-31. doi: 10.1038/nature05414.</citation>
    <PMID>17183312</PMID>
  </results_reference>
  <results_reference>
    <citation>Backhed F, Manchester JK, Semenkovich CF, Gordon JI. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):979-84. doi: 10.1073/pnas.0605374104. Epub 2007 Jan 8.</citation>
    <PMID>17210919</PMID>
  </results_reference>
  <results_reference>
    <citation>Bermudez-Brito M, Munoz-Quezada S, Gomez-Llorente C, Matencio E, Bernal MJ, Romero F, Gil A. Human intestinal dendritic cells decrease cytokine release against Salmonella infection in the presence of Lactobacillus paracasei upon TLR activation. PLoS One. 2012;7(8):e43197. doi: 10.1371/journal.pone.0043197. Epub 2012 Aug 14.</citation>
    <PMID>22905233</PMID>
  </results_reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>November 17, 2016</study_first_submitted>
  <study_first_submitted_qc>November 21, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 23, 2016</study_first_posted>
  <last_update_submitted>July 10, 2020</last_update_submitted>
  <last_update_submitted_qc>July 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 13, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>probiotics</keyword>
  <keyword>metabolic syndrome</keyword>
  <keyword>non-alcoholic fatty liver disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Diseases</mesh_term>
    <mesh_term>Fatty Liver</mesh_term>
    <mesh_term>Metabolic Syndrome</mesh_term>
    <mesh_term>Inflammation</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/NCT02972567
org study id: P3600
nct id: NCT02972567
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
The purpose of this study is the evaluation of the effects in obese patients with metabolic
      syndrome on the composition of the intestinal microbiota, markers of the syndrome
      (hypertension, dyslipidemia, inflammation biomarkers, risk cardiovascular and hepatic
      steatosis) and other possible metabolites involved.
Randomized double blind crossover placebo controlled intervention study

      The proposed study will be conducted by members of the Endocrinology and Nutrition Services
      (ENCHJ), and Gastroenterology (ADCHJ), of the Hospital of Jaen and members of the Department
      of Biochemistry and Molecular Biology II of the University of Granada (UGR) and members of
      Microbiology Department of the University Hospital San Cecilio of Granada (MHUSC).

      The selection, clinical and anthropometric control, general biochemical parameters and the
      determination of hepatic steatosis by ultrasound will be performed by members of ENCHJ.

      The determination of the composition of the intestinal microbiota will be carried out by
      members of the UGR together with members form the MHUSC. Inflammation and steatosis
      biomarkers as well as metabolic profile will be performed by members of the UGR.

      The study will be conducted according to the Helsinki Rules and will be previously approved
      by the Ethics Committee of Research of Jaen. The study will follow the rules of
      international, national and regional research The biological samples will be managed and
      processed in accordance with the research protocols by the Biobanco del Sistema Sanitario
      Público de Andalucía. At the end of the project, samples will be stored within the framework
      of Biobank from Public Health Organization of Andalusia .

      The present study involves access and use of information confidential, so all the data will
      be treated anonymously.

      • Sample size assessment to specify the number of participants or participant years necessary
      to demonstrate an effect.

      Based on the range and median value on plasma lipopolysaccharide (LPS), and assuming a power
      of 90% and a type error alpha of 5%, the minimum number of subjects was 32. To avoid possible
      bias caused by gender and taking into account the withdrawal, will be recruited 60 subjects.

      The missing data will be considered as unavailable data.

      All statistical analyses will be performed using the statistical package SPSS (Statistical
      Product and Service Solutions). Normally distributed data will be expressed as the mean and
      standard error of the mean, whereas median and ranges will be used for data not normally
      distributed.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change from basal plasma lipopolysaccharide (LPS) at 12 weeks
time frame: Basal (T0), 12 weeks
measure: Change from basal Blood pressure at 12 weeks
time frame: Basal (T0), 12 weeks
measure: Change from basal HOMA ( homeostatic model assessment ) index at 12 weeks
time frame: Basal (T0), 12 weeks
measure: Change from basal plasma cholesterol level (total, LDL and HDL) at 12 weeks
time frame: Basal (T0), 12 weeks
measure: Change from basal plasma Inflammatory markers (sVCAM, sICAM, myeloperoxidase selectin, adiponectin, plasminogen activator inhibitor and resistin, and interleukines Il-6, Il-8, tumor necrosis factor, HGF, leptin and Multicopper oxidase-1) at 12 weeks
time frame: Basal (T0), 12 weeks
measure: Change from basal Hepatic Steatosis markers (arginase, prolidase and RBP-4(Retinol binding protein-4)) at 12 weeks
time frame: Basal (T0), 12 weeks
measure: Changes from basal fecal microbiota at 12 weeks
time frame: Basal (T0), 12 weeks
arm group label: Probiotic
arm group type: Experimental
description: Lactobacillus strain
arm group label: Control
arm group type: Placebo Comparator
description: Maltodextrin
intervention type: Dietary Supplement
intervention name: Lactobacillus spp
description: 9 log10 cfu/capsule. 1 capsule/day for 12 weeks
arm group label: Probiotic
intervention type: Dietary Supplement
intervention name: Control
description: Maltodextrin
arm group label: Control
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Gil Ángel, Prof. Ph.D
role: Study Director
affiliation: University of Granada (Spain)
facility: 
country: Spain
citation: Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006 Dec 21;444(7122):1027-31. doi: 10.1038/nature05414.
PMID: 17183312
citation: Backhed F, Manchester JK, Semenkovich CF, Gordon JI. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):979-84. doi: 10.1073/pnas.0605374104. Epub 2007 Jan 8.
PMID: 17210919
citation: Bermudez-Brito M, Munoz-Quezada S, Gomez-Llorente C, Matencio E, Bernal MJ, Romero F, Gil A. Human intestinal dendritic cells decrease cytokine release against Salmonella infection in the presence of Lactobacillus paracasei upon TLR activation. PLoS One. 2012;7(8):e43197. doi: 10.1371/journal.pone.0043197. Epub 2012 Aug 14.
PMID: 22905233
responsible party type: Sponsor
mesh term: Liver Diseases
mesh term: Fatty Liver
mesh term: Metabolic Syndrome
mesh term: Inflammation
sharing ipd: No