<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/NCT03026244</url>
  </required_header>
  <id_info>
    <org_study_id>NL57345.081.16</org_study_id>
    <nct_id>NCT03026244</nct_id>
  </id_info>
  <brief_title>Effect of Milk Protein and Prebiotics in Combination With Vitamin D on Innate Immunity in Elderly People</brief_title>
  <official_title>A Nutritional Intervention Study to Evaluate the Effect of Milk Protein and Prebiotics in Combination With Vitamin D on Innate Immunity in Elderly People</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NIZO Food Research</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>FrieslandCampina</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Wageningen University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>NIZO Food Research</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Rationale: The immune system in the ageing population becomes compromised with age (termed&#xD;
      &quot;Immunosenescence&quot;). Therefore, elderly people have a decreased ability to respond to&#xD;
      infection and vaccination. Furthermore, many of the health issues associated with ageing are&#xD;
      linked to inflammation (&quot;Inflammaging&quot;). It has been suggested that this compromised immune&#xD;
      function is in part due to reduced Toll-like receptor (TLR) function, which is part of the&#xD;
      innate immune system. Milk and dairy based products have been shown to have beneficial&#xD;
      effects on inflammation and immunity. This effect may be mediated via support of the innate&#xD;
      immune response and promotes TLR7 signaling in in vitro assays (unpublished observation).&#xD;
      Also prebiotics have been suggested to influence markers of innate immune function.&#xD;
      Furthermore, TLR function has been suggested to be correlated to vitamin D status. Therefore,&#xD;
      in the current pilot study, the potential of milk protein, prebiotics and vitamin D to&#xD;
      support innate immune function in elderly will be investigated.&#xD;
&#xD;
      Objective: Aim of the current study is to evaluate the effect of milk protein on the innate&#xD;
      immune response in elderly in a pilot study. Furthermore, support of this effect by&#xD;
      prebiotics and Vitamin D will be studied.&#xD;
&#xD;
      Study design: The study will be a double-blind placebo-controlled pilot study. Study&#xD;
      population: Healthy female elderly subjects of 65-85 years of age. Intervention: Period 1:&#xD;
      Milk protein or placebo. Period 2: Milk protein + prebiotics or placebo. Period 3: Milk&#xD;
      protein + prebiotics + Vitamin D or placebo.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2016</start_date>
  <completion_date type="Actual">October 2017</completion_date>
  <primary_completion_date type="Actual">October 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>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cmax of ex vivo IFN-a production by PBMCs, corrected for baseline</measure>
    <time_frame>baseline, 3 weeks, 6 weeks, 9 weeks</time_frame>
    <description>Maximum IFN-a levels after 3, 6 and 9 weeks of treatment as compared to baseline in supernatant of PBMCs ex vivo stimulated with TLR ligands.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax of ex vivo IL-6 production by PBMCs, corrected for baseline</measure>
    <time_frame>baseline, 3 weeks, 6 weeks, 9 weeks</time_frame>
    <description>Maximum IL-6 levels after 3, 6 and 9 weeks of treatment as compared to baseline in supernatant of PBMCs ex vivo stimulated with TLR ligands.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cmax of ex vivo TNF-a production by PBMCs, corrected for baseline</measure>
    <time_frame>baseline, 3 weeks, 6 weeks, 9 weeks</time_frame>
    <description>Maximum TNF-a levels after 3, 6 and 9 weeks of treatment as compared to baseline in supernatant of PBMCs ex vivo stimulated with TLR ligands.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in percentage IFN-a producing pDCs</measure>
    <time_frame>baseline, and highest percentage at either 3 weeks, 6 weeks, or 9 weeks of treatment</time_frame>
    <description>Percentage IFN-a-producing pDCs in PBMCs upon ex vivo stimulation with TLR ligands determined by flow cytometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in percentage IL-6 producing pDCs</measure>
    <time_frame>baseline, and highest percentage at either 3 weeks, 6 weeks, or 9 weeks of treatment</time_frame>
    <description>Percentage IL-6-producing pDCs in PBMCs upon ex vivo stimulation with TLR ligands determined by flow cytometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in percentage TNF-a producing pDCs</measure>
    <time_frame>baseline, and highest percentage at either 3 weeks, 6 weeks, or 9 weeks of treatment</time_frame>
    <description>Percentage TNF-a-producing pDCs in PBMCs upon ex vivo stimulation with TLR ligands determined by flow cytometry</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Immunosenescence</condition>
  <condition>Inflammation</condition>
  <arm_group>
    <arm_group_label>Nutritional intervention product</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Milk protein, prebiotics, vitamin D</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo product</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>placebo product</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Milk protein, prebiotics, vitamin D</intervention_name>
    <description>3 weeks supplementation with milk protein only, followed by 3 weeks milk protein + prebiotics, followed by 3 weeks milk protein + prebiotics + vitamin D</description>
    <arm_group_label>Nutritional intervention product</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo product</intervention_name>
    <description>3 periods of 3 weeks placebo product</description>
    <arm_group_label>Placebo product</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Female&#xD;
&#xD;
          -  Age 65-85 years&#xD;
&#xD;
          -  BMI 20-30 kg/m2&#xD;
&#xD;
          -  Non-smoking&#xD;
&#xD;
          -  Generally healthy&#xD;
&#xD;
          -  Regular and normal Dutch eating habits&#xD;
&#xD;
          -  Veins suitable for cannulation (blood sampling)&#xD;
&#xD;
          -  Voluntary participation&#xD;
&#xD;
          -  Having given written informed consent&#xD;
&#xD;
          -  Willing to comply with study procedures&#xD;
&#xD;
          -  Accept use of all encoded data, including publication, and the confidential use and&#xD;
             storage of all data for 15 years.&#xD;
&#xD;
          -  Accept disclosure of the financial benefit of participation in the study to the&#xD;
             authorities concerned&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Having chronic inflammatory or autoimmune diseases such as rheumatoid arthritis, type&#xD;
             1 diabetes, inflammatory bowel disease&#xD;
&#xD;
          -  Disease of GI tract (including major gastrointestinal tract surgery such as&#xD;
             gastrectomy, gastroenterostomy, bowel resection, known or suspected gastrointestinal&#xD;
             disorders, colon or GI tract cancer), liver, gall bladder, kidneys, thyroid gland&#xD;
&#xD;
          -  Immune-compromised&#xD;
&#xD;
          -  Use of vitamin supplements containing vitamin D and not willing to discontinue this&#xD;
             during the study&#xD;
&#xD;
          -  Use of anti-inflammatory drugs (for corticosteroids and NSAIDs : frequency &gt;1 per&#xD;
             week)&#xD;
&#xD;
          -  Use of immunosuppressive drugs&#xD;
&#xD;
          -  Excessive alcohol usage (&gt;3 consumptions/day or &gt;15 consumptions/week)&#xD;
&#xD;
          -  Participation in any clinical trial including blood sampling and/or administration of&#xD;
             substances within 60 days before inclusion in this study&#xD;
&#xD;
          -  Use of hormonal replacement therapy&#xD;
&#xD;
          -  Mental status that is incompatible with the proper conduct of the study&#xD;
&#xD;
          -  A self-reported milk allergy or sensitivity to dairy ingredients&#xD;
&#xD;
          -  Unexplained weight loss or weight gain of &gt; 3 kg in the 3 months prior to pre-study&#xD;
             screening&#xD;
&#xD;
          -  First and second degree relatives of personnel of NIZO food research or Wageningen&#xD;
             University, department of Cell Biology and Immunology or Human Nutrition&#xD;
&#xD;
          -  Not having a general practitioner&#xD;
&#xD;
          -  Not willing to accept information-transfer concerning participation in the study, or&#xD;
             information regarding his health, like laboratory results and eventual adverse events&#xD;
             to and from his general practitioner&#xD;
&#xD;
          -  Holiday to a sunny country during the study, starting from inclusion&#xD;
&#xD;
          -  Light therapy during the study, starting from inclusion&#xD;
&#xD;
          -  Use of prebiotic supplements during 2 months before study start, and during the study&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Els van Hoffen, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>NIZO Food Research</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>NIZO food research</name>
      <address>
        <city>Ede</city>
        <zip>6718 ZB</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>January 12, 2017</study_first_submitted>
  <study_first_submitted_qc>January 17, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 20, 2017</study_first_posted>
  <last_update_submitted>September 3, 2018</last_update_submitted>
  <last_update_submitted_qc>September 3, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">September 5, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Immunity</keyword>
  <keyword>Elderly</keyword>
  <keyword>Inflammation</keyword>
  <keyword>Milk protein</keyword>
  <keyword>Prebiotics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Inflammation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin D</mesh_term>
    <mesh_term>Caseins</mesh_term>
  </intervention_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/NCT03026244
org study id: NL57345.081.16
nct id: NCT03026244
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
Rationale: The immune system in the ageing population becomes compromised with age (termed
      "Immunosenescence"). Therefore, elderly people have a decreased ability to respond to
      infection and vaccination. Furthermore, many of the health issues associated with ageing are
      linked to inflammation ("Inflammaging"). It has been suggested that this compromised immune
      function is in part due to reduced Toll-like receptor (TLR) function, which is part of the
      innate immune system. Milk and dairy based products have been shown to have beneficial
      effects on inflammation and immunity. This effect may be mediated via support of the innate
      immune response and promotes TLR7 signaling in in vitro assays (unpublished observation).
      Also prebiotics have been suggested to influence markers of innate immune function.
      Furthermore, TLR function has been suggested to be correlated to vitamin D status. Therefore,
      in the current pilot study, the potential of milk protein, prebiotics and vitamin D to
      support innate immune function in elderly will be investigated.

      Objective: Aim of the current study is to evaluate the effect of milk protein on the innate
      immune response in elderly in a pilot study. Furthermore, support of this effect by
      prebiotics and Vitamin D will be studied.

      Study design: The study will be a double-blind placebo-controlled pilot study. Study
      population: Healthy female elderly subjects of 65-85 years of age. Intervention: Period 1:
      Milk protein or placebo. Period 2: Milk protein + prebiotics or placebo. Period 3: Milk
      protein + prebiotics + Vitamin D or placebo.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Cmax of ex vivo IFN-a production by PBMCs, corrected for baseline
time frame: baseline, 3 weeks, 6 weeks, 9 weeks
description: Maximum IFN-a levels after 3, 6 and 9 weeks of treatment as compared to baseline in supernatant of PBMCs ex vivo stimulated with TLR ligands.
measure: Cmax of ex vivo IL-6 production by PBMCs, corrected for baseline
time frame: baseline, 3 weeks, 6 weeks, 9 weeks
description: Maximum IL-6 levels after 3, 6 and 9 weeks of treatment as compared to baseline in supernatant of PBMCs ex vivo stimulated with TLR ligands.
measure: Cmax of ex vivo TNF-a production by PBMCs, corrected for baseline
time frame: baseline, 3 weeks, 6 weeks, 9 weeks
description: Maximum TNF-a levels after 3, 6 and 9 weeks of treatment as compared to baseline in supernatant of PBMCs ex vivo stimulated with TLR ligands.
measure: Change from baseline in percentage IFN-a producing pDCs
time frame: baseline, and highest percentage at either 3 weeks, 6 weeks, or 9 weeks of treatment
description: Percentage IFN-a-producing pDCs in PBMCs upon ex vivo stimulation with TLR ligands determined by flow cytometry
measure: Change from baseline in percentage IL-6 producing pDCs
time frame: baseline, and highest percentage at either 3 weeks, 6 weeks, or 9 weeks of treatment
description: Percentage IL-6-producing pDCs in PBMCs upon ex vivo stimulation with TLR ligands determined by flow cytometry
measure: Change from baseline in percentage TNF-a producing pDCs
time frame: baseline, and highest percentage at either 3 weeks, 6 weeks, or 9 weeks of treatment
description: Percentage TNF-a-producing pDCs in PBMCs upon ex vivo stimulation with TLR ligands determined by flow cytometry
arm group label: Nutritional intervention product
arm group type: Active Comparator
description: Milk protein, prebiotics, vitamin D
arm group label: Placebo product
arm group type: Placebo Comparator
description: placebo product
intervention type: Dietary Supplement
intervention name: Milk protein, prebiotics, vitamin D
description: 3 weeks supplementation with milk protein only, followed by 3 weeks milk protein + prebiotics, followed by 3 weeks milk protein + prebiotics + vitamin D
arm group label: Nutritional intervention product
intervention type: Dietary Supplement
intervention name: Placebo product
description: 3 periods of 3 weeks placebo product
arm group label: Placebo product
criteria: 
gender: Female
minimum age: 65 Years
maximum age: 85 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Els van Hoffen, PhD
role: Principal Investigator
affiliation: NIZO Food Research
facility: 
country: Netherlands
responsible party type: Sponsor
mesh term: Inflammation
mesh term: Vitamin D
mesh term: Caseins
sharing ipd: No