<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/NCT01702974</url>
  </required_header>
  <id_info>
    <org_study_id>IREHIV-2012</org_study_id>
    <nct_id>NCT01702974</nct_id>
  </id_info>
  <brief_title>Immune Reconstitution in HIV Disease (IREHIV)</brief_title>
  <acronym>IREHIV</acronym>
  <official_title>Immune Reconstitution in HIV Disease Using Antimicrobial Treatment With Vitamin D and Phenylbutyrate</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Karolinska Institutet</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Addis Ababa University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Armauer Hansen Research Institute, Ethiopia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Karolinska Institutet</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim with this study is to provide immunotherapy with vitamin D and phenylbutyrate to&#xD;
      treatment-naive HIV infected patients to induce important antimicrobial defence mechanisms&#xD;
      and decreased inflammation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">August 2015</completion_date>
  <primary_completion_date type="Actual">August 2015</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>HIV viral load</measure>
    <time_frame>0 (baseline) compared to 16 weeks.</time_frame>
    <description>Plasma HIV viral load will be used to monitor efficacy of vitamin D and phenylbutyrate treatment among treatment-naïve HIV patients at the time of diagnosis (time point 0) and at 4, 8, 16 and 24 weeks after initiation of antimicrobial treatment with vitamin D and phenylbutyrate. The primary endpoint will be assessed at 16 weeks compared to baseline (time point 0).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical secondary endpoints</measure>
    <time_frame>0, 4, 8, 16, 24 weeks.</time_frame>
    <description>Overall clinical symptoms.&#xD;
Body mass index (BMI).&#xD;
Mid upper arm circumference (MUAC).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Laboratory secondary endpoints</measure>
    <time_frame>0, 4, 8, 16, 24 weeks.</time_frame>
    <description>HIV viral load (0, 4, 8, 24 weeks).&#xD;
Peripheral CD4/CD8 T cell counts.&#xD;
Plasma levels of vitamin D, LL-37, sCD14, LPS, 16S RNA and cytokine/chemokine profiles.&#xD;
Calprotectin in feces.&#xD;
Inflammation and microbial translocation in colon punch biopsies (0 and 16 weeks).&#xD;
Functional studies of immune cells (PBMCs).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">279</enrollment>
  <condition>HIV Infection</condition>
  <arm_group>
    <arm_group_label>Vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Dose of interventions: 5,000 IU of vitamin D (cholecalciferol tablets) once daily and 500 mg PBA (sodium phenylbutyrate tablets) twice daily for 16 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo tablets</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo tablets for vitamin D once daily and placebo tablets for PBA (phenylbutyrate) twice daily for 16 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)</intervention_name>
    <description>Dose of interventions: 5,000 IU of vitamin D (cholecalciferol tablets) once daily and 500 mg PBA (sodium phenylbutyrate tablets) twice daily for 16 weeks.</description>
    <arm_group_label>Vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo tablets</intervention_name>
    <description>Placebo tablets for vitamin D once daily and placebo tablets for PBA (phenylbutyrate) twice daily for 16 weeks.</description>
    <arm_group_label>Placebo tablets</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Adult patients &gt;18 years not subjected to HAART.&#xD;
&#xD;
        HIV-1 infected patients with CD4 T cells counts &gt;200 cells/ml.&#xD;
&#xD;
        Detectable plasma viral loads &gt;1000 copies/ml.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patients on HAART or other antimicrobial drugs (including bactrim).&#xD;
&#xD;
        Antimicrobial drug treatment in the past month.&#xD;
&#xD;
        Patients with medical contra-indication for biopsy such as bleeding tendencies.&#xD;
&#xD;
        Hypercalcaemia (serum calcium &gt; 3,0 mmol/L) identified at baseline.&#xD;
&#xD;
        Pregnant and breast feeding women.&#xD;
&#xD;
        Any known liver or kidney function abnormality, malignancy or patients treated with cardiac&#xD;
        glycosides.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Susanna Brighenti, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Karolinska Institutet</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Black Lion Hospital (BLH), Addis Ababa University, Faculty of Medicine</name>
      <address>
        <city>Addis Ababa</city>
        <state>Lideta sub city</state>
        <country>Ethiopia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Ethiopia</country>
  </location_countries>
  <verification_date>February 2016</verification_date>
  <study_first_submitted>September 25, 2012</study_first_submitted>
  <study_first_submitted_qc>October 8, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 10, 2012</study_first_posted>
  <last_update_submitted>February 4, 2016</last_update_submitted>
  <last_update_submitted_qc>February 4, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 5, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Karolinska Institutet</investigator_affiliation>
    <investigator_full_name>Susanna Brighenti</investigator_full_name>
    <investigator_title>Associate professor</investigator_title>
  </responsible_party>
  <keyword>HIV</keyword>
  <keyword>cholecalciferol</keyword>
  <keyword>sodium phenylbutyrate</keyword>
  <keyword>antimicrobial peptides</keyword>
  <keyword>immune response</keyword>
  <keyword>inflammation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>HIV Infections</mesh_term>
    <mesh_term>Acquired Immunodeficiency Syndrome</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>Cholecalciferol</mesh_term>
    <mesh_term>4-phenylbutyric acid</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/NCT01702974
org study id: IREHIV-2012
nct id: NCT01702974
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
The aim with this study is to provide immunotherapy with vitamin D and phenylbutyrate to
      treatment-naive HIV infected patients to induce important antimicrobial defence mechanisms
      and decreased inflammation.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: HIV viral load
time frame: 0 (baseline) compared to 16 weeks.
description: Plasma HIV viral load will be used to monitor efficacy of vitamin D and phenylbutyrate treatment among treatment-naïve HIV patients at the time of diagnosis (time point 0) and at 4, 8, 16 and 24 weeks after initiation of antimicrobial treatment with vitamin D and phenylbutyrate. The primary endpoint will be assessed at 16 weeks compared to baseline (time point 0).
measure: Clinical secondary endpoints
time frame: 0, 4, 8, 16, 24 weeks.
description: Overall clinical symptoms.
Body mass index (BMI).
Mid upper arm circumference (MUAC).
measure: Laboratory secondary endpoints
time frame: 0, 4, 8, 16, 24 weeks.
description: HIV viral load (0, 4, 8, 24 weeks).
Peripheral CD4/CD8 T cell counts.
Plasma levels of vitamin D, LL-37, sCD14, LPS, 16S RNA and cytokine/chemokine profiles.
Calprotectin in feces.
Inflammation and microbial translocation in colon punch biopsies (0 and 16 weeks).
Functional studies of immune cells (PBMCs).
arm group label: Vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)
arm group type: Active Comparator
description: Dose of interventions: 5,000 IU of vitamin D (cholecalciferol tablets) once daily and 500 mg PBA (sodium phenylbutyrate tablets) twice daily for 16 weeks.
arm group label: Placebo tablets
arm group type: Placebo Comparator
description: Placebo tablets for vitamin D once daily and placebo tablets for PBA (phenylbutyrate) twice daily for 16 weeks.
intervention type: Drug
intervention name: vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)
description: Dose of interventions: 5,000 IU of vitamin D (cholecalciferol tablets) once daily and 500 mg PBA (sodium phenylbutyrate tablets) twice daily for 16 weeks.
arm group label: Vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)
intervention type: Drug
intervention name: Placebo tablets
description: Placebo tablets for vitamin D once daily and placebo tablets for PBA (phenylbutyrate) twice daily for 16 weeks.
arm group label: Placebo tablets
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Susanna Brighenti, PhD
role: Principal Investigator
affiliation: Karolinska Institutet
facility: 
country: Ethiopia
responsible party type: Principal Investigator
investigator affiliation: Karolinska Institutet
investigator full name: Susanna Brighenti
investigator title: Associate professor
mesh term: HIV Infections
mesh term: Acquired Immunodeficiency Syndrome
mesh term: Vitamin D
mesh term: Cholecalciferol
mesh term: 4-phenylbutyric acid