<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/NCT01715675</url>
  </required_header>
  <id_info>
    <org_study_id>MEC 10-3-010</org_study_id>
    <nct_id>NCT01715675</nct_id>
  </id_info>
  <brief_title>Effects of Plant Stanols on Immune Function in Asthma Patients</brief_title>
  <official_title>The Effect of Plant Stanols on the Immune Function of Asthma Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Maastricht University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Maastricht University Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Rationale: Plant stanols are well known for their effects on lowering intestinal cholesterol&#xD;
      absorption ultimately resulting in 10-15% reduced serum LDL cholesterol concentrations in&#xD;
      humans. In addition we have also shown that serum triacylglycerol (TG) concentrations may be&#xD;
      lowered in subjects with elevated baseline concentrations. Till now, there is little evidence&#xD;
      for plant stanol effects other than improving lipid profiles. However, we have very recently&#xD;
      found strong indications in ex vivo models using isolated human peripheral mononuclear blood&#xD;
      cells (PBMCs) from healthy volunteers that plant stanols have the capacity to improve immune&#xD;
      function. More into detail, plant stanols shifted the differentiation of naive T-cells into&#xD;
      the Th1 direction by activating a specific receptor present on the Antigen presenting cells&#xD;
      (APCs) and T-cells. This effect might ultimately be helpful in situations in which the&#xD;
      Th1/Th2 cell balance is disturbed into a Th2 over-responsiveness. By activating the Th1&#xD;
      response, the disturbed balance may be restored. This is for example a possibility in the&#xD;
      treatment or prevention of asthma, food allergies or HIV in susceptible subjects. In&#xD;
      addition, very recently (MEC 08-3-051) in a pilot study we also showed these ex vivo Th1&#xD;
      stimulating effects of plant stanols specifically in PBMCs isolated from asthma patients, as&#xD;
      said, a condition characterized by a Th2 dominant immune response.&#xD;
&#xD;
      Objective: The major research objective is to prove that the consumption of plant stanol&#xD;
      ester enriched yogurts can improve immune function in vivo in asthma patients.&#xD;
&#xD;
      Study design: A double-blind randomized placebo-controlled human intervention study in which&#xD;
      90 patients with clinically proven asthma will participate: 45 in the intervention group&#xD;
      receiving plant stanol yoghurt and 45 in the control group receiving a control yoghurt&#xD;
      without added plant stanols. At the end of the run-in period as well as at the end of the&#xD;
      experimental period blood will be sampled to isolate PBMCs. These cells are used to evaluate&#xD;
      effects on cytokine production, phagocytic capacity of neutrophils, and the activity of NK&#xD;
      cells. In addition, the golden standard to show improvements in immune function is by showing&#xD;
      an elevated Immunoglobulin response to a vaccine. Therefore, during the experimental period&#xD;
      all subjects receive a vaccination against Hepatitis A Virus. After 1, 2, 3, and 4 weeks&#xD;
      blood will be sampled to monitor specific immunoglobulin titers to HAV.&#xD;
&#xD;
      Study population: 90 people with clinically proven asthma, who are not carrier of hepatitis&#xD;
      A, B or C and have not been vaccinated against hepatitis A in the past. Also, these&#xD;
      participants do not have any other immune-related pathology Main study parameters/endpoints:&#xD;
      primary: Specific anti-HAV antibody titers after vaccination; secondary: Phagocytic capacity&#xD;
      of neutrophils; NK-cell activity; Th1 and Th2 cytokine production profiles by PHA stimulated&#xD;
      PMBCs.&#xD;
&#xD;
      Nature and extent of the burden and risks associated with participation, benefit and group&#xD;
      relatedness: During the study, 9 blood samples (each 20 or 50 mL) will be taken. Total time&#xD;
      investment for the subjects will be 160 min. Occasionally, a heamatoma or bruise can occur&#xD;
      during venipuncture. After the vaccination a heamatoma or a sore arm can occur. These side&#xD;
      effects should disappear within 4-5 days. Other common side effects related to the&#xD;
      vaccination are headache, loss of appetite, and fatigue, which usually will disappear within&#xD;
      24 hours.&#xD;
&#xD;
      The results of this study will show whether consumption of plant stanol enriched yogurts is&#xD;
      able to restore the disturbed th1/Th2 balance in asthma patients. Ultimately, this is&#xD;
      expected to reduce asthmatic exacerbations, as the Th2 dominant immune response seems causal&#xD;
      to asthmatic symptoms, however these clinical improvements are not verified in this&#xD;
      relatively short term intervention study.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2010</start_date>
  <completion_date type="Actual">January 2014</completion_date>
  <primary_completion_date type="Actual">May 2012</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>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>aHAV antibody titers</measure>
    <time_frame>24 hours</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma IgE</measure>
    <time_frame>24 hours</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>inflammation markers</measure>
    <time_frame>24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ex vivo cytokine production</measure>
    <time_frame>24 hours</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">61</enrollment>
  <condition>Asthma</condition>
  <condition>Allergy</condition>
  <arm_group>
    <arm_group_label>plant stanol</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Plant stanol enriched soy-based yoghurt</intervention_name>
    <description>Plant stanol enriched soy-based yoghurt</description>
    <arm_group_label>plant stanol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Soy-based yoghurt without added plant stanols</intervention_name>
    <description>Soy-based yoghurt without added plant stanols</description>
    <arm_group_label>control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  asthma&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  other inflammatory or immunological diseases dyslipideamia previous vaccination or&#xD;
             infection with hepatitis A diabetics COPD&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jogchum Plat, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Maastricht University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Maastricht University Medical Centre</name>
      <address>
        <city>Maastricht</city>
        <state>Limburg</state>
        <zip>6229ER</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>January 2014</verification_date>
  <study_first_submitted>May 30, 2012</study_first_submitted>
  <study_first_submitted_qc>October 24, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 29, 2012</study_first_posted>
  <last_update_submitted>January 9, 2014</last_update_submitted>
  <last_update_submitted_qc>January 9, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 10, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>asthma</keyword>
  <keyword>allergy</keyword>
  <keyword>sitostanol</keyword>
  <keyword>cytokines</keyword>
  <keyword>Th1</keyword>
  <keyword>Treg</keyword>
  <keyword>antibodies</keyword>
  <keyword>IgE</keyword>
  <keyword>vaccination</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Asthma</mesh_term>
  </condition_browse>
  <!-- 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/NCT01715675
org study id: MEC 10-3-010
nct id: NCT01715675
lead sponsor: 
has dmc: No
Rationale: Plant stanols are well known for their effects on lowering intestinal cholesterol
      absorption ultimately resulting in 10-15% reduced serum LDL cholesterol concentrations in
      humans. In addition we have also shown that serum triacylglycerol (TG) concentrations may be
      lowered in subjects with elevated baseline concentrations. Till now, there is little evidence
      for plant stanol effects other than improving lipid profiles. However, we have very recently
      found strong indications in ex vivo models using isolated human peripheral mononuclear blood
      cells (PBMCs) from healthy volunteers that plant stanols have the capacity to improve immune
      function. More into detail, plant stanols shifted the differentiation of naive T-cells into
      the Th1 direction by activating a specific receptor present on the Antigen presenting cells
      (APCs) and T-cells. This effect might ultimately be helpful in situations in which the
      Th1/Th2 cell balance is disturbed into a Th2 over-responsiveness. By activating the Th1
      response, the disturbed balance may be restored. This is for example a possibility in the
      treatment or prevention of asthma, food allergies or HIV in susceptible subjects. In
      addition, very recently (MEC 08-3-051) in a pilot study we also showed these ex vivo Th1
      stimulating effects of plant stanols specifically in PBMCs isolated from asthma patients, as
      said, a condition characterized by a Th2 dominant immune response.

      Objective: The major research objective is to prove that the consumption of plant stanol
      ester enriched yogurts can improve immune function in vivo in asthma patients.

      Study design: A double-blind randomized placebo-controlled human intervention study in which
      90 patients with clinically proven asthma will participate: 45 in the intervention group
      receiving plant stanol yoghurt and 45 in the control group receiving a control yoghurt
      without added plant stanols. At the end of the run-in period as well as at the end of the
      experimental period blood will be sampled to isolate PBMCs. These cells are used to evaluate
      effects on cytokine production, phagocytic capacity of neutrophils, and the activity of NK
      cells. In addition, the golden standard to show improvements in immune function is by showing
      an elevated Immunoglobulin response to a vaccine. Therefore, during the experimental period
      all subjects receive a vaccination against Hepatitis A Virus. After 1, 2, 3, and 4 weeks
      blood will be sampled to monitor specific immunoglobulin titers to HAV.

      Study population: 90 people with clinically proven asthma, who are not carrier of hepatitis
      A, B or C and have not been vaccinated against hepatitis A in the past. Also, these
      participants do not have any other immune-related pathology Main study parameters/endpoints:
      primary: Specific anti-HAV antibody titers after vaccination; secondary: Phagocytic capacity
      of neutrophils; NK-cell activity; Th1 and Th2 cytokine production profiles by PHA stimulated
      PMBCs.

      Nature and extent of the burden and risks associated with participation, benefit and group
      relatedness: During the study, 9 blood samples (each 20 or 50 mL) will be taken. Total time
      investment for the subjects will be 160 min. Occasionally, a heamatoma or bruise can occur
      during venipuncture. After the vaccination a heamatoma or a sore arm can occur. These side
      effects should disappear within 4-5 days. Other common side effects related to the
      vaccination are headache, loss of appetite, and fatigue, which usually will disappear within
      24 hours.

      The results of this study will show whether consumption of plant stanol enriched yogurts is
      able to restore the disturbed th1/Th2 balance in asthma patients. Ultimately, this is
      expected to reduce asthmatic exacerbations, as the Th2 dominant immune response seems causal
      to asthmatic symptoms, however these clinical improvements are not verified in this
      relatively short term intervention study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: aHAV antibody titers
time frame: 24 hours
measure: Plasma IgE
time frame: 24 hours
measure: inflammation markers
time frame: 24 hours
measure: ex vivo cytokine production
time frame: 24 hours
arm group label: plant stanol
arm group type: Active Comparator
arm group label: control
arm group type: Placebo Comparator
intervention type: Dietary Supplement
intervention name: Plant stanol enriched soy-based yoghurt
description: Plant stanol enriched soy-based yoghurt
arm group label: plant stanol
intervention type: Dietary Supplement
intervention name: Soy-based yoghurt without added plant stanols
description: Soy-based yoghurt without added plant stanols
arm group label: control
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Jogchum Plat, PhD
role: Principal Investigator
affiliation: Maastricht University Medical Center
facility: 
country: Netherlands
responsible party type: Sponsor
mesh term: Asthma