<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/NCT03835546</url>
  </required_header>
  <id_info>
    <org_study_id>FLS-ANT-2015-01</org_study_id>
    <nct_id>NCT03835546</nct_id>
  </id_info>
  <brief_title>Study to Assess the ART Impact on the Brain Outcomes. The ARBRE Study</brief_title>
  <acronym>ARBRE</acronym>
  <official_title>Observational Prospective Trial to Investigate the Impact of Antiretroviral Therapy Initiation With Integrase Strand Transfer Inhibitors on Brain Outcomes:The ARBRE Study:Impact of AntiRetroviral Therapy With INSTI on BRain outcomEs (ARBRE) According to the Time of Therapy Initation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Institut de Diagnòstic per la Imatge (IDI)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Institut d'Investigació Biomèdica de Bellvitge</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Consorci Sanitari de Terrassa</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>BCN Checkpoint</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Germans Trias i Pujol Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>IrsiCaixa</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The ARBRE Study is an observational prospective trial aimed at investigating the impact of&#xD;
      the therapy initiation with INTIs on brain outcomes according to the time of therapy&#xD;
      initiation. Three study arms are considered: 1) Early treated HIV-1 infected patients (&lt;3&#xD;
      months since estimated date of infection), 2) Regularly treated HIV-1 infected patients (&gt;6&#xD;
      months since estimated date of infection), 3) Matched seronegative control group. Study&#xD;
      assessments will be performed at baseline, 1 month and 12 months. Study assessments will&#xD;
      comprise comprehensive evaluation of brain outcomes. They will include cognitive functioning,&#xD;
      neuroimaging parameters, and functional outcomes.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 26, 2015</start_date>
  <completion_date type="Actual">June 29, 2018</completion_date>
  <primary_completion_date type="Actual">December 23, 2016</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Global Cognitive Functioning</measure>
    <time_frame>From Baseline to Week 48</time_frame>
    <description>The measure used will be NPZ-12 (NeuroPsychological Z-12). Minimum value: -5 Maximum value: +5. Mean: 0. Lower score will represent worse global cognitive functioning; higher score will represent better global cognitive functioning.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Neuropsychiatric Symptoms</measure>
    <time_frame>From Baseline to Week 48</time_frame>
    <description>The measure used will be a checklist of symptoms involving the central nervous system. Minimum value: 0; Maximum value: 140. Lower score will represent better neuropsychiatric status; higher score will represent worse neuropsychiatric status.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Daily Living Functioning</measure>
    <time_frame>From Baseline to Week 48</time_frame>
    <description>Daily living functioning will be measured by a self-reported scale indicating daily living areas impaired. Minimum score: 0; Maximum score: 13. A lower score will represent better daily functioning; a higher score will represent worse daily functioning.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Depressive Symptoms</measure>
    <time_frame>From baseline to week 48</time_frame>
    <description>Depressive symptoms will be measured by a self-reported scale that will assess depressive symptoms. Minimum score: 0; Maximum score: 21. A lower score will represent better depressive status; a higher score will represent worse depressive status.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Anxiety Symptoms</measure>
    <time_frame>From Baseline to Week 48</time_frame>
    <description>Anxiety symptoms will be measured by a self-reported scale that will assess anxiety symptoms. Minimum score: 0; Maximum score: 21. A lower score will represent better anxiety status; a higher score will represent worse anxiety status.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Daily Perceived Stress</measure>
    <time_frame>From baseline to week 48</time_frame>
    <description>Perceived stress will be measured by a self-reported scale that will assess daily symptoms of perceived stress. Minimum score: 0; Maximum score: 40. A lower score will represent better perceived stress status; a higher score will represent worse perceived stress status.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Quality of Life</measure>
    <time_frame>From Baseline to Week 48</time_frame>
    <description>Quality of life will be measured by a self-reported scale that will assess global quality of life. Minimum score: 1; Maximum score: 4. A lower score will represent worse quality of life; a higher score will represent better quality of life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Neuroimaging Markers</measure>
    <time_frame>From Baseline to Week 48</time_frame>
    <description>Neuroimaging markers will be assessed by 3T magnetic resonance imaging (MRI). The specific markers will be caudate nucleus, ventral striatum/nucleus accumbens, putamen, pallidum, thalamus, dorsomedial, dorsolateral, cingulate, ventromedial, medial orbitofrontal, and lateral orbitofrontal cortex. The outcome will be based on change in any of them.</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">45</enrollment>
  <condition>HIV-1 Infection</condition>
  <condition>Cognitive Impairment</condition>
  <arm_group>
    <arm_group_label>Early treated patients</arm_group_label>
    <description>Patients with confirmed HIV-1 infection attended in the HIV Unit of the Hospital Universitari Germans Trias i Pujol who initiated therapy presenting recent HIV-1 infection. Recent HIV-1 infection was defined as having a positive plasma viral load and/or p24 antigen with a negative ELISA or having a positive ELISA and undetermined Western-Blot, or having a positive ELISA and absence of p31 antigen in a positive Western-Blot, or seroconversion ELISA in less than 3 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Regularly treated patients</arm_group_label>
    <description>Patients with confirmed HIV-1 infection attended in the HIV Unit of the Hospital Universitari Germans Trias i Pujol who initiated therapy, did not fulfil the criteria for recent HIV-1 infection, and had an estimated time &gt;6 months reported by the patient and/or by the responsible physician since HIV transmission.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Seronegative volunteers</arm_group_label>
    <description>HIV-uninfected volunteers, matched to age, sex, and educational level with groups A and B.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        HIV patients early treated HIV chronically patients non HIV participants&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        The study criteria for participation in the study will be the following:&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18-65 years old&#xD;
&#xD;
          -  Voluntary participation.&#xD;
&#xD;
          -  Signed written consent.&#xD;
&#xD;
          -  Confirmed HIV-1 infection (for arms A and B).&#xD;
&#xD;
          -  Intention to initiate therapy with cART containing an INSTI. Specifically, the regimen&#xD;
             included raltegravir, elvitegravir or dolutegravir.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior diagnosis of opportunistic infection involving CNS.&#xD;
&#xD;
          -  Current diagnosis of psychiatric disorder.&#xD;
&#xD;
          -  Current or past diagnosis of neurologic disease.&#xD;
&#xD;
          -  Inability to develop any of the tasks required for the study.&#xD;
&#xD;
          -  Pregnancy.&#xD;
&#xD;
          -  History of suboptimal adherence (for arms A and B).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jose A. Muñoz-Moreno</last_name>
    <role>Principal Investigator</role>
    <affiliation>Lluita contra la Sida Foundation</affiliation>
  </overall_official>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>September 25, 2018</study_first_submitted>
  <study_first_submitted_qc>February 7, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 8, 2019</study_first_posted>
  <results_first_submitted>April 10, 2020</results_first_submitted>
  <results_first_submitted_qc>May 15, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">June 1, 2020</results_first_posted>
  <last_update_submitted>May 15, 2020</last_update_submitted>
  <last_update_submitted_qc>May 15, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 1, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Brain</keyword>
  <keyword>HIV-1 Infection</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Cognitive Dysfunction</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Early Treated Patients</title>
          <description>Patients with confirmed HIV-1 infection attended in the HIV Unit of the Hospital Universitari Germans Trias i Pujol who initiated therapy presenting recent HIV-1 infection. Recent HIV-1 infection was defined as having a positive plasma viral load and/or p24 antigen with a negative ELISA or having a positive ELISA and undetermined Western-Blot, or having a positive ELISA and absence of p31 antigen in a positive Western-Blot, or seroconversion ELISA in less than 3 months.</description>
        </group>
        <group group_id="P2">
          <title>Regularly Treated Patients</title>
          <description>Patients with confirmed HIV-1 infection attended in the HIV Unit of the Hospital Universitari Germans Trias i Pujol who initiated therapy, did not fulfil the criteria for recent HIV-1 infection, and had an estimated time &gt;6 months reported by the patient and/or by the responsible physician since HIV transmission.</description>
        </group>
        <group group_id="P3">
          <title>Seronegative Volunteers</title>
          <description>HIV-uninfected volunteers, matched to age, sex, and educational level with groups A and B.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="15"/>
                <participants group_id="P3" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="15"/>
                <participants group_id="P3" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Early Treated Patients</title>
          <description>Patients with confirmed HIV-1 infection attended in the HIV Unit of the Hospital Universitari Germans Trias i Pujol who initiated therapy presenting recent HIV-1 infection. Recent HIV-1 infection was defined as having a positive plasma viral load and/or p24 antigen with a negative ELISA or having a positive ELISA and undetermined Western-Blot, or having a positive ELISA and absence of p31 antigen in a positive Western-Blot, or seroconversion ELISA in less than 3 months.</description>
        </group>
        <group group_id="B2">
          <title>Regularly Treated Patients</title>
          <description>Patients with confirmed HIV-1 infection attended in the HIV Unit of the Hospital Universitari Germans Trias i Pujol who initiated therapy, did not fulfil the criteria for recent HIV-1 infection, and had an estimated time &gt;6 months reported by the patient and/or by the responsible physician since HIV transmission.</description>
        </group>
        <group group_id="B3">
          <title>Seronegative Volunteers</title>
          <description>HIV-uninfected volunteers, matched to age, sex, and educational level with groups A and B.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="12"/>
            <count group_id="B2" value="15"/>
            <count group_id="B3" value="15"/>
            <count group_id="B4" value="42"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="15"/>
                    <measurement group_id="B4" value="42"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="34" spread="10"/>
                    <measurement group_id="B2" value="31" spread="9"/>
                    <measurement group_id="B3" value="32" spread="10"/>
                    <measurement group_id="B4" value="32" spread="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="15"/>
                    <measurement group_id="B4" value="42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="15"/>
                    <measurement group_id="B4" value="42"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Spain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="15"/>
                    <measurement group_id="B4" value="42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Global Cognitive Functioning</title>
        <description>The measure used will be NPZ-12 (NeuroPsychological Z-12). Minimum value: -5 Maximum value: +5. Mean: 0. Lower score will represent worse global cognitive functioning; higher score will represent better global cognitive functioning.</description>
        <time_frame>From Baseline to Week 48</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Early Treated Patients</title>
            <description>Patients with confirmed HIV-1 infection attended in the HIV Unit of the Hospital Universitari Germans Trias i Pujol who initiated therapy presenting recent HIV-1 infection. Recent HIV-1 infection was defined as having a positive plasma viral load and/or p24 antigen with a negative ELISA or having a positive ELISA and undetermined Western-Blot, or having a positive ELISA and absence of p31 antigen in a positive Western-Blot, or seroconversion ELISA in less than 3 months.</description>
          </group>
          <group group_id="O2">
            <title>Regularly Treated Patients</title>
            <description>Patients with confirmed HIV-1 infection attended in the HIV Unit of the Hospital Universitari Germans Trias i Pujol who initiated therapy, did not fulfil the criteria for recent HIV-1 infection, and had an estimated time &gt;6 months reported by the patient and/or by the responsible physician since HIV transmission.</description>
          </group>
          <group group_id="O3">
            <title>Seronegative Volunteers</title>
            <description>HIV-uninfected volunteers, matched to age, sex, and educational level with groups A and B.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Global Cognitive Functioning</title>
          <description>The measure used will be NPZ-12 (NeuroPsychological Z-12). Minimum value: -5 Maximum value: +5. Mean: 0. Lower score will represent worse global cognitive functioning; higher score will represent better global cognitive functioning.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.08" spread="0.26"/>
                    <measurement group_id="O2" value="0.31" spread="0.28"/>
                    <measurement group_id="O3" value="0.25" spread="0.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Neuropsychiatric Symptoms</title>
        <description>The measure used will be a checklist of symptoms involving the central nervous system. Minimum value: 0; Maximum value: 140. Lower score will represent better neuropsychiatric status; higher score will represent worse neuropsychiatric status.</description>
        <time_frame>From Baseline to Week 48</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Early Treated Patients</title>
            <description>Patients with confirmed HIV-1 infection attended in the HIV Unit of the Hospital Universitari Germans Trias i Pujol who initiated therapy presenting recent HIV-1 infection. Recent HIV-1 infection was defined as having a positive plasma viral load and/or p24 antigen with a negative ELISA or having a positive ELISA and undetermined Western-Blot, or having a positive ELISA and absence of p31 antigen in a positive Western-Blot, or seroconversion ELISA in less than 3 months.</description>
          </group>
          <group group_id="O2">
            <title>Regularly Treated Patients</title>
            <description>Patients with confirmed HIV-1 infection attended in the HIV Unit of the Hospital Universitari Germans Trias i Pujol who initiated therapy, did not fulfil the criteria for recent HIV-1 infection, and had an estimated time &gt;6 months reported by the patient and/or by the responsible physician since HIV transmission.</description>
          </group>
          <group group_id="O3">
            <title>Seronegative Volunteers</title>
            <description>HIV-uninfected volunteers, matched to age, sex, and educational level with groups A and B.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Neuropsychiatric Symptoms</title>
          <description>The measure used will be a checklist of symptoms involving the central nervous system. Minimum value: 0; Maximum value: 140. Lower score will represent better neuropsychiatric status; higher score will represent worse neuropsychiatric status.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.90" spread="8.76"/>
                    <measurement group_id="O2" value="0.33" spread="7.58"/>
                    <measurement group_id="O3" value="0.30" spread="5.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Daily Living Functioning</title>
        <description>Daily living functioning will be measured by a self-reported scale indicating daily living areas impaired. Minimum score: 0; Maximum score: 13. A lower score will represent better daily functioning; a higher score will represent worse daily functioning.</description>
        <time_frame>From Baseline to Week 48</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Early Treated Patients</title>
            <description>Patients with confirmed HIV-1 infection attended in the HIV Unit of the Hospital Universitari Germans Trias i Pujol who initiated therapy presenting recent HIV-1 infection. Recent HIV-1 infection was defined as having a positive plasma viral load and/or p24 antigen with a negative ELISA or having a positive ELISA and undetermined Western-Blot, or having a positive ELISA and absence of p31 antigen in a positive Western-Blot, or seroconversion ELISA in less than 3 months.</description>
          </group>
          <group group_id="O2">
            <title>Regularly Treated Patients</title>
            <description>Patients with confirmed HIV-1 infection attended in the HIV Unit of the Hospital Universitari Germans Trias i Pujol who initiated therapy, did not fulfil the criteria for recent HIV-1 infection, and had an estimated time &gt;6 months reported by the patient and/or by the responsible physician since HIV transmission.</description>
          </group>
          <group group_id="O3">
            <title>Seronegative Volunteers</title>
            <description>HIV-uninfected volunteers, matched to age, sex, and educational level with groups A and B.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Daily Living Functioning</title>
          <description>Daily living functioning will be measured by a self-reported scale indicating daily living areas impaired. Minimum score: 0; Maximum score: 13. A lower score will represent better daily functioning; a higher score will represent worse daily functioning.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.54" spread="1.69"/>
                    <measurement group_id="O2" value="0.33" spread="2.01"/>
                    <measurement group_id="O3" value="0.30" spread="0.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Depressive Symptoms</title>
        <description>Depressive symptoms will be measured by a self-reported scale that will assess depressive symptoms. Minimum score: 0; Maximum score: 21. A lower score will represent better depressive status; a higher score will represent worse depressive status.</description>
        <time_frame>From baseline to week 48</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Early Treated Patients</title>
            <description>Patients with confirmed HIV-1 infection attended in the HIV Unit of the Hospital Universitari Germans Trias i Pujol who initiated therapy presenting recent HIV-1 infection. Recent HIV-1 infection was defined as having a positive plasma viral load and/or p24 antigen with a negative ELISA or having a positive ELISA and undetermined Western-Blot, or having a positive ELISA and absence of p31 antigen in a positive Western-Blot, or seroconversion ELISA in less than 3 months.</description>
          </group>
          <group group_id="O2">
            <title>Regularly Treated Patients</title>
            <description>Patients with confirmed HIV-1 infection attended in the HIV Unit of the Hospital Universitari Germans Trias i Pujol who initiated therapy, did not fulfil the criteria for recent HIV-1 infection, and had an estimated time &gt;6 months reported by the patient and/or by the responsible physician since HIV transmission.</description>
          </group>
          <group group_id="O3">
            <title>Seronegative Volunteers</title>
            <description>HIV-uninfected volunteers, matched to age, sex, and educational level with groups A and B.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Depressive Symptoms</title>
          <description>Depressive symptoms will be measured by a self-reported scale that will assess depressive symptoms. Minimum score: 0; Maximum score: 21. A lower score will represent better depressive status; a higher score will represent worse depressive status.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.55" spread="2.58"/>
                    <measurement group_id="O2" value="-0.50" spread="3.84"/>
                    <measurement group_id="O3" value="-0.60" spread="1.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Anxiety Symptoms</title>
        <description>Anxiety symptoms will be measured by a self-reported scale that will assess anxiety symptoms. Minimum score: 0; Maximum score: 21. A lower score will represent better anxiety status; a higher score will represent worse anxiety status.</description>
        <time_frame>From Baseline to Week 48</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Early Treated Patients</title>
            <description>Patients with confirmed HIV-1 infection attended in the HIV Unit of the Hospital Universitari Germans Trias i Pujol who initiated therapy presenting recent HIV-1 infection. Recent HIV-1 infection was defined as having a positive plasma viral load and/or p24 antigen with a negative ELISA or having a positive ELISA and undetermined Western-Blot, or having a positive ELISA and absence of p31 antigen in a positive Western-Blot, or seroconversion ELISA in less than 3 months.</description>
          </group>
          <group group_id="O2">
            <title>Regularly Treated Patients</title>
            <description>Patients with confirmed HIV-1 infection attended in the HIV Unit of the Hospital Universitari Germans Trias i Pujol who initiated therapy, did not fulfil the criteria for recent HIV-1 infection, and had an estimated time &gt;6 months reported by the patient and/or by the responsible physician since HIV transmission.</description>
          </group>
          <group group_id="O3">
            <title>Seronegative Volunteers</title>
            <description>HIV-uninfected volunteers, matched to age, sex, and educational level with groups A and B.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Anxiety Symptoms</title>
          <description>Anxiety symptoms will be measured by a self-reported scale that will assess anxiety symptoms. Minimum score: 0; Maximum score: 21. A lower score will represent better anxiety status; a higher score will represent worse anxiety status.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.18" spread="3.46"/>
                    <measurement group_id="O2" value="-2.00" spread="2.93"/>
                    <measurement group_id="O3" value="-1.30" spread="2.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Daily Perceived Stress</title>
        <description>Perceived stress will be measured by a self-reported scale that will assess daily symptoms of perceived stress. Minimum score: 0; Maximum score: 40. A lower score will represent better perceived stress status; a higher score will represent worse perceived stress status.</description>
        <time_frame>From baseline to week 48</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Early Treated Patients</title>
            <description>Patients with confirmed HIV-1 infection attended in the HIV Unit of the Hospital Universitari Germans Trias i Pujol who initiated therapy presenting recent HIV-1 infection. Recent HIV-1 infection was defined as having a positive plasma viral load and/or p24 antigen with a negative ELISA or having a positive ELISA and undetermined Western-Blot, or having a positive ELISA and absence of p31 antigen in a positive Western-Blot, or seroconversion ELISA in less than 3 months.</description>
          </group>
          <group group_id="O2">
            <title>Regularly Treated Patients</title>
            <description>Patients with confirmed HIV-1 infection attended in the HIV Unit of the Hospital Universitari Germans Trias i Pujol who initiated therapy, did not fulfil the criteria for recent HIV-1 infection, and had an estimated time &gt;6 months reported by the patient and/or by the responsible physician since HIV transmission.</description>
          </group>
          <group group_id="O3">
            <title>Seronegative Volunteers</title>
            <description>HIV-uninfected volunteers, matched to age, sex, and educational level with groups A and B.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Daily Perceived Stress</title>
          <description>Perceived stress will be measured by a self-reported scale that will assess daily symptoms of perceived stress. Minimum score: 0; Maximum score: 40. A lower score will represent better perceived stress status; a higher score will represent worse perceived stress status.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.55" spread="3.88"/>
                    <measurement group_id="O2" value="-6.50" spread="9.24"/>
                    <measurement group_id="O3" value="1.40" spread="4.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Quality of Life</title>
        <description>Quality of life will be measured by a self-reported scale that will assess global quality of life. Minimum score: 1; Maximum score: 4. A lower score will represent worse quality of life; a higher score will represent better quality of life.</description>
        <time_frame>From Baseline to Week 48</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Early Treated Patients</title>
            <description>Patients with confirmed HIV-1 infection attended in the HIV Unit of the Hospital Universitari Germans Trias i Pujol who initiated therapy presenting recent HIV-1 infection. Recent HIV-1 infection was defined as having a positive plasma viral load and/or p24 antigen with a negative ELISA or having a positive ELISA and undetermined Western-Blot, or having a positive ELISA and absence of p31 antigen in a positive Western-Blot, or seroconversion ELISA in less than 3 months.</description>
          </group>
          <group group_id="O2">
            <title>Regularly Treated Patients</title>
            <description>Patients with confirmed HIV-1 infection attended in the HIV Unit of the Hospital Universitari Germans Trias i Pujol who initiated therapy, did not fulfil the criteria for recent HIV-1 infection, and had an estimated time &gt;6 months reported by the patient and/or by the responsible physician since HIV transmission.</description>
          </group>
          <group group_id="O3">
            <title>Seronegative Volunteers</title>
            <description>HIV-uninfected volunteers, matched to age, sex, and educational level with groups A and B.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Quality of Life</title>
          <description>Quality of life will be measured by a self-reported scale that will assess global quality of life. Minimum score: 1; Maximum score: 4. A lower score will represent worse quality of life; a higher score will represent better quality of life.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.18" spread="0.40"/>
                    <measurement group_id="O2" value="0.08" spread="0.51"/>
                    <measurement group_id="O3" value="0.10" spread="0.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Neuroimaging Markers</title>
        <description>Neuroimaging markers will be assessed by 3T magnetic resonance imaging (MRI). The specific markers will be caudate nucleus, ventral striatum/nucleus accumbens, putamen, pallidum, thalamus, dorsomedial, dorsolateral, cingulate, ventromedial, medial orbitofrontal, and lateral orbitofrontal cortex. The outcome will be based on change in any of them.</description>
        <time_frame>From Baseline to Week 48</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From Baseline to week 48</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Early Treated Patients</title>
          <description>Patients with confirmed HIV-1 infection attended in the HIV Unit of the Hospital Universitari Germans Trias i Pujol who initiated therapy presenting recent HIV-1 infection. Recent HIV-1 infection was defined as having a positive plasma viral load and/or p24 antigen with a negative ELISA or having a positive ELISA and undetermined Western-Blot, or having a positive ELISA and absence of p31 antigen in a positive Western-Blot, or seroconversion ELISA in less than 3 months.</description>
        </group>
        <group group_id="E2">
          <title>Regularly Treated Patients</title>
          <description>Patients with confirmed HIV-1 infection attended in the HIV Unit of the Hospital Universitari Germans Trias i Pujol who initiated therapy, did not fulfil the criteria for recent HIV-1 infection, and had an estimated time &gt;6 months reported by the patient and/or by the responsible physician since HIV transmission.</description>
        </group>
        <group group_id="E3">
          <title>Seronegative Volunteers</title>
          <description>HIV-uninfected volunteers, matched to age, sex, and educational level with groups A and B.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Jose A. Muñoz-Moreno</name_or_title>
      <organization>Fundació Lluita contra la SIDA</organization>
      <phone>+34 93 497 84 14</phone>
      <email>jmunoz@flsida.org</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03835546
org study id: FLS-ANT-2015-01
nct id: NCT03835546
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
The ARBRE Study is an observational prospective trial aimed at investigating the impact of
      the therapy initiation with INTIs on brain outcomes according to the time of therapy
      initiation. Three study arms are considered: 1) Early treated HIV-1 infected patients (<3
      months since estimated date of infection), 2) Regularly treated HIV-1 infected patients (>6
      months since estimated date of infection), 3) Matched seronegative control group. Study
      assessments will be performed at baseline, 1 month and 12 months. Study assessments will
      comprise comprehensive evaluation of brain outcomes. They will include cognitive functioning,
      neuroimaging parameters, and functional outcomes.
observational model: Other
time perspective: Prospective
measure: Change in Global Cognitive Functioning
time frame: From Baseline to Week 48
description: The measure used will be NPZ-12 (NeuroPsychological Z-12). Minimum value: -5 Maximum value: +5. Mean: 0. Lower score will represent worse global cognitive functioning; higher score will represent better global cognitive functioning.
measure: Change in Neuropsychiatric Symptoms
time frame: From Baseline to Week 48
description: The measure used will be a checklist of symptoms involving the central nervous system. Minimum value: 0; Maximum value: 140. Lower score will represent better neuropsychiatric status; higher score will represent worse neuropsychiatric status.
measure: Change in Daily Living Functioning
time frame: From Baseline to Week 48
description: Daily living functioning will be measured by a self-reported scale indicating daily living areas impaired. Minimum score: 0; Maximum score: 13. A lower score will represent better daily functioning; a higher score will represent worse daily functioning.
measure: Change in Depressive Symptoms
time frame: From baseline to week 48
description: Depressive symptoms will be measured by a self-reported scale that will assess depressive symptoms. Minimum score: 0; Maximum score: 21. A lower score will represent better depressive status; a higher score will represent worse depressive status.
measure: Change in Anxiety Symptoms
time frame: From Baseline to Week 48
description: Anxiety symptoms will be measured by a self-reported scale that will assess anxiety symptoms. Minimum score: 0; Maximum score: 21. A lower score will represent better anxiety status; a higher score will represent worse anxiety status.
measure: Change in Daily Perceived Stress
time frame: From baseline to week 48
description: Perceived stress will be measured by a self-reported scale that will assess daily symptoms of perceived stress. Minimum score: 0; Maximum score: 40. A lower score will represent better perceived stress status; a higher score will represent worse perceived stress status.
measure: Change in Quality of Life
time frame: From Baseline to Week 48
description: Quality of life will be measured by a self-reported scale that will assess global quality of life. Minimum score: 1; Maximum score: 4. A lower score will represent worse quality of life; a higher score will represent better quality of life.
measure: Change in Neuroimaging Markers
time frame: From Baseline to Week 48
description: Neuroimaging markers will be assessed by 3T magnetic resonance imaging (MRI). The specific markers will be caudate nucleus, ventral striatum/nucleus accumbens, putamen, pallidum, thalamus, dorsomedial, dorsolateral, cingulate, ventromedial, medial orbitofrontal, and lateral orbitofrontal cortex. The outcome will be based on change in any of them.
arm group label: Early treated patients
description: Patients with confirmed HIV-1 infection attended in the HIV Unit of the Hospital Universitari Germans Trias i Pujol who initiated therapy presenting recent HIV-1 infection. Recent HIV-1 infection was defined as having a positive plasma viral load and/or p24 antigen with a negative ELISA or having a positive ELISA and undetermined Western-Blot, or having a positive ELISA and absence of p31 antigen in a positive Western-Blot, or seroconversion ELISA in less than 3 months.
arm group label: Regularly treated patients
description: Patients with confirmed HIV-1 infection attended in the HIV Unit of the Hospital Universitari Germans Trias i Pujol who initiated therapy, did not fulfil the criteria for recent HIV-1 infection, and had an estimated time >6 months reported by the patient and/or by the responsible physician since HIV transmission.
arm group label: Seronegative volunteers
description: HIV-uninfected volunteers, matched to age, sex, and educational level with groups A and B.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Jose A. Muñoz-Moreno
role: Principal Investigator
affiliation: Lluita contra la Sida Foundation
responsible party type: Sponsor
mesh term: Infections
mesh term: Cognitive Dysfunction
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 