<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/NCT03269617</url>
  </required_header>
  <id_info>
    <org_study_id>16-6666HH</org_study_id>
    <nct_id>NCT03269617</nct_id>
  </id_info>
  <brief_title>PHAGE Study: Bacteriophages as Novel Prebiotics</brief_title>
  <official_title>PreforPro: A Randomized, Placebo Controlled Crossover Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Colorado State University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>George Mason University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Metabiomics Corp</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Colorado State 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>
      The PHAGE study is designed to determine if a commercial prebiotic product can change the&#xD;
      composition of bacteria in the gut for improved intestinal health. A prebiotic is defined as&#xD;
      an indigestible dietary component that selectively enhances specific bacterial species in the&#xD;
      intestines to confer a health benefit. In this study, the prebiotic a unique combination of&#xD;
      bacteriophages, or viruses that infect bacteria. These phages are generally regarded as safe&#xD;
      for human consumption and work by infecting bad bacteria in the gut, which allows beneficial&#xD;
      bacteria populations to increase. The product, PreforPro, has shown to be effective in&#xD;
      culture-based and animal studies, but its efficacy has not been demonstrated in humans. The&#xD;
      goal of this study is to see if PreforPro consumption improves gut bacteria profiles in&#xD;
      individuals relative to a placebo control and is associated with reduced incidence and&#xD;
      severity of gastrointestinal distress.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The goal of this study is to see if consumption of PreforPro, a commercially available&#xD;
      prebiotic dietary supplement consisting of a mixture of bacteriophages, improves gut bacteria&#xD;
      profiles in individuals relative to a placebo control. Secondary outcome measures include&#xD;
      determining changes in comprehensive metabolic profiles, inflammatory markers (systemic and&#xD;
      local), microbial metabolites, and perceptions of gastrointestinal distress. To accomplish&#xD;
      these research goals, 40 male and female volunteers between 18-65 years old with BMI scores&#xD;
      of 20 to 34.9 who suffer from mild gastrointestinal distress will be enrolled.Recruitment&#xD;
      will be by referral from local practitioners and through email solicitations. Eligibility&#xD;
      will be determined at the Colorado State University Medical Nutrition Therapy Laboratory&#xD;
      (MNTL) by a screening questionnaire and interview/assessment by the clinical coordinator.&#xD;
      After determining eligibility and securing consent, participants will randomly be assigned to&#xD;
      1 of 2 treatment groups: prebiotic or placebo. Participants will consume one capsule daily of&#xD;
      respective treatments for a period of four (4) weeks. At the beginning and end of the 4 week&#xD;
      treatment periods blood and stool samples will be collected at the Human Performance Clinical&#xD;
      Research Laboratory (HPCRL). This means that participants will make a total of four (4)&#xD;
      clinic visits during each treatment period. Following the initial treatment period, all&#xD;
      participants will be required to undergo a wash-out period for two (2) weeks. Upon completion&#xD;
      of the wash-out period, participants will switch treatment groups for a period of four (4)&#xD;
      weeks. Clinic visits at baseline and 4-weeks for collection of stool and blood samples will&#xD;
      also be conducted during the second treatment period. Study participants will be required to&#xD;
      provide a total of four (4) fecal samples and four (4) fasting blood samples. Additionally,&#xD;
      study participants will be required to provide a weekly assessment of GI symptoms during the&#xD;
      two treatment periods. All blood samples will be collected at Colorado State University by&#xD;
      trained professionals. Fecal sample collection will be performed by the study participant&#xD;
      with collection materials provided by study personnel. Both participants and researchers will&#xD;
      be blinded during the course of the intervention and throughout the data analysis period.&#xD;
      Blinding will be conducted by individuals from Deerland Enzymes, the company that is&#xD;
      providing the capsules for intervention.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 1, 2016</start_date>
  <completion_date type="Actual">May 30, 2017</completion_date>
  <primary_completion_date type="Actual">May 30, 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>
    <intervention_model_description>The PHAGE Study is a randomized, double-blind, placebo controlled crossover trial that investigates the utility of four supplemental bacteriophage strains (LH01-Myoviridae, LL5-Siphoviridae, T4D-Myoviridae, and LL12-Myoviridae) to modulate the gut microbiota, and therefore ameliorate common inflammation-related GI distress symptoms (e.g., gas, bloating, diarrhea, constipation, etc) experienced by healthy individuals.</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    <masking_description>Samples were provided in coded bottles whose identity is known only to the product manufacturer. Blinding will persist until all samples have been processed and the data statistically analyzed.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Microbiota modulation</measure>
    <time_frame>Baseline visit prior to starting treatments,4 weeks after starting treatment 1, end of 2-week washout period, 4-weeks after starting treatment 2</time_frame>
    <description>Use of 16s rRNA sequencing of stool samples to determine whether the administered interventions resulted in changes to microbial composition.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Local inflammation</measure>
    <time_frame>Baseline visit prior to starting treatments,4 weeks after starting treatment 1, end of 2-week washout period, 4-weeks after starting treatment 2</time_frame>
    <description>Inflammation in the bowels will be assessed by use of ELISA test for fecal calprotectin.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Systemic Inflammation</measure>
    <time_frame>Baseline visit prior to starting treatments,4 weeks after starting treatment 1, end of 2-week washout period, 4-weeks after starting treatment 2</time_frame>
    <description>Systemic inflammation will be assessed by an ELISA test for CRP and circulating cytokines and immune factors.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Microbial metabolism</measure>
    <time_frame>Baseline visit prior to starting treatments,4 weeks after starting treatment 1, end of 2-week washout period, 4-weeks after starting treatment 2</time_frame>
    <description>Fermentation by microbes in the gut will be assessed by measuring fecal short chain fatty acid concentrations.</description>
  </other_outcome>
  <other_outcome>
    <measure>Circulating lipids</measure>
    <time_frame>Baseline visit prior to starting treatments,4 weeks after starting treatment 1, end of 2-week washout period, 4-weeks after starting treatment 2</time_frame>
    <description>Total cholesterol, LDL, HDL, and triglycerides will be determined in venous blood using a clinical analyzer (Piccolo Xpress).</description>
  </other_outcome>
  <other_outcome>
    <measure>Comprehensive metabolic panel</measure>
    <time_frame>Baseline visit prior to starting treatments,4 weeks after starting treatment 1, end of 2-week washout period, 4-weeks after starting treatment 2</time_frame>
    <description>Basic metabolic parameters such as fasting glucose, and levels of BUN, creatinine, and liver enzymes will be determined from a single 200 ul aliquot of venous blood using a CMP clinical analysis panel for Piccolo Xpress.</description>
  </other_outcome>
  <other_outcome>
    <measure>GI symptom self-assessment</measure>
    <time_frame>Baseline visit prior to starting treatments,4 weeks after starting treatment 1, end of 2-week washout period, 4-weeks after starting treatment 2</time_frame>
    <description>Participants will complete a validated questionnaire to track changes in GI symptoms.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">43</enrollment>
  <condition>Gastrointestinal Disorder, Functional</condition>
  <arm_group>
    <arm_group_label>Placebo Comparator</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo control: 1 capsule containing rice maltodextrin consumed 1x daily for 28 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Experimental</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Bacteriophage mixture: 1 capsule containing rice maltodextrin and a mixture of 4 bacteriophages consumed 1x daily for 28 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Bacteriophage mixture</intervention_name>
    <description>Four bacteriophage strains: LH01-Myoviridae, LL5-Siphoviridae, T4D-Myoviridae, and LL12-Myoviridae.</description>
    <arm_group_label>Experimental</arm_group_label>
    <other_name>PreforPro</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo Control</intervention_name>
    <description>Placebo control capsule consisting of rice maltodextrin</description>
    <arm_group_label>Placebo Comparator</arm_group_label>
    <other_name>rice maltodextrin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy adults&#xD;
&#xD;
          -  18-65 years old&#xD;
&#xD;
          -  Mild to moderate GI distress (self-assessed)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or breastfeeding&#xD;
&#xD;
          -  Diagnosed GI disease (Celiac, peptic ulcer, ulcerative colitis, Crohn's disease,&#xD;
             cancer, or other gastrointestinal or metabolic diseases)&#xD;
&#xD;
          -  Antibiotic use in the past 2 months&#xD;
&#xD;
          -  Use of NSAIDS, statins, metformin, and other drugs known to modify the gut microbiota&#xD;
&#xD;
          -  BMI less than 18.0 or greater than 35.0&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tiffany Weir, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Colorado State University</affiliation>
  </overall_official>
  <results_reference>
    <citation>Febvre HP, Rao S, Gindin M, Goodwin NDM, Finer E, Vivanco JS, Lu S, Manter DK, Wallace TC, Weir TL. PHAGE Study: Effects of Supplemental Bacteriophage Intake on Inflammation and Gut Microbiota in Healthy Adults. Nutrients. 2019 Mar 20;11(3):666. doi: 10.3390/nu11030666.</citation>
    <PMID>30897686</PMID>
  </results_reference>
  <results_reference>
    <citation>Gindin M, Febvre HP, Rao S, Wallace TC, Weir TL. Bacteriophage for Gastrointestinal Health (PHAGE) Study: Evaluating the Safety and Tolerability of Supplemental Bacteriophage Consumption. J Am Coll Nutr. 2019 Jan;38(1):68-75. doi: 10.1080/07315724.2018.1483783. Epub 2018 Aug 29.</citation>
    <PMID>30157383</PMID>
  </results_reference>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>August 1, 2017</study_first_submitted>
  <study_first_submitted_qc>August 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 1, 2017</study_first_posted>
  <last_update_submitted>April 2, 2019</last_update_submitted>
  <last_update_submitted_qc>April 2, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 4, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Colorado State University</investigator_affiliation>
    <investigator_full_name>Tiffany Weir</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>dysbiosis</keyword>
  <keyword>gut microbiota</keyword>
  <keyword>bacteriophage</keyword>
  <keyword>irritable bowel syndrome</keyword>
  <keyword>gastrointestinal distress</keyword>
  <keyword>prebiotic</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gastrointestinal Diseases</mesh_term>
    <mesh_term>Digestive System Diseases</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/NCT03269617
org study id: 16-6666HH
nct id: NCT03269617
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The PHAGE study is designed to determine if a commercial prebiotic product can change the
      composition of bacteria in the gut for improved intestinal health. A prebiotic is defined as
      an indigestible dietary component that selectively enhances specific bacterial species in the
      intestines to confer a health benefit. In this study, the prebiotic a unique combination of
      bacteriophages, or viruses that infect bacteria. These phages are generally regarded as safe
      for human consumption and work by infecting bad bacteria in the gut, which allows beneficial
      bacteria populations to increase. The product, PreforPro, has shown to be effective in
      culture-based and animal studies, but its efficacy has not been demonstrated in humans. The
      goal of this study is to see if PreforPro consumption improves gut bacteria profiles in
      individuals relative to a placebo control and is associated with reduced incidence and
      severity of gastrointestinal distress.
The goal of this study is to see if consumption of PreforPro, a commercially available
      prebiotic dietary supplement consisting of a mixture of bacteriophages, improves gut bacteria
      profiles in individuals relative to a placebo control. Secondary outcome measures include
      determining changes in comprehensive metabolic profiles, inflammatory markers (systemic and
      local), microbial metabolites, and perceptions of gastrointestinal distress. To accomplish
      these research goals, 40 male and female volunteers between 18-65 years old with BMI scores
      of 20 to 34.9 who suffer from mild gastrointestinal distress will be enrolled.Recruitment
      will be by referral from local practitioners and through email solicitations. Eligibility
      will be determined at the Colorado State University Medical Nutrition Therapy Laboratory
      (MNTL) by a screening questionnaire and interview/assessment by the clinical coordinator.
      After determining eligibility and securing consent, participants will randomly be assigned to
      1 of 2 treatment groups: prebiotic or placebo. Participants will consume one capsule daily of
      respective treatments for a period of four (4) weeks. At the beginning and end of the 4 week
      treatment periods blood and stool samples will be collected at the Human Performance Clinical
      Research Laboratory (HPCRL). This means that participants will make a total of four (4)
      clinic visits during each treatment period. Following the initial treatment period, all
      participants will be required to undergo a wash-out period for two (2) weeks. Upon completion
      of the wash-out period, participants will switch treatment groups for a period of four (4)
      weeks. Clinic visits at baseline and 4-weeks for collection of stool and blood samples will
      also be conducted during the second treatment period. Study participants will be required to
      provide a total of four (4) fecal samples and four (4) fasting blood samples. Additionally,
      study participants will be required to provide a weekly assessment of GI symptoms during the
      two treatment periods. All blood samples will be collected at Colorado State University by
      trained professionals. Fecal sample collection will be performed by the study participant
      with collection materials provided by study personnel. Both participants and researchers will
      be blinded during the course of the intervention and throughout the data analysis period.
      Blinding will be conducted by individuals from Deerland Enzymes, the company that is
      providing the capsules for intervention.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: The PHAGE Study is a randomized, double-blind, placebo controlled crossover trial that investigates the utility of four supplemental bacteriophage strains (LH01-Myoviridae, LL5-Siphoviridae, T4D-Myoviridae, and LL12-Myoviridae) to modulate the gut microbiota, and therefore ameliorate common inflammation-related GI distress symptoms (e.g., gas, bloating, diarrhea, constipation, etc) experienced by healthy individuals.
primary purpose: Basic Science
masking: Triple (Participant, Investigator, Outcomes Assessor)
masking description: Samples were provided in coded bottles whose identity is known only to the product manufacturer. Blinding will persist until all samples have been processed and the data statistically analyzed.
measure: Microbiota modulation
time frame: Baseline visit prior to starting treatments,4 weeks after starting treatment 1, end of 2-week washout period, 4-weeks after starting treatment 2
description: Use of 16s rRNA sequencing of stool samples to determine whether the administered interventions resulted in changes to microbial composition.
measure: Local inflammation
time frame: Baseline visit prior to starting treatments,4 weeks after starting treatment 1, end of 2-week washout period, 4-weeks after starting treatment 2
description: Inflammation in the bowels will be assessed by use of ELISA test for fecal calprotectin.
measure: Systemic Inflammation
time frame: Baseline visit prior to starting treatments,4 weeks after starting treatment 1, end of 2-week washout period, 4-weeks after starting treatment 2
description: Systemic inflammation will be assessed by an ELISA test for CRP and circulating cytokines and immune factors.
measure: Microbial metabolism
time frame: Baseline visit prior to starting treatments,4 weeks after starting treatment 1, end of 2-week washout period, 4-weeks after starting treatment 2
description: Fermentation by microbes in the gut will be assessed by measuring fecal short chain fatty acid concentrations.
measure: Circulating lipids
time frame: Baseline visit prior to starting treatments,4 weeks after starting treatment 1, end of 2-week washout period, 4-weeks after starting treatment 2
description: Total cholesterol, LDL, HDL, and triglycerides will be determined in venous blood using a clinical analyzer (Piccolo Xpress).
measure: Comprehensive metabolic panel
time frame: Baseline visit prior to starting treatments,4 weeks after starting treatment 1, end of 2-week washout period, 4-weeks after starting treatment 2
description: Basic metabolic parameters such as fasting glucose, and levels of BUN, creatinine, and liver enzymes will be determined from a single 200 ul aliquot of venous blood using a CMP clinical analysis panel for Piccolo Xpress.
measure: GI symptom self-assessment
time frame: Baseline visit prior to starting treatments,4 weeks after starting treatment 1, end of 2-week washout period, 4-weeks after starting treatment 2
description: Participants will complete a validated questionnaire to track changes in GI symptoms.
arm group label: Placebo Comparator
arm group type: Placebo Comparator
description: Placebo control: 1 capsule containing rice maltodextrin consumed 1x daily for 28 days.
arm group label: Experimental
arm group type: Experimental
description: Bacteriophage mixture: 1 capsule containing rice maltodextrin and a mixture of 4 bacteriophages consumed 1x daily for 28 days.
intervention type: Dietary Supplement
intervention name: Bacteriophage mixture
description: Four bacteriophage strains: LH01-Myoviridae, LL5-Siphoviridae, T4D-Myoviridae, and LL12-Myoviridae.
arm group label: Experimental
other name: PreforPro
intervention type: Other
intervention name: Placebo Control
description: Placebo control capsule consisting of rice maltodextrin
arm group label: Placebo Comparator
other name: rice maltodextrin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Tiffany Weir, PhD
role: Principal Investigator
affiliation: Colorado State University
citation: Febvre HP, Rao S, Gindin M, Goodwin NDM, Finer E, Vivanco JS, Lu S, Manter DK, Wallace TC, Weir TL. PHAGE Study: Effects of Supplemental Bacteriophage Intake on Inflammation and Gut Microbiota in Healthy Adults. Nutrients. 2019 Mar 20;11(3):666. doi: 10.3390/nu11030666.
PMID: 30897686
citation: Gindin M, Febvre HP, Rao S, Wallace TC, Weir TL. Bacteriophage for Gastrointestinal Health (PHAGE) Study: Evaluating the Safety and Tolerability of Supplemental Bacteriophage Consumption. J Am Coll Nutr. 2019 Jan;38(1):68-75. doi: 10.1080/07315724.2018.1483783. Epub 2018 Aug 29.
PMID: 30157383
responsible party type: Principal Investigator
investigator affiliation: Colorado State University
investigator full name: Tiffany Weir
investigator title: Associate Professor
mesh term: Gastrointestinal Diseases
mesh term: Digestive System Diseases
sharing ipd: No