<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/NCT03272542</url>
  </required_header>
  <id_info>
    <org_study_id>17-22618</org_study_id>
    <secondary_id>R21DK112126</secondary_id>
    <nct_id>NCT03272542</nct_id>
  </id_info>
  <brief_title>PRebiotic to IMprovE Calcium Absorption</brief_title>
  <acronym>PRIME</acronym>
  <official_title>Prebiotic Intervention to Improve Calcium Absorption After Gastric Bypass Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>San Francisco Veterans Affairs Medical Center</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of California, San Francisco</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>San Francisco Veterans Affairs Medical Center</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>
      Gastric bypass surgery is a highly effective treatment for obesity, but it has negative&#xD;
      effects on skeletal health, due in part to a dramatic decline in intestinal calcium&#xD;
      absorption capacity. Animal and human studies suggest that non-digestible fibers termed&#xD;
      prebiotics, such as soluble corn fiber (SCF), augment calcium absorption in the lower&#xD;
      intestine as they act as substrates for beneficial gut microbiota. This is a pilot randomized&#xD;
      controlled trial of the effects of SCF vs. placebo on intestinal calcium absorption, bone&#xD;
      turnover marker levels, and the gut microbiome in postmenopausal women who have previously&#xD;
      undergone gastric bypass surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study is a pilot randomized control trial (RCT) of the effects of the prebiotic SCF vs.&#xD;
      placebo in 20 postmenopausal women who underwent Roux-en-Y gastric bypass surgery 2-6 years&#xD;
      previously and thus have completed the postoperative period of rapid weight loss and&#xD;
      metabolic and dietary change. A 24 g/day dose of SCF85 (which is approximately 20 g/day&#xD;
      fiber) will be tested, as that dose was proven effective for calcium absorption/retention in&#xD;
      healthy postmenopausal women and adolescents. The SCF and the maltodextrin placebo will be&#xD;
      mixed in water and consumed in divided doses twice daily for 2 months, a duration exceeding&#xD;
      other SCF trials but remaining feasible for a pilot. The primary outcome will be change in&#xD;
      intestinal calcium absorption, which is the efficacy outcome about which the study must&#xD;
      collect preliminary data and from which the investigators must refine power calculations for&#xD;
      the anticipated future trial. Because the investigators hypothesize that an increase in&#xD;
      calcium absorption will decrease bone turnover and ultimately increase bone mineral density&#xD;
      (BMD), the study will measure biochemical markers of bone turnover in this pilot. Secondary&#xD;
      outcomes will be gastrointestinal tolerability and acceptability. On an exploratory basis,&#xD;
      the study will determine effects of the prebiotic on the gut microbiome. This pilot will&#xD;
      yield critical experience about feasibility of recruitment and adherence to the intervention&#xD;
      and measurements.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 21, 2017</start_date>
  <completion_date type="Actual">January 31, 2020</completion_date>
  <primary_completion_date type="Actual">January 31, 2020</primary_completion_date>
  <phase>Phase 2</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>Randomized, placebo-controlled pilot trial with a parallel-arm design</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in fractional intestinal calcium absorption</measure>
    <time_frame>2 months</time_frame>
    <description>Fractional calcium absorption to be determined using dual stable isotopic tracers</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in bone turnover markers</measure>
    <time_frame>2 months</time_frame>
    <description>Serum biochemical markers of bone turnover C-telopeptide (CTX) and procollagen type 1 N-terminal propeptide (P1NP)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gastrointestinal tolerability</measure>
    <time_frame>2 months</time_frame>
    <description>Self-reported flatulence, bloating, abdominal pain, stomach noises</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acceptability</measure>
    <time_frame>2 months</time_frame>
    <description>Self-reported satisfaction, likelihood that one would be willing to consume the beverage for 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in gut microbiome composition</measure>
    <time_frame>2 months</time_frame>
    <description>Stool bacterial and fungal composition to be analyzed, including alpha diversity and beta diversity metrics as well as taxon relative abundance, with subsequent in silico metagenomic predictions of enrichment of bacterial functional gene pathways</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Obesity</condition>
  <arm_group>
    <arm_group_label>Prebiotic: soluble corn fiber</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SCF (PromotorTM Soluble Corn Fiber 85, provided by manufacturer Tate &amp; Lyle) will be dispensed to participants as a dry powder in sachets of 12 g SCF85 product (which is approximately 10 g fiber). Participants will mix the powder into 250 mL water and consume two such beverages daily, ≥1 hour apart. (For the first week, all participants will consume one beverage daily, and subsequently increase to one beverage twice daily.) Participants will be asked to substitute these for 500 mL of their usual daily water intake but to make no other dietary changes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The placebo control will be maltodextrin powder in identical sachets. Participants will mix the powder into 250 mL water and consume two such beverages daily, ≥1 hour apart. (For the first week, all participants will consume one beverage daily, and subsequently increase to one beverage twice daily.) Participants will be requested to substitute these for 500 mL of their usual daily water intake but to make no other dietary changes.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Prebiotic: soluble corn fiber</intervention_name>
    <description>prebiotic</description>
    <arm_group_label>Prebiotic: soluble corn fiber</arm_group_label>
    <other_name>PROMOTOR 85</other_name>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo: maltodextrin</intervention_name>
    <description>placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Postmenopausal women (no menses for ≥4 yrs)&#xD;
&#xD;
          2. ≤ 75 yrs old,&#xD;
&#xD;
          3. Underwent Roux-en-Y gastric bypass surgery for weight loss 2-6 years prior&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Serum 25(OH)vitamin D level &lt;30 ng/mL (to remove the effect of vitamin D&#xD;
             insufficiency/deficiency)*&#xD;
&#xD;
          2. History of &gt;1 bariatric surgical procedure&#xD;
&#xD;
          3. Antibiotic therapy in the last 3 months&#xD;
&#xD;
          4. Regular pre- or probiotic use in the last 3 months&#xD;
&#xD;
          5. Regain of &gt;50% of weight loss post-bypass&#xD;
&#xD;
          6. Calculated creatinine clearance &lt;30 mL/min&#xD;
&#xD;
          7. Serum calcium &gt;10.2 mg/dL&#xD;
&#xD;
          8. Use of hormone therapy, osteoporosis pharmacotherapy, glucocorticoids, or other&#xD;
             medications impacting calcium metabolism&#xD;
&#xD;
          9. Thyroid stimulating hormone (TSH) &lt;0.01 milli-international units per liter (mIU/L)&#xD;
&#xD;
        A potential participant may be excluded if she has a condition or abnormality that in the&#xD;
        opinion of the Investigator would compromise the safety of the participant or the quality&#xD;
        of the data.&#xD;
&#xD;
        *Women excluded due to 25(OH)D level will be offered re-screening after vitamin D&#xD;
        supplementation.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anne Schafer, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UCSF &amp; SFVAMC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UCSF</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>August 25, 2017</study_first_submitted>
  <study_first_submitted_qc>September 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 5, 2017</study_first_posted>
  <last_update_submitted>October 20, 2020</last_update_submitted>
  <last_update_submitted_qc>October 20, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>San Francisco Veterans Affairs Medical Center</investigator_affiliation>
    <investigator_full_name>Anne Schafer</investigator_full_name>
    <investigator_title>Assistant Professor of Medicine and of Epidemiology and Biostatistics; Staff Physician</investigator_title>
  </responsible_party>
  <keyword>gastric bypass</keyword>
  <keyword>calcium absorption</keyword>
  <keyword>postmenopausal women</keyword>
  <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/NCT03272542
org study id: 17-22618
secondary id: R21DK112126
nct id: NCT03272542
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Gastric bypass surgery is a highly effective treatment for obesity, but it has negative
      effects on skeletal health, due in part to a dramatic decline in intestinal calcium
      absorption capacity. Animal and human studies suggest that non-digestible fibers termed
      prebiotics, such as soluble corn fiber (SCF), augment calcium absorption in the lower
      intestine as they act as substrates for beneficial gut microbiota. This is a pilot randomized
      controlled trial of the effects of SCF vs. placebo on intestinal calcium absorption, bone
      turnover marker levels, and the gut microbiome in postmenopausal women who have previously
      undergone gastric bypass surgery.
The study is a pilot randomized control trial (RCT) of the effects of the prebiotic SCF vs.
      placebo in 20 postmenopausal women who underwent Roux-en-Y gastric bypass surgery 2-6 years
      previously and thus have completed the postoperative period of rapid weight loss and
      metabolic and dietary change. A 24 g/day dose of SCF85 (which is approximately 20 g/day
      fiber) will be tested, as that dose was proven effective for calcium absorption/retention in
      healthy postmenopausal women and adolescents. The SCF and the maltodextrin placebo will be
      mixed in water and consumed in divided doses twice daily for 2 months, a duration exceeding
      other SCF trials but remaining feasible for a pilot. The primary outcome will be change in
      intestinal calcium absorption, which is the efficacy outcome about which the study must
      collect preliminary data and from which the investigators must refine power calculations for
      the anticipated future trial. Because the investigators hypothesize that an increase in
      calcium absorption will decrease bone turnover and ultimately increase bone mineral density
      (BMD), the study will measure biochemical markers of bone turnover in this pilot. Secondary
      outcomes will be gastrointestinal tolerability and acceptability. On an exploratory basis,
      the study will determine effects of the prebiotic on the gut microbiome. This pilot will
      yield critical experience about feasibility of recruitment and adherence to the intervention
      and measurements.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized, placebo-controlled pilot trial with a parallel-arm design
primary purpose: Other
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in fractional intestinal calcium absorption
time frame: 2 months
description: Fractional calcium absorption to be determined using dual stable isotopic tracers
measure: Change in bone turnover markers
time frame: 2 months
description: Serum biochemical markers of bone turnover C-telopeptide (CTX) and procollagen type 1 N-terminal propeptide (P1NP)
measure: Gastrointestinal tolerability
time frame: 2 months
description: Self-reported flatulence, bloating, abdominal pain, stomach noises
measure: Acceptability
time frame: 2 months
description: Self-reported satisfaction, likelihood that one would be willing to consume the beverage for 12 months
measure: Change in gut microbiome composition
time frame: 2 months
description: Stool bacterial and fungal composition to be analyzed, including alpha diversity and beta diversity metrics as well as taxon relative abundance, with subsequent in silico metagenomic predictions of enrichment of bacterial functional gene pathways
arm group label: Prebiotic: soluble corn fiber
arm group type: Experimental
description: SCF (PromotorTM Soluble Corn Fiber 85, provided by manufacturer Tate & Lyle) will be dispensed to participants as a dry powder in sachets of 12 g SCF85 product (which is approximately 10 g fiber). Participants will mix the powder into 250 mL water and consume two such beverages daily, ≥1 hour apart. (For the first week, all participants will consume one beverage daily, and subsequently increase to one beverage twice daily.) Participants will be asked to substitute these for 500 mL of their usual daily water intake but to make no other dietary changes.
arm group label: Placebo
arm group type: Placebo Comparator
description: The placebo control will be maltodextrin powder in identical sachets. Participants will mix the powder into 250 mL water and consume two such beverages daily, ≥1 hour apart. (For the first week, all participants will consume one beverage daily, and subsequently increase to one beverage twice daily.) Participants will be requested to substitute these for 500 mL of their usual daily water intake but to make no other dietary changes.
intervention type: Dietary Supplement
intervention name: Prebiotic: soluble corn fiber
description: prebiotic
arm group label: Prebiotic: soluble corn fiber
other name: PROMOTOR 85
intervention type: Dietary Supplement
intervention name: Placebo: maltodextrin
description: placebo
arm group label: Placebo
criteria: 
gender: Female
gender based: Yes
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Anne Schafer, MD
role: Principal Investigator
affiliation: UCSF & SFVAMC
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: San Francisco Veterans Affairs Medical Center
investigator full name: Anne Schafer
investigator title: Assistant Professor of Medicine and of Epidemiology and Biostatistics; Staff Physician
sharing ipd: No