<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/NCT04491266</url>
  </required_header>
  <id_info>
    <org_study_id>20-13</org_study_id>
    <nct_id>NCT04491266</nct_id>
  </id_info>
  <brief_title>Tolerability and Modulatory Action of the Butyrate Releaser N-(1-carbamoyl-2-phenyl-ethyl) Butyramide</brief_title>
  <official_title>Tolerability and Modulatory Action on Neonatal Gastrointestinal Function and Immunity of the Butyrate Releaser N-(1-carbamoyl-2-phenyl-ethyl) Butyramide as New Component for Infant Formula</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Federico II University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Federico II University</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>
      Accumulating evidence is showing that gut microbiota could play a key role in&#xD;
      gastrointestinal tract and immune system development and function. Many beneficial effects&#xD;
      elicited by gut microbiota are mediated its metabolites. Short chain fatty acids (SCFAs) are&#xD;
      major metabolites produced by gut microbiota. Among SCFA, butyrate has emerged as pivotal&#xD;
      regulator of many gastrointestinal function and immune system development and function.&#xD;
&#xD;
      Butyrate is produced by intestinal microbial fermentation of resistant starches and dietary&#xD;
      fiber. It regulates several beneficial intestinal and extra-intestinal functions, among the&#xD;
      first it serves as the primary energy source for the gut epithelium, increases mineral&#xD;
      absorption, stimulates proliferation and differentiation of normal colon epithelial cells,&#xD;
      improves the gut barrier function by stimulation of the formation of mucin, antimicrobial&#xD;
      peptides, and tight-junction proteins, interacts with the immune system and has&#xD;
      anti-inflammatory effects.&#xD;
&#xD;
      Butyrate also seems to regulate the expression of antimicrobial peptides in particular&#xD;
      upregulating transcription of cathelicidin thanks to his action of histone deacetylase&#xD;
      inhibitor and it has been shown to induce human β-defensin 2 (HBD-2) mRNA expression in&#xD;
      colonocytes, although there are few publications reporting its regulation of defensins (Berni&#xD;
      Canani R et al. W J Gastroenterol. 2011;17(12):1519). Preliminary data showed that breast&#xD;
      milk contains butyrate. Butyrate could be an ideal compound for infant formulas for an&#xD;
      efficient regulation of a number of protective actions at gastrointestinal tract level and at&#xD;
      systemic level.&#xD;
&#xD;
      A new butyrate releaser, useful for all the known applications of butyrate, presenting&#xD;
      physiochemical characteristics suitable for easy oral administration (free from unpleasant&#xD;
      organoleptic properties of butyrate): N-(1-carbamoyl-2-phenyl-ethyl) butyramide (FBA) has&#xD;
      been developed. The molecule is a butyrate amide with the amino acid phenylalanine, solid,&#xD;
      odourless, tasteless, stable at gastric pH, and able to release butyrate constantly&#xD;
      throughout gastrointestinal tract.&#xD;
&#xD;
      The aim of the study was to evaluate tolerability and safety profile of a nutritional&#xD;
      intervention with FBA in formula fed at term neonates. The effects on the expression of&#xD;
      innate immunity biomarkers as well as on neonatal gut function were also assessed.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 9, 2012</start_date>
  <completion_date type="Actual">December 31, 2013</completion_date>
  <primary_completion_date type="Actual">December 31, 2013</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>
    <primary_purpose>Other</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>safety and tolerability: adverse events</measure>
    <time_frame>up to 28 days</time_frame>
    <description>number and proportion of subjects with adverse events</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>percentage of subjects with infantile colics</measure>
    <time_frame>up to 28 days</time_frame>
    <description>rate of subjects with infantile colics</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>daily number of bowel movements</measure>
    <time_frame>up to 28 days</time_frame>
    <description>daily number of bowel movements</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>stool consistency</measure>
    <time_frame>up to 28 days</time_frame>
    <description>stool consistency</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>daily number of regurgitation episodes</measure>
    <time_frame>up to 28 days</time_frame>
    <description>daily number of regurgitation episodes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>fecal levels of of β-defensins 2 (HβD-2)</measure>
    <time_frame>up to 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change of secretory immunoglobulin A (sIgA)</measure>
    <time_frame>up to 28 days</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Safety Issues</condition>
  <arm_group>
    <arm_group_label>FBA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>N-(1-carbamoyl-2-phenyl-ethyl) butyramide (FBA) has been developed.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>maltodextrins</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>FBA</intervention_name>
    <description>N-(1-carbamoyl-2-phenyl-ethyl) butyramide (FBA) has been developed.</description>
    <arm_group_label>FBA</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>maltodextrins</description>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  otherwise healthy formula fed-neonates&#xD;
&#xD;
          -  born at term (&gt;37 gestational age)&#xD;
&#xD;
          -  adequate weight for gestational age&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  twins,&#xD;
&#xD;
          -  infants with history of severe asphyxia,&#xD;
&#xD;
          -  meconium aspiration syndrome,&#xD;
&#xD;
          -  immunodeficiency,&#xD;
&#xD;
          -  congenital infections,&#xD;
&#xD;
          -  genetic diseases and chromosomal abnormalities,&#xD;
&#xD;
          -  malformations,&#xD;
&#xD;
          -  insufficient reliability or presence of conditions that made the patient's compliance&#xD;
             with the protocol unlikely,&#xD;
&#xD;
          -  infants with any other condition which, in the opinion of the Investigator, is likely&#xD;
             to interfere with the ability of the infant to ingest food, or the normal growth and&#xD;
             development of the infant, or the evaluation of the infant.&#xD;
&#xD;
        In addition, as maternal exclusion factors:&#xD;
&#xD;
          -  history of immune diseases,&#xD;
&#xD;
          -  tumors,&#xD;
&#xD;
          -  infectious or inflammatory diseases that required antibiotic therapy during pregnancy,&#xD;
&#xD;
          -  diabetes,&#xD;
&#xD;
          -  gestosis,&#xD;
&#xD;
          -  dyslipidemia,&#xD;
&#xD;
          -  positive vaginal swab for Group B Streptococcus,&#xD;
&#xD;
          -  prolonged rupture of membranes.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>3 Days</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of Naples Federico II</name>
      <address>
        <city>Naples</city>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>July 25, 2020</study_first_submitted>
  <study_first_submitted_qc>July 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 29, 2020</study_first_posted>
  <last_update_submitted>August 11, 2020</last_update_submitted>
  <last_update_submitted_qc>August 11, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 12, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Federico II University</investigator_affiliation>
    <investigator_full_name>Roberto Berni Canani</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04491266
org study id: 20-13
nct id: NCT04491266
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Accumulating evidence is showing that gut microbiota could play a key role in
      gastrointestinal tract and immune system development and function. Many beneficial effects
      elicited by gut microbiota are mediated its metabolites. Short chain fatty acids (SCFAs) are
      major metabolites produced by gut microbiota. Among SCFA, butyrate has emerged as pivotal
      regulator of many gastrointestinal function and immune system development and function.

      Butyrate is produced by intestinal microbial fermentation of resistant starches and dietary
      fiber. It regulates several beneficial intestinal and extra-intestinal functions, among the
      first it serves as the primary energy source for the gut epithelium, increases mineral
      absorption, stimulates proliferation and differentiation of normal colon epithelial cells,
      improves the gut barrier function by stimulation of the formation of mucin, antimicrobial
      peptides, and tight-junction proteins, interacts with the immune system and has
      anti-inflammatory effects.

      Butyrate also seems to regulate the expression of antimicrobial peptides in particular
      upregulating transcription of cathelicidin thanks to his action of histone deacetylase
      inhibitor and it has been shown to induce human β-defensin 2 (HBD-2) mRNA expression in
      colonocytes, although there are few publications reporting its regulation of defensins (Berni
      Canani R et al. W J Gastroenterol. 2011;17(12):1519). Preliminary data showed that breast
      milk contains butyrate. Butyrate could be an ideal compound for infant formulas for an
      efficient regulation of a number of protective actions at gastrointestinal tract level and at
      systemic level.

      A new butyrate releaser, useful for all the known applications of butyrate, presenting
      physiochemical characteristics suitable for easy oral administration (free from unpleasant
      organoleptic properties of butyrate): N-(1-carbamoyl-2-phenyl-ethyl) butyramide (FBA) has
      been developed. The molecule is a butyrate amide with the amino acid phenylalanine, solid,
      odourless, tasteless, stable at gastric pH, and able to release butyrate constantly
      throughout gastrointestinal tract.

      The aim of the study was to evaluate tolerability and safety profile of a nutritional
      intervention with FBA in formula fed at term neonates. The effects on the expression of
      innate immunity biomarkers as well as on neonatal gut function were also assessed.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: safety and tolerability: adverse events
time frame: up to 28 days
description: number and proportion of subjects with adverse events
measure: percentage of subjects with infantile colics
time frame: up to 28 days
description: rate of subjects with infantile colics
measure: daily number of bowel movements
time frame: up to 28 days
description: daily number of bowel movements
measure: stool consistency
time frame: up to 28 days
description: stool consistency
measure: daily number of regurgitation episodes
time frame: up to 28 days
description: daily number of regurgitation episodes
measure: fecal levels of of β-defensins 2 (HβD-2)
time frame: up to 28 days
measure: change of secretory immunoglobulin A (sIgA)
time frame: up to 28 days
arm group label: FBA
arm group type: Experimental
description: N-(1-carbamoyl-2-phenyl-ethyl) butyramide (FBA) has been developed.
arm group label: placebo
arm group type: Placebo Comparator
description: maltodextrins
intervention type: Dietary Supplement
intervention name: FBA
description: N-(1-carbamoyl-2-phenyl-ethyl) butyramide (FBA) has been developed.
arm group label: FBA
intervention type: Dietary Supplement
intervention name: placebo
description: maltodextrins
arm group label: placebo
criteria: 
gender: All
minimum age: N/A
maximum age: 3 Days
healthy volunteers: No
facility: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: Federico II University
investigator full name: Roberto Berni Canani
investigator title: Associate Professor
sharing ipd: Undecided