<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/NCT02217553</url>
  </required_header>
  <id_info>
    <org_study_id>1402001</org_study_id>
    <nct_id>NCT02217553</nct_id>
  </id_info>
  <brief_title>The Effect of Vitamin D Supplementation on HIV-associated Platelet Hyperreactivity</brief_title>
  <official_title>The Effect of Vitamin D Supplementation on HIV-associated Platelet Hyperreactivity</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universitas Padjadjaran</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Radboud University Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Universitas Padjadjaran</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Platelets play pivotal role in atherosclerosis and acute cardiovascular events. Platelet&#xD;
      hyperreactivity and increase platelet-monocyte aggregate (PMA) formation are found in HIV&#xD;
      infected patients, which may contribute to the excess cardiovascular risk. Low level of&#xD;
      vitamin D has been associated with the presence of cardiovascular diseases. The aim of our&#xD;
      study is to determine the effect of vitamin D supplementation on platelet activation,&#xD;
      platelet reactivity and platelet-leukocyte complex formation in asymptomatic HIV-infected&#xD;
      patients treated with ART&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. Study design A prospective intervention study. HIV-infected patients using ART and who&#xD;
           come for follow-up at the Teratai HIV clinic will be asked to participate in the study.&#xD;
           All study participants will receive vitamin D supplementation (soft gel capsule&#xD;
           containing cholecalciferol 400 IU) to be consumed 2 soft gel capsules daily for three&#xD;
           consecutive months. The effect on the platelet parameters specified above will be&#xD;
           determined before start cholecalciferol supplementation and after three months.&#xD;
&#xD;
        2. Duration of study Usually, 150 HIV-infected patients are treated with ART every week at&#xD;
           the Teratai HIV clinic of the Hasan Sadikin Hospital Bandung Indonesia. Between half&#xD;
           January 2014 and end of February 2014, 50 patients will be enrolled in this study. We&#xD;
           hypothesize that this period is long enough to include 50 patients for the present&#xD;
           study. Supplementation will take place between March and May and analysis will be done&#xD;
           in June and July. A summary of duration of study is depicted in the study timeline.&#xD;
&#xD;
        3. Study population The study population consists of adult HIV-infected patients treated&#xD;
           with ART enrolled at HIV polyclinic at Hasan Sadikin General Hospital, Bandung,&#xD;
           Indonesia.&#xD;
&#xD;
        4. Sample size calculation Our sample size calculation is based on the primary outcome,&#xD;
           which is the area under the curve (AUC) of the platelet reactivity curve with P-selectin&#xD;
           (CD62P) as platelet activation marker and ADP as platelet agonist. In a cohort of Dutch&#xD;
           HIV-infected patients we found a mean AUC of 2500 with an SD of 660. Assuming that a&#xD;
           decrease in AUC of 2500 to 2100 upon supplementation of vitamin D is clinically&#xD;
           relevant, a sample size of 23 would be sufficient using a paired design with α 0.05 and&#xD;
           a power of 80%.&#xD;
&#xD;
        5. Methods Study parameters/endpoints&#xD;
&#xD;
           There are two study parameters applied in this study:&#xD;
&#xD;
             1. Platelet reactivity, expressed as the membrane expression of the platelet&#xD;
                activation markers CD62P (P-selectin) and fibrinogen binding to integrin αIIbβ3, to&#xD;
                stimulation with increasing concentration of platelet agonists ADP.&#xD;
&#xD;
             2. Platelet-monocyte complexes.&#xD;
&#xD;
        6. Study procedures&#xD;
&#xD;
           a. Enrolment of patients During a scheduled routine polyclinic visit, the treating&#xD;
           internist will identify patients fulfilling inclusion criteria. He/she will explain the&#xD;
           background and objectives of the study to the patient. In case patients opt to&#xD;
           participate, the patient will then be asked to read and undersign the informed consent&#xD;
           form.&#xD;
&#xD;
           Venous blood (three tubes of 3 mL each) will then drawn for study purpose at enrolment&#xD;
           and after three months supplementation for:&#xD;
&#xD;
             1. 25-hydroxyvitamin D level (3 ml serum)&#xD;
&#xD;
             2. Platelet assays as specified above (3 ml CTAD)&#xD;
&#xD;
             3. Full blood count and CD4 cells (3 ml EDTA) In many instances, this will not require&#xD;
                an extra venepuncture as blood is usually collected for planned blood analysis for&#xD;
                routine clinical care during regular polyclinic visits.&#xD;
&#xD;
           Measurements and analysis consist of 25-hydroxyvitamin D level, platelet reactivity, and&#xD;
           platelet-monocyte complexes will be done when the patients participate in the study. The&#xD;
           study participants will receive 180 soft gel cholecalciferol capsules, to be taken 2&#xD;
           capsules once a day for 90 days as stated above.&#xD;
&#xD;
           As stated above, the second blood analysis will take place three months later after&#xD;
           vitamin D supplementation is completed.&#xD;
&#xD;
           b. Collection of blood samples for vitamin D level analysis As much as 3mL additional&#xD;
           blood is withdrawn while applying venepuncture for routine CD4+ measurement. Collected&#xD;
           blood is stored using red top serum tube without anticoagulant. This will take place at&#xD;
           enrolment (day 0) and after 3 months vitamin D supplementation. Each day of blood&#xD;
           withdrawal, the collected tubes are stored temporarily in wet-iced box prior transfer to&#xD;
           laboratory for vitamin D analysis. At the end of the policlinic day, all tubes are&#xD;
           transferred to the laboratory for serum separation. Then, separated serum is stored so&#xD;
           25-hydroxyvitamin D measurements can be done later. All samples are analysed for&#xD;
           25-hydroxyvitamin D measurements as well as other vitamin D metabolites such as free&#xD;
           25-hydroxyvitamin D measurements. Such analysis can not be done in Indonesia and&#xD;
           therefore samples will be shipped to the Netherlands for this purpose.&#xD;
&#xD;
           c. Collection of blood samples for platelet function analysis As specified under study&#xD;
           parameters above, platelet function analysis can be performed from one 3mL&#xD;
           citrate-anticoagulated blood tube. This will take place at enrolment (day 0) and after 3&#xD;
           months vitamin D supplementation. Each withdrawn blood from the patient, the tube is&#xD;
           directly transferred to the laboratory for platelet function within 30 minutes.&#xD;
&#xD;
           d. Full blood count and CD4 cell measurements These measurements are part of routine&#xD;
           care and will be done in the routine haematological laboratory using 3 ml EDTA blood.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2013</start_date>
  <completion_date type="Actual">June 2014</completion_date>
  <primary_completion_date type="Actual">February 2014</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The effect of vitamin D supplementation on HIV-associated platelet hyperreactivity</measure>
    <time_frame>Three months</time_frame>
    <description>Mean Fluorescence Intensity of the platelet reactivity curve before and after receiving vitamin D</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The effect of vitamin D supplementation in platelet-monocyte aggregate formation</measure>
    <time_frame>three months</time_frame>
    <description>Mean fluorescence intensity of platelet-monocyte aggregate before and after vitamin D supplementation</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Blood Platelet Disorders</condition>
  <condition>Vitamin D Deficiency</condition>
  <arm_group>
    <arm_group_label>vitamin D (cholecalciferol)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All study participants will receive vitamin D supplementation (soft gel capsule containing cholecalciferol 400 IU) to be consumed 2 soft gel capsules daily for three consecutive months. The effect on the platelet parameters specified above will be determined before start cholecalciferol supplementation and after three months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cholecalciferol</intervention_name>
    <description>The study participants will receive 180 soft gel cholecalciferol capsules, to be taken 2 capsules once a day for 90 days</description>
    <arm_group_label>vitamin D (cholecalciferol)</arm_group_label>
    <other_name>Teorol</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  &gt;18 years&#xD;
&#xD;
          -  Treated with suppressive first-line ART for at least 12 months&#xD;
&#xD;
          -  Compliant to ART and procedures of Teratai clinic&#xD;
&#xD;
          -  No signs or symptoms&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Use of aspirin or other platelet function inhibitors.&#xD;
&#xD;
          -  Any sign or symptom&#xD;
&#xD;
          -  Known active opportunistic infection&#xD;
&#xD;
          -  Active illicit drug users or any other comorbidity&#xD;
&#xD;
          -  History of failing ART or non-compliance.&#xD;
&#xD;
          -  Pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Andre van der Ven, Professor</last_name>
    <role>Study Chair</role>
    <affiliation>Radboud University Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Quirijn de Mast, Doctor</last_name>
    <role>Study Director</role>
    <affiliation>Radboud University Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Rudi Wisaksana, Doctor</last_name>
    <role>Study Director</role>
    <affiliation>Universitas Padjadjaran</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Agnes R Indrati, Doctor</last_name>
    <role>Study Director</role>
    <affiliation>Universitas Padjadjaran</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Klinik Teratai Hasan Sadikin General</name>
      <address>
        <city>Bandung</city>
        <state>West Java</state>
        <zip>40161</zip>
        <country>Indonesia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Indonesia</country>
  </location_countries>
  <link>
    <url>http://www.fk.unpad.ac.id</url>
    <description>Official web site of Faculty of Medicine, Universitas Padjadjaran</description>
  </link>
  <link>
    <url>http://www.radboudumc.nl</url>
    <description>Official web site of Radboud University Medical Center</description>
  </link>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>August 12, 2014</study_first_submitted>
  <study_first_submitted_qc>August 13, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 15, 2014</study_first_posted>
  <last_update_submitted>August 15, 2014</last_update_submitted>
  <last_update_submitted_qc>August 15, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 18, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Universitas Padjadjaran</investigator_affiliation>
    <investigator_full_name>Mohammad Ghozali</investigator_full_name>
    <investigator_title>Medical Doctor</investigator_title>
  </responsible_party>
  <keyword>platelet</keyword>
  <keyword>P-selectin</keyword>
  <keyword>platelet-fibrinogen binding</keyword>
  <keyword>platelet-monocye aggregate formation</keyword>
  <keyword>vitamin D</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Blood Platelet Disorders</mesh_term>
    <mesh_term>Vitamin D Deficiency</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cholecalciferol</mesh_term>
    <mesh_term>Vitamin D</mesh_term>
  </intervention_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/NCT02217553
org study id: 1402001
nct id: NCT02217553
lead sponsor: 
collaborator: 
has dmc: Yes
Platelets play pivotal role in atherosclerosis and acute cardiovascular events. Platelet
      hyperreactivity and increase platelet-monocyte aggregate (PMA) formation are found in HIV
      infected patients, which may contribute to the excess cardiovascular risk. Low level of
      vitamin D has been associated with the presence of cardiovascular diseases. The aim of our
      study is to determine the effect of vitamin D supplementation on platelet activation,
      platelet reactivity and platelet-leukocyte complex formation in asymptomatic HIV-infected
      patients treated with ART
1. Study design A prospective intervention study. HIV-infected patients using ART and who
           come for follow-up at the Teratai HIV clinic will be asked to participate in the study.
           All study participants will receive vitamin D supplementation (soft gel capsule
           containing cholecalciferol 400 IU) to be consumed 2 soft gel capsules daily for three
           consecutive months. The effect on the platelet parameters specified above will be
           determined before start cholecalciferol supplementation and after three months.

        2. Duration of study Usually, 150 HIV-infected patients are treated with ART every week at
           the Teratai HIV clinic of the Hasan Sadikin Hospital Bandung Indonesia. Between half
           January 2014 and end of February 2014, 50 patients will be enrolled in this study. We
           hypothesize that this period is long enough to include 50 patients for the present
           study. Supplementation will take place between March and May and analysis will be done
           in June and July. A summary of duration of study is depicted in the study timeline.

        3. Study population The study population consists of adult HIV-infected patients treated
           with ART enrolled at HIV polyclinic at Hasan Sadikin General Hospital, Bandung,
           Indonesia.

        4. Sample size calculation Our sample size calculation is based on the primary outcome,
           which is the area under the curve (AUC) of the platelet reactivity curve with P-selectin
           (CD62P) as platelet activation marker and ADP as platelet agonist. In a cohort of Dutch
           HIV-infected patients we found a mean AUC of 2500 with an SD of 660. Assuming that a
           decrease in AUC of 2500 to 2100 upon supplementation of vitamin D is clinically
           relevant, a sample size of 23 would be sufficient using a paired design with α 0.05 and
           a power of 80%.

        5. Methods Study parameters/endpoints

           There are two study parameters applied in this study:

             1. Platelet reactivity, expressed as the membrane expression of the platelet
                activation markers CD62P (P-selectin) and fibrinogen binding to integrin αIIbβ3, to
                stimulation with increasing concentration of platelet agonists ADP.

             2. Platelet-monocyte complexes.

        6. Study procedures

           a. Enrolment of patients During a scheduled routine polyclinic visit, the treating
           internist will identify patients fulfilling inclusion criteria. He/she will explain the
           background and objectives of the study to the patient. In case patients opt to
           participate, the patient will then be asked to read and undersign the informed consent
           form.

           Venous blood (three tubes of 3 mL each) will then drawn for study purpose at enrolment
           and after three months supplementation for:

             1. 25-hydroxyvitamin D level (3 ml serum)

             2. Platelet assays as specified above (3 ml CTAD)

             3. Full blood count and CD4 cells (3 ml EDTA) In many instances, this will not require
                an extra venepuncture as blood is usually collected for planned blood analysis for
                routine clinical care during regular polyclinic visits.

           Measurements and analysis consist of 25-hydroxyvitamin D level, platelet reactivity, and
           platelet-monocyte complexes will be done when the patients participate in the study. The
           study participants will receive 180 soft gel cholecalciferol capsules, to be taken 2
           capsules once a day for 90 days as stated above.

           As stated above, the second blood analysis will take place three months later after
           vitamin D supplementation is completed.

           b. Collection of blood samples for vitamin D level analysis As much as 3mL additional
           blood is withdrawn while applying venepuncture for routine CD4+ measurement. Collected
           blood is stored using red top serum tube without anticoagulant. This will take place at
           enrolment (day 0) and after 3 months vitamin D supplementation. Each day of blood
           withdrawal, the collected tubes are stored temporarily in wet-iced box prior transfer to
           laboratory for vitamin D analysis. At the end of the policlinic day, all tubes are
           transferred to the laboratory for serum separation. Then, separated serum is stored so
           25-hydroxyvitamin D measurements can be done later. All samples are analysed for
           25-hydroxyvitamin D measurements as well as other vitamin D metabolites such as free
           25-hydroxyvitamin D measurements. Such analysis can not be done in Indonesia and
           therefore samples will be shipped to the Netherlands for this purpose.

           c. Collection of blood samples for platelet function analysis As specified under study
           parameters above, platelet function analysis can be performed from one 3mL
           citrate-anticoagulated blood tube. This will take place at enrolment (day 0) and after 3
           months vitamin D supplementation. Each withdrawn blood from the patient, the tube is
           directly transferred to the laboratory for platelet function within 30 minutes.

           d. Full blood count and CD4 cell measurements These measurements are part of routine
           care and will be done in the routine haematological laboratory using 3 ml EDTA blood.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: The effect of vitamin D supplementation on HIV-associated platelet hyperreactivity
time frame: Three months
description: Mean Fluorescence Intensity of the platelet reactivity curve before and after receiving vitamin D
measure: The effect of vitamin D supplementation in platelet-monocyte aggregate formation
time frame: three months
description: Mean fluorescence intensity of platelet-monocyte aggregate before and after vitamin D supplementation
arm group label: vitamin D (cholecalciferol)
arm group type: Experimental
description: All study participants will receive vitamin D supplementation (soft gel capsule containing cholecalciferol 400 IU) to be consumed 2 soft gel capsules daily for three consecutive months. The effect on the platelet parameters specified above will be determined before start cholecalciferol supplementation and after three months.
intervention type: Drug
intervention name: Cholecalciferol
description: The study participants will receive 180 soft gel cholecalciferol capsules, to be taken 2 capsules once a day for 90 days
arm group label: vitamin D (cholecalciferol)
other name: Teorol
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Andre van der Ven, Professor
role: Study Chair
affiliation: Radboud University Medical Center
last name: Quirijn de Mast, Doctor
role: Study Director
affiliation: Radboud University Medical Center
last name: Rudi Wisaksana, Doctor
role: Study Director
affiliation: Universitas Padjadjaran
last name: Agnes R Indrati, Doctor
role: Study Director
affiliation: Universitas Padjadjaran
facility: 
country: Indonesia
url: http://www.fk.unpad.ac.id
description: Official web site of Faculty of Medicine, Universitas Padjadjaran
url: http://www.radboudumc.nl
description: Official web site of Radboud University Medical Center
responsible party type: Principal Investigator
investigator affiliation: Universitas Padjadjaran
investigator full name: Mohammad Ghozali
investigator title: Medical Doctor
mesh term: Blood Platelet Disorders
mesh term: Vitamin D Deficiency
mesh term: Cholecalciferol
mesh term: Vitamin D