<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/NCT03753867</url>
  </required_header>
  <id_info>
    <org_study_id>2018 0639</org_study_id>
    <nct_id>NCT03753867</nct_id>
  </id_info>
  <brief_title>RA Effect on Cell Surface Molecules in Vivo</brief_title>
  <official_title>Retinoic Acid Effect on Cell Surface Molecules in Vivo</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ottawa Hospital Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ottawa Hospital Research Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will follow a group of healthy male participants for about 18 weeks to see the&#xD;
      effect of taking Acitretin on their immune cells&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Retinoids have been shown in in vitro and ex vivo models to have the ability to reverse&#xD;
      latency reactivating the HIV reservoir and the potential for selective eradication of&#xD;
      HIV-harbouring cells. We feel that acitretin shows significant potential as a potential&#xD;
      adjuvant to current ART regimens, however, there is a lack of data to demonstrate that&#xD;
      treatment with acitretin at normal are able to induce molecular and transcription changes&#xD;
      consistent with the above activities. In order to provide a scientific basis for retinoid&#xD;
      therapy in HIV infection, a Phase I trial of acitretin in human subjects is proposed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    The study was withdrawn.&#xD;
  </why_stopped>
  <start_date type="Anticipated">January 7, 2019</start_date>
  <completion_date type="Anticipated">May 8, 2019</completion_date>
  <primary_completion_date type="Anticipated">May 8, 2019</primary_completion_date>
  <phase>Phase 1</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</measure>
    <time_frame>up to 5 months</time_frame>
    <description>Safety of Acitretin use in healthy volunteers will be assessed using safety labs and C-SSRS</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in α4β7 expression on peripherally circulating CD4 T cells</measure>
    <time_frame>Serial phlebotomy measured over 5 months</time_frame>
    <description>Absolute change in α4β7 expression on peripherally circulating CD4 T cells measured using flow cytometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Plasma Concentration [Cmax]</measure>
    <time_frame>Trough concentrations measured serially over 2 months of active treatment</time_frame>
    <description>Serum concentrations measured by HPLC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in RIG-1 expression, p300 expression, mTOR expression</measure>
    <time_frame>Serial phlebotomy measured over 5 months</time_frame>
    <description>Absolute change in RIG-1 expression by qRTPCR, and change in p300 expression by western blot, change in mTOR expression by qRTPCR and mTOR total/phosphorylated by western blot</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Curve [AUC]).</measure>
    <time_frame>Trough concentrations measured serially over 2 months of active treatment</time_frame>
    <description>Serum concentrations measured by HPLC</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>HIV Infections</condition>
  <arm_group>
    <arm_group_label>Acitretin treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Acitretin</intervention_name>
    <description>Acitretin will be provided to participants in the formulation Soriatane. Soriatane doses are oral tablets taken daily by the participant. Participants will then receive 35mg of oral acitretin (Soriatane) daily for 8 weeks during the intervention phase. Participants will be asked to return two months after completion of the acitretin course for clinical follow-up and additional phlebotomy for laboratory testing.</description>
    <arm_group_label>Acitretin treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male gender&#xD;
&#xD;
          2. Age 18 - 65&#xD;
&#xD;
          3. Able to provide informed consent&#xD;
&#xD;
          4. Willingness to participate in study treatment and follow-up&#xD;
&#xD;
          5. Willingness for serial phlebotomy and storage and future viro-immunological assays&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Female gender&#xD;
&#xD;
          2. Participants with a known hypersensitivity/allergy to the acitretin.&#xD;
&#xD;
          3. Participants who are actively participating in an experimental therapy study or who&#xD;
             have received experimental therapy within the last 1 year.&#xD;
&#xD;
          4. Participants who are a poor medical risk because of other systemic diseases or active&#xD;
             uncontrolled infections including HIV, Hepatitis B or C, and tuberculosis&#xD;
&#xD;
          5. Participants with impaired glucose tolerance including prediabetes or diabetes&#xD;
             mellitus, dyslipidemia, or liver dysfunction&#xD;
&#xD;
          6. Previous or current history of mood disorder, psychosis, or suicidality&#xD;
&#xD;
          7. Participants currently receiving ongoing treatment with methotrexate, tetracyclines,&#xD;
             or other retinoids&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jonathan B Angel, MD, FRCPC</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ottawa Hospital Research Institute</affiliation>
  </overall_official>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>October 1, 2018</study_first_submitted>
  <study_first_submitted_qc>November 23, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 27, 2018</study_first_posted>
  <last_update_submitted>March 2, 2020</last_update_submitted>
  <last_update_submitted_qc>March 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 4, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>HIV Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acitretin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </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/NCT03753867
org study id: 2018 0639
nct id: NCT03753867
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study will follow a group of healthy male participants for about 18 weeks to see the
      effect of taking Acitretin on their immune cells
Retinoids have been shown in in vitro and ex vivo models to have the ability to reverse
      latency reactivating the HIV reservoir and the potential for selective eradication of
      HIV-harbouring cells. We feel that acitretin shows significant potential as a potential
      adjuvant to current ART regimens, however, there is a lack of data to demonstrate that
      treatment with acitretin at normal are able to induce molecular and transcription changes
      consistent with the above activities. In order to provide a scientific basis for retinoid
      therapy in HIV infection, a Phase I trial of acitretin in human subjects is proposed.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
time frame: up to 5 months
description: Safety of Acitretin use in healthy volunteers will be assessed using safety labs and C-SSRS
measure: Change in α4β7 expression on peripherally circulating CD4 T cells
time frame: Serial phlebotomy measured over 5 months
description: Absolute change in α4β7 expression on peripherally circulating CD4 T cells measured using flow cytometry
measure: Maximum Plasma Concentration [Cmax]
time frame: Trough concentrations measured serially over 2 months of active treatment
description: Serum concentrations measured by HPLC
measure: Change in RIG-1 expression, p300 expression, mTOR expression
time frame: Serial phlebotomy measured over 5 months
description: Absolute change in RIG-1 expression by qRTPCR, and change in p300 expression by western blot, change in mTOR expression by qRTPCR and mTOR total/phosphorylated by western blot
measure: Area Under the Curve [AUC]).
time frame: Trough concentrations measured serially over 2 months of active treatment
description: Serum concentrations measured by HPLC
arm group label: Acitretin treatment
arm group type: Experimental
intervention type: Drug
intervention name: Acitretin
description: Acitretin will be provided to participants in the formulation Soriatane. Soriatane doses are oral tablets taken daily by the participant. Participants will then receive 35mg of oral acitretin (Soriatane) daily for 8 weeks during the intervention phase. Participants will be asked to return two months after completion of the acitretin course for clinical follow-up and additional phlebotomy for laboratory testing.
arm group label: Acitretin treatment
criteria: 
gender: Male
gender based: Yes
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jonathan B Angel, MD, FRCPC
role: Principal Investigator
affiliation: Ottawa Hospital Research Institute
responsible party type: Sponsor
mesh term: HIV Infections
mesh term: Acitretin
sharing ipd: Undecided