<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/NCT03774108</url>
  </required_header>
  <id_info>
    <org_study_id>114/18</org_study_id>
    <nct_id>NCT03774108</nct_id>
  </id_info>
  <brief_title>Metformin and Systemic Inflammation in HIV</brief_title>
  <acronym>Metfo</acronym>
  <official_title>Metformin Administration Effect Over Systemic Inflammation Serum Markers in HIV Positive Prediabetic Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital Civil de Guadalajara</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital Civil de Guadalajara</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purposes of this study are to find out if: metformin can be combined with anti-HIV drugs&#xD;
      to reduce systemic inflammation measured by the determination of cytokines and other series&#xD;
      of serum markers. To determine if the concomitant administration of metformin with TARA&#xD;
      improves the immune function on the CD4 T cell count and its relation with the CD8 T cells,&#xD;
      during the treatment and after its interruption.&#xD;
&#xD;
      To this end, in the present study, patients with prediabetes (who meet the fasting impaired&#xD;
      glucose criteria) will be identified and treated with metformin or placebo for 8 weeks,&#xD;
      receiving stable TARA and with a CD4 + level&gt; 200 cells / μL.&#xD;
&#xD;
      40 patients from the HIV Unit of the Civil Hospital of Guadalajara &quot;Fray Antonio Alcalde&quot;&#xD;
      will be included in this study and the intervention will last 8 weeks.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">December 15, 2018</start_date>
  <completion_date type="Anticipated">January 8, 2020</completion_date>
  <primary_completion_date type="Anticipated">December 20, 2019</primary_completion_date>
  <phase>Phase 4</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Quantification of proinflammatory cytokines serum levels by Cytometric Bead Array in prediabetic HIV positive patients after 8 weeks treatment with Metformin</measure>
    <time_frame>Basal - 8 weeks</time_frame>
    <description>Serum levels of proinflammatory cytokines will be quantify by flow cytometry using a Cytometric Bead Array. The cytokine panel to be messured will be as follows:&#xD;
IL-1beta&#xD;
IFN-alpha2&#xD;
IFN-gamma&#xD;
TNF-alpha&#xD;
MCP-1&#xD;
IL-6&#xD;
IL-8&#xD;
IL-10&#xD;
IL-12p70&#xD;
IL-17A&#xD;
IL-18&#xD;
IL-23&#xD;
IL-33&#xD;
These cytokines will be quantify in prediabetic HIV positive patients after 8 weeks treatment with Metformin</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>PreDiabetes</condition>
  <condition>HIV-1-infection</condition>
  <arm_group>
    <arm_group_label>Metformin Experimental Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Metformin 850mg/12 hours, oral, 8 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Comparator Arm</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo pills/12hours, oral, 8 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin Hydrochloride 850 MG</intervention_name>
    <description>8 weeks tratment with oral metformin</description>
    <arm_group_label>Metformin Experimental Arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>8 weeks tratment with oral placebo</description>
    <arm_group_label>Placebo Comparator Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Both sexes,&#xD;
&#xD;
          -  Age ≥18 years of age&#xD;
&#xD;
          -  With a diagnosis of HIV-1 infection,&#xD;
&#xD;
          -  That they are receiving TARE for at least 12 months (time necessary to establish a&#xD;
             stable reservoir),&#xD;
&#xD;
          -  Patients with undetectable viral load (&lt;40 copies / mL) for at least 12 months,&#xD;
&#xD;
          -  Have a CD4 + level&gt; 200 cells / μL,&#xD;
&#xD;
          -  That they do not have a diagnosis of co-infection with HCV or HBV,&#xD;
&#xD;
          -  Patients who do not have a severe alcohol intake (&lt;21 glasses / week in men and &lt;14&#xD;
             glasses / week in women),&#xD;
&#xD;
          -  Patients who do not use drugs during the last 90 days prior to the screening visit, or&#xD;
             during the study,&#xD;
&#xD;
          -  Who wish to participate voluntarily in the study and give their written consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Individuals with a known hypersensitivity / allergy to metformin.&#xD;
&#xD;
          -  Patients with contraindications to the use of metformin *.&#xD;
&#xD;
          -  Individuals who are actively involved in an experimental therapy study or who have&#xD;
             received experimental therapy in the last 6 months.&#xD;
&#xD;
          -  People suffering from stage IV-V chronic kidney disease, uncontrolled heart failure or&#xD;
             active infections.&#xD;
&#xD;
          -  Individuals with diabetes mellitus (according to the criteria of the American Diabetes&#xD;
             Association *).&#xD;
&#xD;
          -  Patients with indication for the use of statins, aspirin or immunomodulators.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Hospital Civil de Guadalajara</name>
      <address>
        <city>Guadalajara</city>
        <state>Jalisco</state>
        <zip>44280</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Mexico</country>
  </location_countries>
  <reference>
    <citation>Slim J, Saling CF. A Review of Management of Inflammation in the HIV Population. Biomed Res Int. 2016;2016:3420638. doi: 10.1155/2016/3420638. Epub 2016 Sep 27.</citation>
    <PMID>27766258</PMID>
  </reference>
  <reference>
    <citation>Arafath S, Campbell T, Yusuff J, Sharma R. Prevalence of and Risk Factors for Prediabetes in Patients Infected With HIV. Diabetes Spectr. 2018 May;31(2):139-143. doi: 10.2337/ds17-0009.</citation>
    <PMID>29773933</PMID>
  </reference>
  <reference>
    <citation>Nou E, Lo J, Grinspoon SK. Inflammation, immune activation, and cardiovascular disease in HIV. AIDS. 2016 Jun 19;30(10):1495-509. doi: 10.1097/QAD.0000000000001109.</citation>
    <PMID>27058351</PMID>
  </reference>
  <reference>
    <citation>Saisho Y. Metformin and Inflammation: Its Potential Beyond Glucose-lowering Effect. Endocr Metab Immune Disord Drug Targets. 2015;15(3):196-205. doi: 10.2174/1871530315666150316124019.</citation>
    <PMID>25772174</PMID>
  </reference>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>December 10, 2018</study_first_submitted>
  <study_first_submitted_qc>December 11, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 12, 2018</study_first_posted>
  <last_update_submitted>December 17, 2019</last_update_submitted>
  <last_update_submitted_qc>December 17, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 19, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hospital Civil de Guadalajara</investigator_affiliation>
    <investigator_full_name>Moises Ramos Solano</investigator_full_name>
    <investigator_title>Associate professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Inflammation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Data from participants will be available upon reasonable request</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Basal - 8 weeks</ipd_time_frame>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03774108
org study id: 114/18
nct id: NCT03774108
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
The purposes of this study are to find out if: metformin can be combined with anti-HIV drugs
      to reduce systemic inflammation measured by the determination of cytokines and other series
      of serum markers. To determine if the concomitant administration of metformin with TARA
      improves the immune function on the CD4 T cell count and its relation with the CD8 T cells,
      during the treatment and after its interruption.

      To this end, in the present study, patients with prediabetes (who meet the fasting impaired
      glucose criteria) will be identified and treated with metformin or placebo for 8 weeks,
      receiving stable TARA and with a CD4 + level> 200 cells / μL.

      40 patients from the HIV Unit of the Civil Hospital of Guadalajara "Fray Antonio Alcalde"
      will be included in this study and the intervention will last 8 weeks.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Quantification of proinflammatory cytokines serum levels by Cytometric Bead Array in prediabetic HIV positive patients after 8 weeks treatment with Metformin
time frame: Basal - 8 weeks
description: Serum levels of proinflammatory cytokines will be quantify by flow cytometry using a Cytometric Bead Array. The cytokine panel to be messured will be as follows:
IL-1beta
IFN-alpha2
IFN-gamma
TNF-alpha
MCP-1
IL-6
IL-8
IL-10
IL-12p70
IL-17A
IL-18
IL-23
IL-33
These cytokines will be quantify in prediabetic HIV positive patients after 8 weeks treatment with Metformin
arm group label: Metformin Experimental Arm
arm group type: Experimental
description: Metformin 850mg/12 hours, oral, 8 weeks
arm group label: Placebo Comparator Arm
arm group type: Placebo Comparator
description: Placebo pills/12hours, oral, 8 weeks
intervention type: Drug
intervention name: Metformin Hydrochloride 850 MG
description: 8 weeks tratment with oral metformin
arm group label: Metformin Experimental Arm
intervention type: Other
intervention name: Placebo
description: 8 weeks tratment with oral placebo
arm group label: Placebo Comparator Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Mexico
citation: Slim J, Saling CF. A Review of Management of Inflammation in the HIV Population. Biomed Res Int. 2016;2016:3420638. doi: 10.1155/2016/3420638. Epub 2016 Sep 27.
PMID: 27766258
citation: Arafath S, Campbell T, Yusuff J, Sharma R. Prevalence of and Risk Factors for Prediabetes in Patients Infected With HIV. Diabetes Spectr. 2018 May;31(2):139-143. doi: 10.2337/ds17-0009.
PMID: 29773933
citation: Nou E, Lo J, Grinspoon SK. Inflammation, immune activation, and cardiovascular disease in HIV. AIDS. 2016 Jun 19;30(10):1495-509. doi: 10.1097/QAD.0000000000001109.
PMID: 27058351
citation: Saisho Y. Metformin and Inflammation: Its Potential Beyond Glucose-lowering Effect. Endocr Metab Immune Disord Drug Targets. 2015;15(3):196-205. doi: 10.2174/1871530315666150316124019.
PMID: 25772174
responsible party type: Principal Investigator
investigator affiliation: Hospital Civil de Guadalajara
investigator full name: Moises Ramos Solano
investigator title: Associate professor
mesh term: Inflammation
mesh term: Metformin
sharing ipd: Yes
ipd description: Data from participants will be available upon reasonable request
ipd info type: Study Protocol
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Basal - 8 weeks