<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/NCT04431960</url>
  </required_header>
  <id_info>
    <org_study_id>HR20-0035</org_study_id>
    <secondary_id>2020-67018-30852</secondary_id>
    <nct_id>NCT04431960</nct_id>
  </id_info>
  <brief_title>Blackcurrants Modify Gut Microbiota and Reduce Osteoporosis and CVD Risk</brief_title>
  <official_title>Blackcurrant Modifies Gut Microbiota and Reduces the Risk of Postmenopausal Osteoporosis and Cardiovascular Disease: A Pilot Randomized Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Connecticut</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Connecticut</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</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>
      Aim to evaluate the effects of blackcurrant supplementation on changes in gut microbiome,&#xD;
      bone mass, and CVD risk factors in adult women.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Postmenopausal bone loss is a primary contributor to osteoporosis and osteoporotic fractures&#xD;
      in adult women in menopause transition. By following women over this period, studies have&#xD;
      documented distinct patterns of a decrease in estrogen, a natural antioxidant, simultaneously&#xD;
      with adverse alterations in body fat distribution, lipids and lipoproteins, and measures of&#xD;
      vascular health, which can increase a woman's risk of developing CVD. Overall goal of this&#xD;
      project is to evaluate the effects of blackcurrant (BC) supplementation on changes in gut&#xD;
      microbiome, bone mass, and CVD risk factors in adult women. For this purpose, the&#xD;
      investigators will conduct a pilot randomized placebo-controlled clinical trial with BC&#xD;
      supplementation for 6 months in peri- and early postmenopausal women aged 45-60 years.&#xD;
&#xD;
      The primary endpoint will be whole-body bone mineral density (BMD); secondary endpoints will&#xD;
      be gut microbiota composition. To delineate the underlying mechanisms of the action, changes&#xD;
      in biomarkers for bone metabolism, bone-related immune and endocrine systemic biomarkers, and&#xD;
      CVD risk factors by BC supplementation will be measured in plasma and peripheral blood&#xD;
      derived mononuclear cells.&#xD;
&#xD;
      The specific objectives of the study are to investigate the effects of BC extract on: 1) bone&#xD;
      mass and bone remodeling markers; 2) changes in the gut microbiota abundance and composition,&#xD;
      immune and endocrine biomarkers, and CVD risk factors and their relationships with changes in&#xD;
      bone mass.&#xD;
&#xD;
      The proposed study will provide novel insight into whether and how BC consumption reduces the&#xD;
      risk of postmenopausal bone loss and CVD in adult women and will improve understanding of the&#xD;
      clinical roles of gut microbiome in postmenopausal bone loss. Findings from this study will&#xD;
      help increase awareness of the bone and heart health promoting effect of BC and motivate&#xD;
      increased production of BC and other berry products in response to the increasing consumer&#xD;
      demand.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 20, 2021</start_date>
  <completion_date type="Actual">October 3, 2022</completion_date>
  <primary_completion_date type="Actual">October 3, 2022</primary_completion_date>
  <phase>Phase 1</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>The study participants will be randomly assigned to three groups and asked to consume 1 tablet containing 392 mg blackcurrant (BC) extract per capsule (low-BC Group), 2 capsules containing 392 mg BC extract per tablet (total 784 mg/day; high-BC Group), or 1 placebo capsule (Control Group) daily with breakfast meals for 6 months.&#xD;
To avoid bone deterioration related to calcium and vitamin D deficiency, all participants will take a calcium citrate caplet daily that includes 400 mg calcium and 500 IU vitamin D (Bayer AG, Germany) beginning 2 weeks before the study and lasting for the duration of the study.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>The extract and placebo will have the identical shape and color and will be packaged into coded containers.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Bone mineral density (BMD)</measure>
    <time_frame>from baseline to 6 months</time_frame>
    <description>changes in BMD of whole-body, head, arms, legs, trunk, ribs, spine, pelvis</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Gut microbiota profile</measure>
    <time_frame>from baseline to 6 months</time_frame>
    <description>changes in the gut microbial composition</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Serum bone metabolism biomarkers</measure>
    <time_frame>from baseline to 6 months</time_frame>
    <description>changes in serum concentrations of bone metabolism (BALP, P1NP, CTX-1, OC)</description>
  </other_outcome>
  <other_outcome>
    <measure>Serum inflammation biomarker</measure>
    <time_frame>from baseline to 6 months</time_frame>
    <description>changes in serum inflammation biomarker (hs-CRP)</description>
  </other_outcome>
  <other_outcome>
    <measure>Plasma CVD risk factors (lipids, oxidative stress, endothelial function)</measure>
    <time_frame>from baseline to 6 months</time_frame>
    <description>changes in plasma CVD risk factors</description>
  </other_outcome>
  <other_outcome>
    <measure>Blood pressure (SBP/DBP), BMI, WC, body composition</measure>
    <time_frame>from baseline to 6 months</time_frame>
    <description>changes in blood pressure (SBP/DBP), BMI, WC, body composition</description>
  </other_outcome>
  <other_outcome>
    <measure>Concentrations of plasma IL-1β, IL-6, TNFα, Th17 and Treg</measure>
    <time_frame>from baseline to 6 months</time_frame>
    <description>changes in plasma concentrations of immune biomarkers</description>
  </other_outcome>
  <other_outcome>
    <measure>Concentrations of plasma IGF-1 and cGP</measure>
    <time_frame>from baseline to 6 months</time_frame>
    <description>changes in plasma concentrations of endocrine biomarkers</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">54</enrollment>
  <condition>Postmenopausal Osteoporosis</condition>
  <condition>Gut Microbiota</condition>
  <condition>Cardiovascular Diseases</condition>
  <arm_group>
    <arm_group_label>low-BC Group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>consume: 1) one tablet containing 392 mg blackcurrant (BC) extract per capsule and 2) one calcium citrate caplet containing 400 mg calcium and 500 IU vitamin D</description>
  </arm_group>
  <arm_group>
    <arm_group_label>high-BC Group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>consume: 1) two capsules containing 392 mg BC extract per tablet (total 784 mg/day) and 2) one calcium citrate caplet containing 400 mg calcium and 500 IU vitamin D</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>consume: 1) one placebo capsule and 2) one calcium citrate caplet containing 400 mg calcium and 500 IU vitamin D</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>blackcurrant (BC) extract</intervention_name>
    <description>A calcium citrate caplet (Bayer AG, Germany) will be taken by all 3 groups to avoid bone deterioration related to calcium and vitamin D deficiency</description>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_label>high-BC Group</arm_group_label>
    <arm_group_label>low-BC Group</arm_group_label>
    <other_name>BPE75 (392 mg and 784 mg)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  perimenopausal or early postmenopausal women aged 45-60 years old&#xD;
&#xD;
          -  not on HRT for at least one year before the initiation of the study&#xD;
&#xD;
          -  maintaining normal exercise level (&lt;7 h/wk) and willing to avoid exercise 24-h prior&#xD;
             to blood and stool sampling and 12-h prior to bone measurements&#xD;
&#xD;
          -  willing to ingest a dietary BC supplement or placebo (up to 900 mg/day, two 450 mg&#xD;
             capsules) as well as 400 mg calcium and 500 IU vitamin D daily&#xD;
&#xD;
          -  willing to avoid other dietary supplements for the duration of the study&#xD;
&#xD;
          -  willing to avoid intake of foods extremely rich in anthocyanins and fermented dairy&#xD;
             products containing viable Bifidobacteria or Lactobacilli&#xD;
&#xD;
          -  willing to have 3 blood draws, 2 stool collections, and 2 bone scans&#xD;
&#xD;
          -  willing to take urine pregnancy test if they are perimenopausal.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  those with metabolic bone disease, renal disease, cancer, cardiovascular disease,&#xD;
             diabetes mellitus, respiratory disease, gastrointestinal disease, liver disease or&#xD;
             other chronic diseases&#xD;
&#xD;
          -  those with hypertension or on drugs that lower blood pressure&#xD;
&#xD;
          -  those with planned surgery during the study period or within 2 weeks of ending the&#xD;
             intervention&#xD;
&#xD;
          -  taking medications that alter bleeding (such as antiplatelets or anticoagulants) or&#xD;
             those with a bleeding disorder&#xD;
&#xD;
          -  taking a phenothiazine drug (most commonly used for nausea or mental health&#xD;
             conditions)&#xD;
&#xD;
          -  having a sensitivity or allergy to any of ingredients for the placebo (rice powder)&#xD;
             and calcium/D supplement (calcium citrate, polyethylene glycol, croscarmellose sodium,&#xD;
             hydroxypropyl methylcellulose, magnesium stearate, oligofructose enriched inulin,&#xD;
             propylene glycol dicaprylate/dicaprate, talc, titanium dioxide, vitamin D3)&#xD;
&#xD;
          -  heavy smokers (&gt;20 cigarettes/day)&#xD;
&#xD;
          -  perimenopausal women with any chance or plan of pregnancy&#xD;
&#xD;
          -  taking prescription medications known to alter bone and Ca metabolism such as&#xD;
             calcitonin, bisphosphonates, raloxifene within 3 months before the start of the study&#xD;
&#xD;
          -  taking anabolic agents such as parathyroid hormone, growth hormone, or steroids within&#xD;
             3 months before the start of the study&#xD;
&#xD;
          -  planning any procedure that includes iodine, barium or nuclear medicine isotopes in&#xD;
             next 7 months&#xD;
&#xD;
          -  alcohol consumption exceeding 2 drinks/day (approximately 14 g ethanol per drink) or a&#xD;
             total of 12/week&#xD;
&#xD;
          -  UConn students and/or employees who any key personnel teach or who report to any key&#xD;
             personnel&#xD;
&#xD;
          -  study key personnel, spouses of key personnel, or dependents/relatives of any key&#xD;
             personnel.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>perimenopausal or early postmenopausal women</gender_description>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ock K Chun, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Connecticut</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Connecticut Department of Nutritional Sciences and Kinesiology Human Performance Laboratory</name>
      <address>
        <city>Storrs</city>
        <state>Connecticut</state>
        <zip>06269</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>June 6, 2020</study_first_submitted>
  <study_first_submitted_qc>June 11, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>December 1, 2022</last_update_submitted>
  <last_update_submitted_qc>December 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 5, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Connecticut</investigator_affiliation>
    <investigator_full_name>Ock Chun</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>blackcurrant</keyword>
  <keyword>gut microbiome</keyword>
  <keyword>osteoporosis</keyword>
  <keyword>menopause</keyword>
  <keyword>bone aging</keyword>
  <keyword>women</keyword>
  <keyword>cardiovascular disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoporosis</mesh_term>
    <mesh_term>Osteoporosis, Postmenopausal</mesh_term>
    <mesh_term>Cardiovascular Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Once research proceedings and manuscripts are published we will make our results available both to the community of scientists interested in postmenopausal osteoporosis and to those studying the biology of inflammation-induced bone resorption to avoid unintentional duplication of research.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Unlimited time after papers are published.</ipd_time_frame>
    <ipd_access_criteria>Our plan of sharing of data generated by this project includes the following:&#xD;
Presentations at national scientific meetings. From the projects, it is expected that approximately two presentations at national meetings would be appropriate.&#xD;
Publication in peer-reviewed journals. It is our explicit intention that the study findings and key data will be placed in a readily accessible public database. All efforts will be made to rapidly release data through publication of results as quickly as possible following our analysis of the experiment data. Data used in publications will be released in a timely manner.</ipd_access_criteria>
  </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/NCT04431960
org study id: HR20-0035
secondary id: 2020-67018-30852
nct id: NCT04431960
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Aim to evaluate the effects of blackcurrant supplementation on changes in gut microbiome,
      bone mass, and CVD risk factors in adult women.
Postmenopausal bone loss is a primary contributor to osteoporosis and osteoporotic fractures
      in adult women in menopause transition. By following women over this period, studies have
      documented distinct patterns of a decrease in estrogen, a natural antioxidant, simultaneously
      with adverse alterations in body fat distribution, lipids and lipoproteins, and measures of
      vascular health, which can increase a woman's risk of developing CVD. Overall goal of this
      project is to evaluate the effects of blackcurrant (BC) supplementation on changes in gut
      microbiome, bone mass, and CVD risk factors in adult women. For this purpose, the
      investigators will conduct a pilot randomized placebo-controlled clinical trial with BC
      supplementation for 6 months in peri- and early postmenopausal women aged 45-60 years.

      The primary endpoint will be whole-body bone mineral density (BMD); secondary endpoints will
      be gut microbiota composition. To delineate the underlying mechanisms of the action, changes
      in biomarkers for bone metabolism, bone-related immune and endocrine systemic biomarkers, and
      CVD risk factors by BC supplementation will be measured in plasma and peripheral blood
      derived mononuclear cells.

      The specific objectives of the study are to investigate the effects of BC extract on: 1) bone
      mass and bone remodeling markers; 2) changes in the gut microbiota abundance and composition,
      immune and endocrine biomarkers, and CVD risk factors and their relationships with changes in
      bone mass.

      The proposed study will provide novel insight into whether and how BC consumption reduces the
      risk of postmenopausal bone loss and CVD in adult women and will improve understanding of the
      clinical roles of gut microbiome in postmenopausal bone loss. Findings from this study will
      help increase awareness of the bone and heart health promoting effect of BC and motivate
      increased production of BC and other berry products in response to the increasing consumer
      demand.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: The study participants will be randomly assigned to three groups and asked to consume 1 tablet containing 392 mg blackcurrant (BC) extract per capsule (low-BC Group), 2 capsules containing 392 mg BC extract per tablet (total 784 mg/day; high-BC Group), or 1 placebo capsule (Control Group) daily with breakfast meals for 6 months.
To avoid bone deterioration related to calcium and vitamin D deficiency, all participants will take a calcium citrate caplet daily that includes 400 mg calcium and 500 IU vitamin D (Bayer AG, Germany) beginning 2 weeks before the study and lasting for the duration of the study.
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: The extract and placebo will have the identical shape and color and will be packaged into coded containers.
measure: Bone mineral density (BMD)
time frame: from baseline to 6 months
description: changes in BMD of whole-body, head, arms, legs, trunk, ribs, spine, pelvis
measure: Gut microbiota profile
time frame: from baseline to 6 months
description: changes in the gut microbial composition
measure: Serum bone metabolism biomarkers
time frame: from baseline to 6 months
description: changes in serum concentrations of bone metabolism (BALP, P1NP, CTX-1, OC)
measure: Serum inflammation biomarker
time frame: from baseline to 6 months
description: changes in serum inflammation biomarker (hs-CRP)
measure: Plasma CVD risk factors (lipids, oxidative stress, endothelial function)
time frame: from baseline to 6 months
description: changes in plasma CVD risk factors
measure: Blood pressure (SBP/DBP), BMI, WC, body composition
time frame: from baseline to 6 months
description: changes in blood pressure (SBP/DBP), BMI, WC, body composition
measure: Concentrations of plasma IL-1β, IL-6, TNFα, Th17 and Treg
time frame: from baseline to 6 months
description: changes in plasma concentrations of immune biomarkers
measure: Concentrations of plasma IGF-1 and cGP
time frame: from baseline to 6 months
description: changes in plasma concentrations of endocrine biomarkers
arm group label: low-BC Group
arm group type: Active Comparator
description: consume: 1) one tablet containing 392 mg blackcurrant (BC) extract per capsule and 2) one calcium citrate caplet containing 400 mg calcium and 500 IU vitamin D
arm group label: high-BC Group
arm group type: Active Comparator
description: consume: 1) two capsules containing 392 mg BC extract per tablet (total 784 mg/day) and 2) one calcium citrate caplet containing 400 mg calcium and 500 IU vitamin D
arm group label: Control Group
arm group type: Placebo Comparator
description: consume: 1) one placebo capsule and 2) one calcium citrate caplet containing 400 mg calcium and 500 IU vitamin D
intervention type: Drug
intervention name: blackcurrant (BC) extract
description: A calcium citrate caplet (Bayer AG, Germany) will be taken by all 3 groups to avoid bone deterioration related to calcium and vitamin D deficiency
arm group label: Control Group
arm group label: high-BC Group
arm group label: low-BC Group
other name: BPE75 (392 mg and 784 mg)
criteria: 
gender: Female
gender based: Yes
gender description: perimenopausal or early postmenopausal women
minimum age: 45 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ock K Chun, PhD
role: Principal Investigator
affiliation: University of Connecticut
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Connecticut
investigator full name: Ock Chun
investigator title: Professor
mesh term: Osteoporosis
mesh term: Osteoporosis, Postmenopausal
mesh term: Cardiovascular Diseases
sharing ipd: Yes
ipd description: Once research proceedings and manuscripts are published we will make our results available both to the community of scientists interested in postmenopausal osteoporosis and to those studying the biology of inflammation-induced bone resorption to avoid unintentional duplication of research.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Unlimited time after papers are published.
ipd access criteria: Our plan of sharing of data generated by this project includes the following:
Presentations at national scientific meetings. From the projects, it is expected that approximately two presentations at national meetings would be appropriate.
Publication in peer-reviewed journals. It is our explicit intention that the study findings and key data will be placed in a readily accessible public database. All efforts will be made to rapidly release data through publication of results as quickly as possible following our analysis of the experiment data. Data used in publications will be released in a timely manner.