<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/NCT03274648</url>
  </required_header>
  <id_info>
    <org_study_id>butyrate2017</org_study_id>
    <nct_id>NCT03274648</nct_id>
  </id_info>
  <brief_title>Dietary Interventions and Butyrate Production in Behçet's Patients</brief_title>
  <official_title>Therapeutic Modulation of Butyrate Production in Behçet's Patients: a Dietary Intervention Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Azienda Ospedaliero-Universitaria Careggi</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Azienda Ospedaliero-Universitaria Careggi</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      A dietary intervention trial will be performed on patients affected by Behçet's syndrome.&#xD;
      Three different diets will be compared, analyzing their effects on the gut microbiota&#xD;
      composition, on endogenous butyrate production and on the general symptoms in Behçet's&#xD;
      patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A dietary intervention trial will be conducted with the use of three different diets in order&#xD;
      to compare the effects of these diets on the gut microbiota composition, on endogenous&#xD;
      butyrate production and on the general symptoms in Behçet's patients.&#xD;
&#xD;
      The study will be a randomized, open trial designed to test whether a vegetarian diet or an&#xD;
      habitual diet supplemented with oral butyrate would benefit the butyrate production, the gut&#xD;
      microbiota composition and the general symptoms of Behçet's patients, compared with the&#xD;
      habitual diet.&#xD;
&#xD;
      The study will involve 30 subjects with Behçet syndrome. Patients will be randomly assigned&#xD;
      to follow a 3-months isocaloric dietary profile with either:&#xD;
&#xD;
        -  vegetarian diet containing inulin and resistant starch-rich foods, including no meat and&#xD;
           fish, but containing eggs and dairy products&#xD;
&#xD;
        -  habitual diet supplemented with 2.4g/day of oral butyrate&#xD;
&#xD;
        -  habitual diet without supplementation At the baseline visit, subjects will be educated&#xD;
           about the aims and methods of the clinical trial and will sign their informed consent&#xD;
           form.&#xD;
&#xD;
      Anthropometric measurements, body composition, and blood and stool sampling will be obtained&#xD;
      from each participant at the beginning and at the end of the intervention period. All&#xD;
      subjects will be examined between 07.00 and 09.30 hours after a 12 h fasting period.&#xD;
&#xD;
      The following parameters will be analyzed both at the beginning and at the end of the&#xD;
      intervention period:&#xD;
&#xD;
        -  Complete blood count&#xD;
&#xD;
        -  Lipid variables - total cholesterol, low density lipoprotein cholesterol (LDL), high&#xD;
           density lipoprotein cholesterol (HDL), triglycerides&#xD;
&#xD;
        -  Glycemic profile - glucose, insulin, glycated hemoglobin (HbA1C), HOMA index&#xD;
&#xD;
        -  Liver function tests - aspartate aminotransferase (AST), alanine transaminase (ALT),&#xD;
           gammaglutamyl transferase (GGT), alkaline phosphatase (ALP), albumin, prealbumin&#xD;
&#xD;
        -  Kidney function tests - serum creatinine, urea, uric acid&#xD;
&#xD;
        -  Mineral profile - sodium, potassium, magnesium, calcium&#xD;
&#xD;
        -  Iron metabolism - iron, ferritin&#xD;
&#xD;
        -  Vitamin profile - vitamin B12, folic acid, vitamin D&#xD;
&#xD;
        -  Thyroid function - TSH&#xD;
&#xD;
        -  Inflammatory markers - erythrocyte sedimentation rate (ESR), C-reactive protein (CRP),&#xD;
           fibrinogen, serum amyloid A (SAA)&#xD;
&#xD;
        -  Serology for celiac disease - IgA, anti-transglutaminase antibodies (IgA), anti&#xD;
           endomysium antibodies (IgA)&#xD;
&#xD;
        -  Circulating levels of inflammatory cytokines&#xD;
&#xD;
        -  Oxidative stress markers&#xD;
&#xD;
        -  Gut microbiota composition&#xD;
&#xD;
        -  Butyrate production&#xD;
&#xD;
      At the beginning and at the end of the intervention period, participants will be asked to&#xD;
      complete a questionnaire, which will assess Behçet's symptoms frequency and severity. In&#xD;
      addition, participants will be contacted by phone to complete a 24-hours recall in order to&#xD;
      test the adherence to diets they have been assigned to.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 27, 2017</start_date>
  <completion_date type="Actual">July 5, 2019</completion_date>
  <primary_completion_date type="Actual">May 1, 2019</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>Behçet's will be assigned to one of the following treatments:&#xD;
vegetarian diet containing inulin and resistant starch-rich foods, including no meat and fish, but containing eggs and dairy products&#xD;
habitual diet supplemented with 2.4g/day of oral butyrate&#xD;
habitual diet without supplementation</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Evaluation of gut microbiota composition</measure>
    <time_frame>0-3 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Evaluation of butyrate production</measure>
    <time_frame>0-3 months</time_frame>
    <description>For the extraction of SCFAs (and butyrate in particular) the method described in Schnorr et al. will be follow&quot; [Schnorr SL, Candela M, Rampelli S, Centanni M, Consolandi C, Basaglia G,et al. Gut microbiome of the Hadza hunter-gatherers. Nat Commun 2014;5:3654]</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Complete blood count</measure>
    <time_frame>0-3 months</time_frame>
    <description>composite score</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Lipid variables</measure>
    <time_frame>0-3 months</time_frame>
    <description>composite score taking into account the levels of: total cholesterol, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), triglycerides</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Glycemic profile</measure>
    <time_frame>0-3 months</time_frame>
    <description>composite score taking into account the levels of : glucose, insulin, glycated hemoglobin (HbA1C), HOMA index</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Vitamin profile</measure>
    <time_frame>0-3 months</time_frame>
    <description>composite score, taking into account the levels of: vitamin B12, folic acid, vitamin D</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Liver function tests</measure>
    <time_frame>0-3 months</time_frame>
    <description>composite score taking into account the levels of: aspartate aminotransferase (AST), alanine transaminase (ALT), gammaglutamyl transferase (GGT), alkaline phosphatase (ALP), albumin, prealbumin</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Kidney function tests</measure>
    <time_frame>0-3 months</time_frame>
    <description>composite score taking into account the levels of : serum creatinine, urea, uric acid</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mineral profile</measure>
    <time_frame>0-3 months</time_frame>
    <description>composite score taking into account the levels of: sodium, potassium, magnesium, calcium</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Iron metabolism</measure>
    <time_frame>0-3 months</time_frame>
    <description>composite score taking into account the levels of: iron, ferritin</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Thyroid function</measure>
    <time_frame>0-3 months</time_frame>
    <description>measurement of TSH levels</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Inflammatory markers</measure>
    <time_frame>0-3 months</time_frame>
    <description>composite score taking into account the levels of: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fibrinogen, serum amyloid A (SAA)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Serology for celiac disease</measure>
    <time_frame>0-3 months</time_frame>
    <description>composite score taking into account the levels of: IgA, anti-transglutaminase antibodies (IgA), anti endomysium antibodies (IgA)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Circulating levels of inflammatory cytokines</measure>
    <time_frame>0-3 months</time_frame>
    <description>composite score</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Oxidative stress markers</measure>
    <time_frame>0-3 months</time_frame>
    <description>composite score</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluation Behçet's symptoms frequency and severity</measure>
    <time_frame>0-3 months</time_frame>
    <description>Participants are asked to complete a questionnaire, which will assess Behçet's symptoms frequency and severity.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">17</enrollment>
  <condition>Behcet Syndrome</condition>
  <arm_group>
    <arm_group_label>vegetarian diet</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>vegetarian diet containing inulin and resistant starch-rich foods, including no meat and fish, but containing eggs and dairy products</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Habitual diet + oral butyrate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>habitual diet supplemented with 2.4g/day of oral butyrate</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Habitual diet</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>habitual diet without supplementation</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Oral butyrate</intervention_name>
    <description>Patients follow the habitual diet supplemented with 2.4g/day of oral butyrate</description>
    <arm_group_label>Habitual diet + oral butyrate</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Vegetarian diet</intervention_name>
    <description>Patients follow a vegetarian diet containing inulin and resistant starch-rich foods, including no meat and fish, but containing eggs and dairy products</description>
    <arm_group_label>vegetarian diet</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Habitual diet</intervention_name>
    <description>Patients follow the habitual diet</description>
    <arm_group_label>Habitual diet</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All patients affected by Behçet's disease&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy or breastfeeding&#xD;
&#xD;
          -  Presence of diabetes mellitus&#xD;
&#xD;
          -  Presence of other immune-mediated diseases&#xD;
&#xD;
          -  Presence or history of cancer in the last 5 years&#xD;
&#xD;
          -  Presence of infectious diseases in the last 3 months&#xD;
&#xD;
          -  No antibiotic therapy in the last 3 months&#xD;
&#xD;
          -  No vegetarian or vegan diet&#xD;
&#xD;
          -  No intake of pro- or pre-biotics in the last 3 months&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>AOU Careggi</name>
      <address>
        <city>Florence</city>
        <zip>50134</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Skef W, Hamilton MJ, Arayssi T. Gastrointestinal Behcet's disease: a review. World J Gastroenterol. 2015 Apr 7;21(13):3801-12. doi: 10.3748/wjg.v21.i13.3801.</citation>
    <PMID>25852265</PMID>
  </reference>
  <reference>
    <citation>Consolandi C, Turroni S, Emmi G, Severgnini M, Fiori J, Peano C, Biagi E, Grassi A, Rampelli S, Silvestri E, Centanni M, Cianchi F, Gotti R, Emmi L, Brigidi P, Bizzaro N, De Bellis G, Prisco D, Candela M, D'Elios MM. Behcet's syndrome patients exhibit specific microbiome signature. Autoimmun Rev. 2015 Apr;14(4):269-76. doi: 10.1016/j.autrev.2014.11.009. Epub 2014 Nov 27.</citation>
    <PMID>25435420</PMID>
  </reference>
  <reference>
    <citation>Wong JM. Gut microbiota and cardiometabolic outcomes: influence of dietary patterns and their associated components. Am J Clin Nutr. 2014 Jul;100 Suppl 1:369S-77S. doi: 10.3945/ajcn.113.071639. Epub 2014 Jun 4.</citation>
    <PMID>24898225</PMID>
  </reference>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>August 31, 2017</study_first_submitted>
  <study_first_submitted_qc>September 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 7, 2017</study_first_posted>
  <last_update_submitted>January 27, 2020</last_update_submitted>
  <last_update_submitted_qc>January 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 28, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Azienda Ospedaliero-Universitaria Careggi</investigator_affiliation>
    <investigator_full_name>GIACOMO EMMI</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Behcet Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>IPD will not be shared</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/NCT03274648
org study id: butyrate2017
nct id: NCT03274648
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
A dietary intervention trial will be performed on patients affected by Behçet's syndrome.
      Three different diets will be compared, analyzing their effects on the gut microbiota
      composition, on endogenous butyrate production and on the general symptoms in Behçet's
      patients.
A dietary intervention trial will be conducted with the use of three different diets in order
      to compare the effects of these diets on the gut microbiota composition, on endogenous
      butyrate production and on the general symptoms in Behçet's patients.

      The study will be a randomized, open trial designed to test whether a vegetarian diet or an
      habitual diet supplemented with oral butyrate would benefit the butyrate production, the gut
      microbiota composition and the general symptoms of Behçet's patients, compared with the
      habitual diet.

      The study will involve 30 subjects with Behçet syndrome. Patients will be randomly assigned
      to follow a 3-months isocaloric dietary profile with either:

        -  vegetarian diet containing inulin and resistant starch-rich foods, including no meat and
           fish, but containing eggs and dairy products

        -  habitual diet supplemented with 2.4g/day of oral butyrate

        -  habitual diet without supplementation At the baseline visit, subjects will be educated
           about the aims and methods of the clinical trial and will sign their informed consent
           form.

      Anthropometric measurements, body composition, and blood and stool sampling will be obtained
      from each participant at the beginning and at the end of the intervention period. All
      subjects will be examined between 07.00 and 09.30 hours after a 12 h fasting period.

      The following parameters will be analyzed both at the beginning and at the end of the
      intervention period:

        -  Complete blood count

        -  Lipid variables - total cholesterol, low density lipoprotein cholesterol (LDL), high
           density lipoprotein cholesterol (HDL), triglycerides

        -  Glycemic profile - glucose, insulin, glycated hemoglobin (HbA1C), HOMA index

        -  Liver function tests - aspartate aminotransferase (AST), alanine transaminase (ALT),
           gammaglutamyl transferase (GGT), alkaline phosphatase (ALP), albumin, prealbumin

        -  Kidney function tests - serum creatinine, urea, uric acid

        -  Mineral profile - sodium, potassium, magnesium, calcium

        -  Iron metabolism - iron, ferritin

        -  Vitamin profile - vitamin B12, folic acid, vitamin D

        -  Thyroid function - TSH

        -  Inflammatory markers - erythrocyte sedimentation rate (ESR), C-reactive protein (CRP),
           fibrinogen, serum amyloid A (SAA)

        -  Serology for celiac disease - IgA, anti-transglutaminase antibodies (IgA), anti
           endomysium antibodies (IgA)

        -  Circulating levels of inflammatory cytokines

        -  Oxidative stress markers

        -  Gut microbiota composition

        -  Butyrate production

      At the beginning and at the end of the intervention period, participants will be asked to
      complete a questionnaire, which will assess Behçet's symptoms frequency and severity. In
      addition, participants will be contacted by phone to complete a 24-hours recall in order to
      test the adherence to diets they have been assigned to.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Behçet's will be assigned to one of the following treatments:
vegetarian diet containing inulin and resistant starch-rich foods, including no meat and fish, but containing eggs and dairy products
habitual diet supplemented with 2.4g/day of oral butyrate
habitual diet without supplementation
primary purpose: Treatment
masking: None (Open Label)
measure: Evaluation of gut microbiota composition
time frame: 0-3 months
measure: Evaluation of butyrate production
time frame: 0-3 months
description: For the extraction of SCFAs (and butyrate in particular) the method described in Schnorr et al. will be follow" [Schnorr SL, Candela M, Rampelli S, Centanni M, Consolandi C, Basaglia G,et al. Gut microbiome of the Hadza hunter-gatherers. Nat Commun 2014;5:3654]
measure: Complete blood count
time frame: 0-3 months
description: composite score
measure: Lipid variables
time frame: 0-3 months
description: composite score taking into account the levels of: total cholesterol, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), triglycerides
measure: Glycemic profile
time frame: 0-3 months
description: composite score taking into account the levels of : glucose, insulin, glycated hemoglobin (HbA1C), HOMA index
measure: Vitamin profile
time frame: 0-3 months
description: composite score, taking into account the levels of: vitamin B12, folic acid, vitamin D
measure: Liver function tests
time frame: 0-3 months
description: composite score taking into account the levels of: aspartate aminotransferase (AST), alanine transaminase (ALT), gammaglutamyl transferase (GGT), alkaline phosphatase (ALP), albumin, prealbumin
measure: Kidney function tests
time frame: 0-3 months
description: composite score taking into account the levels of : serum creatinine, urea, uric acid
measure: Mineral profile
time frame: 0-3 months
description: composite score taking into account the levels of: sodium, potassium, magnesium, calcium
measure: Iron metabolism
time frame: 0-3 months
description: composite score taking into account the levels of: iron, ferritin
measure: Thyroid function
time frame: 0-3 months
description: measurement of TSH levels
measure: Inflammatory markers
time frame: 0-3 months
description: composite score taking into account the levels of: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fibrinogen, serum amyloid A (SAA)
measure: Serology for celiac disease
time frame: 0-3 months
description: composite score taking into account the levels of: IgA, anti-transglutaminase antibodies (IgA), anti endomysium antibodies (IgA)
measure: Circulating levels of inflammatory cytokines
time frame: 0-3 months
description: composite score
measure: Oxidative stress markers
time frame: 0-3 months
description: composite score
measure: Evaluation Behçet's symptoms frequency and severity
time frame: 0-3 months
description: Participants are asked to complete a questionnaire, which will assess Behçet's symptoms frequency and severity.
arm group label: vegetarian diet
arm group type: Experimental
description: vegetarian diet containing inulin and resistant starch-rich foods, including no meat and fish, but containing eggs and dairy products
arm group label: Habitual diet + oral butyrate
arm group type: Experimental
description: habitual diet supplemented with 2.4g/day of oral butyrate
arm group label: Habitual diet
arm group type: Active Comparator
description: habitual diet without supplementation
intervention type: Dietary Supplement
intervention name: Oral butyrate
description: Patients follow the habitual diet supplemented with 2.4g/day of oral butyrate
arm group label: Habitual diet + oral butyrate
intervention type: Dietary Supplement
intervention name: Vegetarian diet
description: Patients follow a vegetarian diet containing inulin and resistant starch-rich foods, including no meat and fish, but containing eggs and dairy products
arm group label: vegetarian diet
intervention type: Dietary Supplement
intervention name: Habitual diet
description: Patients follow the habitual diet
arm group label: Habitual diet
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
facility: 
country: Italy
citation: Skef W, Hamilton MJ, Arayssi T. Gastrointestinal Behcet's disease: a review. World J Gastroenterol. 2015 Apr 7;21(13):3801-12. doi: 10.3748/wjg.v21.i13.3801.
PMID: 25852265
citation: Consolandi C, Turroni S, Emmi G, Severgnini M, Fiori J, Peano C, Biagi E, Grassi A, Rampelli S, Silvestri E, Centanni M, Cianchi F, Gotti R, Emmi L, Brigidi P, Bizzaro N, De Bellis G, Prisco D, Candela M, D'Elios MM. Behcet's syndrome patients exhibit specific microbiome signature. Autoimmun Rev. 2015 Apr;14(4):269-76. doi: 10.1016/j.autrev.2014.11.009. Epub 2014 Nov 27.
PMID: 25435420
citation: Wong JM. Gut microbiota and cardiometabolic outcomes: influence of dietary patterns and their associated components. Am J Clin Nutr. 2014 Jul;100 Suppl 1:369S-77S. doi: 10.3945/ajcn.113.071639. Epub 2014 Jun 4.
PMID: 24898225
responsible party type: Principal Investigator
investigator affiliation: Azienda Ospedaliero-Universitaria Careggi
investigator full name: GIACOMO EMMI
investigator title: Principal Investigator
mesh term: Behcet Syndrome
sharing ipd: No
ipd description: IPD will not be shared