<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/NCT04423471</url>
  </required_header>
  <id_info>
    <org_study_id>PI-16-150</org_study_id>
    <nct_id>NCT04423471</nct_id>
  </id_info>
  <brief_title>Neuroinflammation, Affective and Cognitive Symptoms in Major Depression and Psoriasis</brief_title>
  <acronym>INPSYDER</acronym>
  <official_title>Neuroinflammation and Affective and Cognitive Symptoms in Patients Suffering From Major Depression and Psoriasis and Their Evolution With Treatment: A Prospective Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Germans Trias i Pujol Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Germans Trias i Pujol Hospital</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Objectives: To identify peripheral neuroinflammatory markers in patients suffering from major&#xD;
      depression or psoriasis in relation to affective symptoms (anxiety, depression,&#xD;
      irritability), fatigue and cognitive symptoms; and their change after specific treatments.&#xD;
&#xD;
      Methodology: Observational prospective cohort study in patients diagnosed with major&#xD;
      depression and patients with plaque psoriasis, who naturalistically undergo different&#xD;
      treatments (systemic or biological for psoriasis, antidepressants for depression). Forty-one&#xD;
      patients with major depression attending psychiatric consultations and 82 patients with&#xD;
      psoriasis attending dermatology consultations at Hospital Universitari Germans Trias i Pujol&#xD;
      aged 18 to 65 years old will be selected for inclusion. All of them will be assessed at&#xD;
      baseline and after 4 months treatment through a series of demographic and clinical variables,&#xD;
      psychiatric diagnosis, psychopathological scales and immunological and biochemical variables&#xD;
      after blood draw for obtaining serum, peripheral blood mononuclear cell (PBMC) and extraction&#xD;
      of total RNA. Investigators will analyze the correlation between immunological markers and&#xD;
      affective and cognitive symptoms at baseline, as well as their variation after treatment.&#xD;
      Subsequently, a bivariate comparative analysis will be carried out, where statistically&#xD;
      significant or marginally significant variables associated with psychopathological variables&#xD;
      will be used to construct a multivariate model of binary logistic regression.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Design This is a prospective observational study of cohorts with patients diagnosed with&#xD;
      major depression or psoriasis and subjected to different treatments with systemic or&#xD;
      biological drugs in the case of psoriasis, and with antidepressants in the case of major&#xD;
      depression.&#xD;
&#xD;
      Subjects of study The subjects that will participate in this study will be outpatients&#xD;
      treated in the Dermatology Consultations and the Psychiatric Consultations of the Germans&#xD;
      Trias i Pujol University Hospital (Badalona, Spain), clinically diagnosed with psoriasis or&#xD;
      major depression.&#xD;
&#xD;
      Inclusion criteria:&#xD;
&#xD;
        -  Age between 18 and 65&#xD;
&#xD;
        -  Clinical diagnosis of 1) In the psoriasis group: diagnosis of plaque psoriasis made by a&#xD;
           dermatologist, lasting at least 6 months; 2) In the major depression group: clinical&#xD;
           diagnosis of major depression according to DSM-5 criteria made by a psychiatrist.&#xD;
&#xD;
        -  Patients receiving systemic or biological treatment for psoriasis, or antidepressant for&#xD;
           major depression.&#xD;
&#xD;
      Exclusion criteria:&#xD;
&#xD;
        -  Previous treatments for psoriasis: narrow band ultraviolet B radiation (NBUBR)&#xD;
           phototherapy in the last 2 weeks; Psoralene+ultraviolet A (PUVA) phototherapy in the&#xD;
           last 4 weeks; conventional systemic treatments in the last 4 weeks; biological&#xD;
           treatments in the last 3 months&#xD;
&#xD;
        -  Previous antidepressant treatments in the last 6 weeks&#xD;
&#xD;
        -  Antipsychotic or eutimizing treatments in the last 6 weeks&#xD;
&#xD;
        -  The presence of concurrent psychotic symptoms&#xD;
&#xD;
        -  Alcohol or drug use disorders, with active consumption during the last 3 months&#xD;
&#xD;
        -  Pregnant women&#xD;
&#xD;
        -  Serious and / or unstable medical disorders, Addison or Cushing's disease, Rheumatoid&#xD;
           arthritis or systemic lupus erythematosus.&#xD;
&#xD;
      Patients will be assigned to three groups:&#xD;
&#xD;
        -  Group 1 - psoriasis patients who will receive systemic treatment (mainly methotrexate)&#xD;
&#xD;
        -  Group 2 - psoriasis patients who will receive a biological treatment&#xD;
&#xD;
        -  Group 3 - patients with major depression who will receive an antidepressant treatment&#xD;
&#xD;
      Sample's size calculation The required sample size has been calculated based on the possible&#xD;
      differences in the biomarkers: C reactive protein (CRP), interleukin IL-6, etc. Accepting an&#xD;
      alpha risk of 0.05 and a beta risk of less than 0.2 in a bilateral contrast, 41 subjects are&#xD;
      needed in each of the three groups to detect a difference equal to or greater than 2/3 of the&#xD;
      standard deviation. A follow-up loss rate of 10% has been estimated. Therefore, a total of&#xD;
      123 patients will be evaluated.&#xD;
&#xD;
      Variables&#xD;
&#xD;
        -  Sociodemographic variables: Sex / Age / Marital status / Level of studies completed /&#xD;
           Employment status&#xD;
&#xD;
        -  General clinical variables&#xD;
&#xD;
             -  Body mass index (BMI)&#xD;
&#xD;
             -  Medical comorbidities and Charlson Comorbidity Index&#xD;
&#xD;
             -  Active drug treatments&#xD;
&#xD;
        -  Clinical psoriasis variables&#xD;
&#xD;
             -  BSA (Body Surface Area). Calculation of the body surface covered by injuries.&#xD;
&#xD;
             -  PASI (Psoriasis Area and Severity Index). It is a measure of the severity and&#xD;
                overall coverage of psoriasis. All calculations are combined in a single score in&#xD;
                the range of 0 (absence of lesions) to 72 (the most severe case of psoriasis).&#xD;
                Similarly, ScalpPASI (PASI applied to the scalp) and PPPASI (PASI applied to&#xD;
                palmoplantar regions) will be calculated.&#xD;
&#xD;
             -  DLQI (Dermatology Life Quality Index). This instrument consists of 10 questions&#xD;
                covering six domains (symptoms and feelings, daily activities, leisure, work and&#xD;
                school, personal relationships and concern for the treatment of psoriasis)&#xD;
&#xD;
             -  Time since the diagnosis of psoriasis&#xD;
&#xD;
             -  Previous treatments for psoriasis&#xD;
&#xD;
        -  Clinical depression variables&#xD;
&#xD;
             -  Psychiatric diagnoses according to clinical interview and Diagnostic and&#xD;
                Statistical Manual of Mental Disorders (DSM-5) criteria (Structured Clinical&#xD;
                Interview for DSM-5 (SCID-5).&#xD;
&#xD;
             -  Age of onset and time of evolution from the first episode of major depression&#xD;
&#xD;
             -  Time of evolution of the current episode of major depression&#xD;
&#xD;
             -  Previous treatments for depression&#xD;
&#xD;
        -  Psychopathological variables&#xD;
&#xD;
             -  HADS (Hospital Anxiety and Depression Scale)&#xD;
&#xD;
             -  PHQ-9 (Patient Health Questionnaire)&#xD;
&#xD;
             -  MADRS (Montgomery Asberg Depression Rating Scale)&#xD;
&#xD;
             -  GAD-7 (Generalized Anxiety Disorder 7-item scale)&#xD;
&#xD;
             -  SHAPS (Snaith-Hamilton Pleasure Scale)&#xD;
&#xD;
             -  The Irritability Questionnaire&#xD;
&#xD;
             -  PSS (Perceived Stress Scale)&#xD;
&#xD;
             -  FSS (Fatigue Severity Scale)&#xD;
&#xD;
             -  MoCA (The Montreal Cognitive Assessment)&#xD;
&#xD;
        -  Immunological and biochemical variables:&#xD;
&#xD;
             -  Acute phase biomarkers: C Reactive Protein (CRP)&#xD;
&#xD;
             -  Proinflammatory cytokines: IL-1β, IL-6, TNF-α, IL-12, IL-23, IL-17&#xD;
&#xD;
             -  Anti-inflammatory cytokines: IL-10, IL-4, Transforming growth factor-β (TGF-β)&#xD;
&#xD;
             -  Hypothalamus-pituitary-adrenal axis (HPA): Cortisol&#xD;
&#xD;
             -  Oxidative and nitrosative stress: Zinc, Glutathione, Albumin, Uric acid, Bilirubin&#xD;
&#xD;
             -  Microglia activation: miR-155, miR-126, miR223, miR146a, miR-21, miR-124&#xD;
&#xD;
             -  Neurogenesis: Brain-derived neurotrophic factor (BDNF) in serum&#xD;
&#xD;
             -  Lymphocyte subpopulations in peripheral blood (Th1, Th2, Th17, Th1 / 17, Treg, ship&#xD;
                cells, central memory and effector memory)&#xD;
&#xD;
        -  Result variables:&#xD;
&#xD;
             -  Response to treatment (changes in PASI or MADRS scores)&#xD;
&#xD;
      Data collection and analysis All outpatients with the diagnosis of psoriasis attended in the&#xD;
      Dermatology Consultations of the Germans Trias i Pujol Hospital, as well as all those&#xD;
      patients with the diagnosis of major depression treated in the Psychiatric Consultations of&#xD;
      the same center, will be evaluated for the recruitment.&#xD;
&#xD;
        -  Recruitment visit: It will be performed by one of the dermatologists (in the psoriasis&#xD;
           group) or by one of the psychiatrists (in the major depression group) participating in&#xD;
           the study. The patient will be informed about the study and their written consent will&#xD;
           be requested. Subsequently, the inclusion and exclusion criteria will be reviewed, and&#xD;
           all demographic and clinical variables will be collected.&#xD;
&#xD;
        -  Baseline visit: A blood collection will be performed to collect serum and PBMC&#xD;
           (peripheral blood mononuclear cells). Serum samples will be centrifuged at 1750 rpm for&#xD;
           10 minutes, the supernatant will be collected and frozen at -20 ° C in the Immunology&#xD;
           Laboratory of the Germans Trias i Pujol Institute. For PBMC, Ficoll gradient&#xD;
           centrifugation of blood samples with anticoagulant will be carried out. Once the PBMCs&#xD;
           are separated, they will be frozen with 20% dimethyl sulfoxide (DMSO) in Roswell Park&#xD;
           Memorial Institute (RPMI) culture doctor with 20% fetal calf serum (FCS) and stored in&#xD;
           liquid nitrogen in the Cryobiology Platform of the Germans Trias i Pujol Institute.&#xD;
           Blood samples will also be obtained for the total extraction of RNA with 3 ml of&#xD;
           Paxgene® tubes, processed and frozen at -80 ° C in the immunology laboratory / Also in&#xD;
           this baseline visit, one of the psychiatrists will visit the patient and apply the&#xD;
           interview semi-structured clinic and psychopathological evaluation questionnaires.&#xD;
&#xD;
        -  Follow-up visit after 16 weeks of treatment: Clinical variables will be collected and&#xD;
           the same procedures as during the baseline visit will be performed.&#xD;
&#xD;
      Statistical analysis First, a descriptive analysis of the sample will be carried out.&#xD;
      Categorical variables will be summarized with frequencies and percentages, while quantitative&#xD;
      variables will be described with the mean and standard deviation if they have a normal&#xD;
      distribution, or the median and the 25th and 75th percentiles otherwise.&#xD;
&#xD;
      Secondly, the correlation between the severity of psoriasis (PASI) at the baseline visit (in&#xD;
      all patients) and the different scores of the psychopathological scales will be analyzed.&#xD;
      Since the PASI does not follow a normal distribution, it will be carried out with the&#xD;
      Spearman linear correlation test (Spearman rho).&#xD;
&#xD;
      Subsequently, a bivariate comparative analysis between the analytical and psychopathological&#xD;
      variables will be carried out. Categorical variables will be compared with Fisher's square or&#xD;
      exact Chi test, according to the application conditions, and quantitative variables with the&#xD;
      Student's T test for independent data or the non-parametric Mann-Whitney U test. The&#xD;
      statistically significant or marginally significant variables (P &lt;0.01) associated with&#xD;
      psychopathological variables in the bivariate analysis will be used to construct a&#xD;
      multivariate model of binary logistic regression, in order to evaluate the joint factors with&#xD;
      greater discrimination capacity of each of the psychopathological variables. For the model,&#xD;
      the odds ratio will be displayed along with its 95% confidence intervals and the model&#xD;
      calibration will be evaluated with the Hosmer and Lemeshow test and its ability to&#xD;
      discriminate using Receiver Operating Characteristic (ROC) curves. In all cases, P values&#xD;
      below 0.05 will be considered statistically significant. The analysis will be carried out&#xD;
      with the SPSS 22.0 software.&#xD;
&#xD;
      Limitations of the study The study is conducted in a tertiary referral hospital, so the&#xD;
      sample of patients with psoriasis or major depression may not be representative of the&#xD;
      general population of patients with these diseases.&#xD;
&#xD;
      Psychopathological measures are carried out through fully validated questionnaires in Spanish&#xD;
      in different population samples, including populations with comorbid medical conditions, but&#xD;
      not specifically in patients with psoriasis, except for DLQI.&#xD;
&#xD;
      Patients with psoriatic arthritis, although with high levels of inflammation, are likely to&#xD;
      be on chronic treatment with anti-inflammatory drugs that may affect the results. In any&#xD;
      case, the use of these treatments will be used as a covariate.&#xD;
&#xD;
      Ethical aspects The project will be submitted to the Ethical Research Committee (ERC)-Germans&#xD;
      Trias i Pujol University Hospital for approval. Subjects will be included once they have&#xD;
      given their informed consent. The ethical principles of the Declaration of Helsinki&#xD;
      (Fortaleza, 2013), the Standards of Good Clinical Practice, the legislation on biomedical&#xD;
      research (Law 14/2007), the obtaining and processing of biological samples and biobanks (RD&#xD;
      1716) will be respected. / 2011) and clinical trials with medications (RD 1090/2015). The&#xD;
      data will be processed in accordance with Organic Law 15/1999, on the Protection of Personal&#xD;
      Data.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Lack of funding&#xD;
  </why_stopped>
  <start_date type="Actual">February 1, 2021</start_date>
  <completion_date type="Anticipated">December 2022</completion_date>
  <primary_completion_date type="Anticipated">March 2022</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>3 Years</target_duration>
  <primary_outcome>
    <measure>Correlation between immunological markers and affective and cognitive symptoms at baseline.</measure>
    <time_frame>Baseline</time_frame>
    <description>To evaluate the relationship of psychiatric symptoms (affective symptoms, fatigue, cognitive deficits) and markers of inflammation, HPA axis, oxidative and nitrosative stress, gliosis and neurogenesis in both groups of psoriasic and depressive patients.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in immunological markers and affective and cognitive symptoms between baseline and after 4 months of treatment.</measure>
    <time_frame>Baseline and at 4 months</time_frame>
    <description>To evaluate the changes of psychiatric symptoms (affective symptoms, fatigue, cognitive deficits) and markers of inflammation, HPA axis, oxidative and nitrosative stress, gliosis and neurogenesis, after treatment for psoriasis with systemic or biological treatment of psoriasis and with antidepressant treatment for major depression.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Correlation between immunological markers and the course of psychiatric comorbidity in relation to anti-inflammatory treatments</measure>
    <time_frame>Baseline and at 4 months</time_frame>
    <description>To assess the relationship between the variations of the biological markers of inflammation, HPA axis, oxidative and nitrosative stress, gliosis and neurogenesis and the course of psychiatric comorbidity in relation to the different anti-inflammatory treatments for psoriasis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between the course of major depression with antidepressant treatment and biomarkers of inflammation</measure>
    <time_frame>Baseline and at 4 months</time_frame>
    <description>To evaluate the relationship between the course of major depressive illness with treatment and biomarkers of inflammation, HPA axis, oxidative and nitrosative stress, gliosis and neurogenesis</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">0</enrollment>
  <condition>Psoriasis</condition>
  <condition>Neuroinflammation</condition>
  <condition>Major Depressive Disorder</condition>
  <condition>Cognitive Symptom</condition>
  <condition>Immunological Abnormality</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <description>Psoriasis patients who will receive systemic treatment (mainly methotrexate)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <description>Psoriasis patients who will receive a biological treatment</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3</arm_group_label>
    <description>Patients with major depression who will receive an antidepressant treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Sociodemographic variables</intervention_name>
    <description>Sociodemographic variables: Sex / Age / Marital status / Level of studies completed / Employment status.&#xD;
General clinical variables: Body mass index (BMI), Medical comorbidities and Charlson Comorbidity Index, Active drug treatments&#xD;
Clinical psoriasis variables: BSA, PASI, ScalpPASI, PPPASI, DLQI, time since the diagnosis of psoriasis, previous treatments for psoriasis.&#xD;
Clinical depression variables: Psychiatric diagnoses according to clinical interview and DSM-5 criteria, age of onset and time of evolution from the first episode of major depression, time of evolution of the current episode of major depression, previous treatments for depression.&#xD;
Psychopathological variables: HADS, PHQ-9, MADRS, GAD-7, SHAPS, The Irritability Questionnaire, PSS, FSS, MoCA.&#xD;
Immunological and biochemical variables: Acute phase biomarkers, Proinflammatory cytokines, Anti-inflammatory cytokines, HPA axis, Microglia activation, Neurogenesis.&#xD;
Result variables: Changes in PASI or MADRS scores</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_label>Group 3</arm_group_label>
    <other_name>General clinical variables</other_name>
    <other_name>Clinical psoriasis variables</other_name>
    <other_name>Clinical depression variables</other_name>
    <other_name>Psychopathological variables</other_name>
    <other_name>Immunological and biochemical variables</other_name>
    <other_name>Result variables</other_name>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      A blood collection will be performed to collect serum and PBMC (peripheral blood mononuclear&#xD;
      cells). Serum samples will be centrifuged at 1750 rpm for 10 minutes, the supernatant will be&#xD;
      collected and frozen at -20 ° C. For PBMC, Ficoll gradient centrifugation of blood samples&#xD;
      with anticoagulant will be carried out. Once the PBMCs are separated, they will be frozen&#xD;
      with 20% DMSO in RPMI culture doctor with 20% fetal calf serum (FCS) and stored in liquid&#xD;
      nitrogen. Blood samples will also be obtained for the total extraction of RNA with 3 ml of&#xD;
      Paxgene® tubes, processed and frozen at -80 ° C&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The subjects that will participate in this study will be outpatients treated in the&#xD;
        External Dermatology Consultations and the External Psychiatric Consultations of the&#xD;
        Germans Trias i Pujol University Hospital (Badalona, Spain), clinically diagnosed with&#xD;
        psoriasis or major depression.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age between 18 and 65&#xD;
&#xD;
          -  Clinical diagnosis of:&#xD;
&#xD;
               -  In the psoriasis group: diagnosis of plaque psoriasis made by a dermatologist,&#xD;
                  lasting at least 6 months.&#xD;
&#xD;
               -  In the major depression group: clinical diagnosis of major depression according&#xD;
                  to DSM-5 criteria made by a psychiatrist.&#xD;
&#xD;
          -  Patients receiving systemic or biological treatment for psoriasis, or antidepressant&#xD;
             for major depression.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Previous treatments for psoriasis&#xD;
&#xD;
               -  UVBBE phototherapy in the last 2 weeks&#xD;
&#xD;
               -  PUVA phototherapy in the last 4 weeks&#xD;
&#xD;
               -  Conventional systemic treatments in the last 4 weeks&#xD;
&#xD;
               -  Biological treatments in the last 3 months&#xD;
&#xD;
          -  Previous antidepressant treatments in the last 6 weeks&#xD;
&#xD;
          -  Antipsychotic or eutimizing treatments in the last 6 weeks&#xD;
&#xD;
          -  The presence of concurrent psychotic symptoms&#xD;
&#xD;
          -  Alcohol or drug use disorders, with active consumption during the last 3 months&#xD;
&#xD;
          -  Pregnant women&#xD;
&#xD;
          -  Serious and / or unstable medical disorders, Addison or Cushing's disease, Rheumatoid&#xD;
             arthritis or systemic lupus erythematosus.&#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>Crisanto Díez-Quevedo, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Germans Trias i Pujol Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital Universitari Germans Trias i Pujol</name>
      <address>
        <city>Badalona</city>
        <state>Catalonia</state>
        <zip>08916</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>February 27, 2020</study_first_submitted>
  <study_first_submitted_qc>June 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>January 13, 2022</last_update_submitted>
  <last_update_submitted_qc>January 13, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 28, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Neuroinflammation</keyword>
  <keyword>Depression</keyword>
  <keyword>Psoriasis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neuroinflammatory Diseases</mesh_term>
    <mesh_term>Neurobehavioral Manifestations</mesh_term>
    <mesh_term>Psoriasis</mesh_term>
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
  </condition_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/NCT04423471
org study id: PI-16-150
nct id: NCT04423471
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Objectives: To identify peripheral neuroinflammatory markers in patients suffering from major
      depression or psoriasis in relation to affective symptoms (anxiety, depression,
      irritability), fatigue and cognitive symptoms; and their change after specific treatments.

      Methodology: Observational prospective cohort study in patients diagnosed with major
      depression and patients with plaque psoriasis, who naturalistically undergo different
      treatments (systemic or biological for psoriasis, antidepressants for depression). Forty-one
      patients with major depression attending psychiatric consultations and 82 patients with
      psoriasis attending dermatology consultations at Hospital Universitari Germans Trias i Pujol
      aged 18 to 65 years old will be selected for inclusion. All of them will be assessed at
      baseline and after 4 months treatment through a series of demographic and clinical variables,
      psychiatric diagnosis, psychopathological scales and immunological and biochemical variables
      after blood draw for obtaining serum, peripheral blood mononuclear cell (PBMC) and extraction
      of total RNA. Investigators will analyze the correlation between immunological markers and
      affective and cognitive symptoms at baseline, as well as their variation after treatment.
      Subsequently, a bivariate comparative analysis will be carried out, where statistically
      significant or marginally significant variables associated with psychopathological variables
      will be used to construct a multivariate model of binary logistic regression.
Design This is a prospective observational study of cohorts with patients diagnosed with
      major depression or psoriasis and subjected to different treatments with systemic or
      biological drugs in the case of psoriasis, and with antidepressants in the case of major
      depression.

      Subjects of study The subjects that will participate in this study will be outpatients
      treated in the Dermatology Consultations and the Psychiatric Consultations of the Germans
      Trias i Pujol University Hospital (Badalona, Spain), clinically diagnosed with psoriasis or
      major depression.

      Inclusion criteria:

        -  Age between 18 and 65

        -  Clinical diagnosis of 1) In the psoriasis group: diagnosis of plaque psoriasis made by a
           dermatologist, lasting at least 6 months; 2) In the major depression group: clinical
           diagnosis of major depression according to DSM-5 criteria made by a psychiatrist.

        -  Patients receiving systemic or biological treatment for psoriasis, or antidepressant for
           major depression.

      Exclusion criteria:

        -  Previous treatments for psoriasis: narrow band ultraviolet B radiation (NBUBR)
           phototherapy in the last 2 weeks; Psoralene+ultraviolet A (PUVA) phototherapy in the
           last 4 weeks; conventional systemic treatments in the last 4 weeks; biological
           treatments in the last 3 months

        -  Previous antidepressant treatments in the last 6 weeks

        -  Antipsychotic or eutimizing treatments in the last 6 weeks

        -  The presence of concurrent psychotic symptoms

        -  Alcohol or drug use disorders, with active consumption during the last 3 months

        -  Pregnant women

        -  Serious and / or unstable medical disorders, Addison or Cushing's disease, Rheumatoid
           arthritis or systemic lupus erythematosus.

      Patients will be assigned to three groups:

        -  Group 1 - psoriasis patients who will receive systemic treatment (mainly methotrexate)

        -  Group 2 - psoriasis patients who will receive a biological treatment

        -  Group 3 - patients with major depression who will receive an antidepressant treatment

      Sample's size calculation The required sample size has been calculated based on the possible
      differences in the biomarkers: C reactive protein (CRP), interleukin IL-6, etc. Accepting an
      alpha risk of 0.05 and a beta risk of less than 0.2 in a bilateral contrast, 41 subjects are
      needed in each of the three groups to detect a difference equal to or greater than 2/3 of the
      standard deviation. A follow-up loss rate of 10% has been estimated. Therefore, a total of
      123 patients will be evaluated.

      Variables

        -  Sociodemographic variables: Sex / Age / Marital status / Level of studies completed /
           Employment status

        -  General clinical variables

             -  Body mass index (BMI)

             -  Medical comorbidities and Charlson Comorbidity Index

             -  Active drug treatments

        -  Clinical psoriasis variables

             -  BSA (Body Surface Area). Calculation of the body surface covered by injuries.

             -  PASI (Psoriasis Area and Severity Index). It is a measure of the severity and
                overall coverage of psoriasis. All calculations are combined in a single score in
                the range of 0 (absence of lesions) to 72 (the most severe case of psoriasis).
                Similarly, ScalpPASI (PASI applied to the scalp) and PPPASI (PASI applied to
                palmoplantar regions) will be calculated.

             -  DLQI (Dermatology Life Quality Index). This instrument consists of 10 questions
                covering six domains (symptoms and feelings, daily activities, leisure, work and
                school, personal relationships and concern for the treatment of psoriasis)

             -  Time since the diagnosis of psoriasis

             -  Previous treatments for psoriasis

        -  Clinical depression variables

             -  Psychiatric diagnoses according to clinical interview and Diagnostic and
                Statistical Manual of Mental Disorders (DSM-5) criteria (Structured Clinical
                Interview for DSM-5 (SCID-5).

             -  Age of onset and time of evolution from the first episode of major depression

             -  Time of evolution of the current episode of major depression

             -  Previous treatments for depression

        -  Psychopathological variables

             -  HADS (Hospital Anxiety and Depression Scale)

             -  PHQ-9 (Patient Health Questionnaire)

             -  MADRS (Montgomery Asberg Depression Rating Scale)

             -  GAD-7 (Generalized Anxiety Disorder 7-item scale)

             -  SHAPS (Snaith-Hamilton Pleasure Scale)

             -  The Irritability Questionnaire

             -  PSS (Perceived Stress Scale)

             -  FSS (Fatigue Severity Scale)

             -  MoCA (The Montreal Cognitive Assessment)

        -  Immunological and biochemical variables:

             -  Acute phase biomarkers: C Reactive Protein (CRP)

             -  Proinflammatory cytokines: IL-1β, IL-6, TNF-α, IL-12, IL-23, IL-17

             -  Anti-inflammatory cytokines: IL-10, IL-4, Transforming growth factor-β (TGF-β)

             -  Hypothalamus-pituitary-adrenal axis (HPA): Cortisol

             -  Oxidative and nitrosative stress: Zinc, Glutathione, Albumin, Uric acid, Bilirubin

             -  Microglia activation: miR-155, miR-126, miR223, miR146a, miR-21, miR-124

             -  Neurogenesis: Brain-derived neurotrophic factor (BDNF) in serum

             -  Lymphocyte subpopulations in peripheral blood (Th1, Th2, Th17, Th1 / 17, Treg, ship
                cells, central memory and effector memory)

        -  Result variables:

             -  Response to treatment (changes in PASI or MADRS scores)

      Data collection and analysis All outpatients with the diagnosis of psoriasis attended in the
      Dermatology Consultations of the Germans Trias i Pujol Hospital, as well as all those
      patients with the diagnosis of major depression treated in the Psychiatric Consultations of
      the same center, will be evaluated for the recruitment.

        -  Recruitment visit: It will be performed by one of the dermatologists (in the psoriasis
           group) or by one of the psychiatrists (in the major depression group) participating in
           the study. The patient will be informed about the study and their written consent will
           be requested. Subsequently, the inclusion and exclusion criteria will be reviewed, and
           all demographic and clinical variables will be collected.

        -  Baseline visit: A blood collection will be performed to collect serum and PBMC
           (peripheral blood mononuclear cells). Serum samples will be centrifuged at 1750 rpm for
           10 minutes, the supernatant will be collected and frozen at -20 ° C in the Immunology
           Laboratory of the Germans Trias i Pujol Institute. For PBMC, Ficoll gradient
           centrifugation of blood samples with anticoagulant will be carried out. Once the PBMCs
           are separated, they will be frozen with 20% dimethyl sulfoxide (DMSO) in Roswell Park
           Memorial Institute (RPMI) culture doctor with 20% fetal calf serum (FCS) and stored in
           liquid nitrogen in the Cryobiology Platform of the Germans Trias i Pujol Institute.
           Blood samples will also be obtained for the total extraction of RNA with 3 ml of
           Paxgene® tubes, processed and frozen at -80 ° C in the immunology laboratory / Also in
           this baseline visit, one of the psychiatrists will visit the patient and apply the
           interview semi-structured clinic and psychopathological evaluation questionnaires.

        -  Follow-up visit after 16 weeks of treatment: Clinical variables will be collected and
           the same procedures as during the baseline visit will be performed.

      Statistical analysis First, a descriptive analysis of the sample will be carried out.
      Categorical variables will be summarized with frequencies and percentages, while quantitative
      variables will be described with the mean and standard deviation if they have a normal
      distribution, or the median and the 25th and 75th percentiles otherwise.

      Secondly, the correlation between the severity of psoriasis (PASI) at the baseline visit (in
      all patients) and the different scores of the psychopathological scales will be analyzed.
      Since the PASI does not follow a normal distribution, it will be carried out with the
      Spearman linear correlation test (Spearman rho).

      Subsequently, a bivariate comparative analysis between the analytical and psychopathological
      variables will be carried out. Categorical variables will be compared with Fisher's square or
      exact Chi test, according to the application conditions, and quantitative variables with the
      Student's T test for independent data or the non-parametric Mann-Whitney U test. The
      statistically significant or marginally significant variables (P <0.01) associated with
      psychopathological variables in the bivariate analysis will be used to construct a
      multivariate model of binary logistic regression, in order to evaluate the joint factors with
      greater discrimination capacity of each of the psychopathological variables. For the model,
      the odds ratio will be displayed along with its 95% confidence intervals and the model
      calibration will be evaluated with the Hosmer and Lemeshow test and its ability to
      discriminate using Receiver Operating Characteristic (ROC) curves. In all cases, P values
      below 0.05 will be considered statistically significant. The analysis will be carried out
      with the SPSS 22.0 software.

      Limitations of the study The study is conducted in a tertiary referral hospital, so the
      sample of patients with psoriasis or major depression may not be representative of the
      general population of patients with these diseases.

      Psychopathological measures are carried out through fully validated questionnaires in Spanish
      in different population samples, including populations with comorbid medical conditions, but
      not specifically in patients with psoriasis, except for DLQI.

      Patients with psoriatic arthritis, although with high levels of inflammation, are likely to
      be on chronic treatment with anti-inflammatory drugs that may affect the results. In any
      case, the use of these treatments will be used as a covariate.

      Ethical aspects The project will be submitted to the Ethical Research Committee (ERC)-Germans
      Trias i Pujol University Hospital for approval. Subjects will be included once they have
      given their informed consent. The ethical principles of the Declaration of Helsinki
      (Fortaleza, 2013), the Standards of Good Clinical Practice, the legislation on biomedical
      research (Law 14/2007), the obtaining and processing of biological samples and biobanks (RD
      1716) will be respected. / 2011) and clinical trials with medications (RD 1090/2015). The
      data will be processed in accordance with Organic Law 15/1999, on the Protection of Personal
      Data.
observational model: Cohort
time perspective: Prospective
measure: Correlation between immunological markers and affective and cognitive symptoms at baseline.
time frame: Baseline
description: To evaluate the relationship of psychiatric symptoms (affective symptoms, fatigue, cognitive deficits) and markers of inflammation, HPA axis, oxidative and nitrosative stress, gliosis and neurogenesis in both groups of psoriasic and depressive patients.
measure: Changes in immunological markers and affective and cognitive symptoms between baseline and after 4 months of treatment.
time frame: Baseline and at 4 months
description: To evaluate the changes of psychiatric symptoms (affective symptoms, fatigue, cognitive deficits) and markers of inflammation, HPA axis, oxidative and nitrosative stress, gliosis and neurogenesis, after treatment for psoriasis with systemic or biological treatment of psoriasis and with antidepressant treatment for major depression.
measure: Correlation between immunological markers and the course of psychiatric comorbidity in relation to anti-inflammatory treatments
time frame: Baseline and at 4 months
description: To assess the relationship between the variations of the biological markers of inflammation, HPA axis, oxidative and nitrosative stress, gliosis and neurogenesis and the course of psychiatric comorbidity in relation to the different anti-inflammatory treatments for psoriasis.
measure: Correlation between the course of major depression with antidepressant treatment and biomarkers of inflammation
time frame: Baseline and at 4 months
description: To evaluate the relationship between the course of major depressive illness with treatment and biomarkers of inflammation, HPA axis, oxidative and nitrosative stress, gliosis and neurogenesis
arm group label: Group 1
description: Psoriasis patients who will receive systemic treatment (mainly methotrexate)
arm group label: Group 2
description: Psoriasis patients who will receive a biological treatment
arm group label: Group 3
description: Patients with major depression who will receive an antidepressant treatment
intervention type: Diagnostic Test
intervention name: Sociodemographic variables
description: Sociodemographic variables: Sex / Age / Marital status / Level of studies completed / Employment status.
General clinical variables: Body mass index (BMI), Medical comorbidities and Charlson Comorbidity Index, Active drug treatments
Clinical psoriasis variables: BSA, PASI, ScalpPASI, PPPASI, DLQI, time since the diagnosis of psoriasis, previous treatments for psoriasis.
Clinical depression variables: Psychiatric diagnoses according to clinical interview and DSM-5 criteria, age of onset and time of evolution from the first episode of major depression, time of evolution of the current episode of major depression, previous treatments for depression.
Psychopathological variables: HADS, PHQ-9, MADRS, GAD-7, SHAPS, The Irritability Questionnaire, PSS, FSS, MoCA.
Immunological and biochemical variables: Acute phase biomarkers, Proinflammatory cytokines, Anti-inflammatory cytokines, HPA axis, Microglia activation, Neurogenesis.
Result variables: Changes in PASI or MADRS scores
arm group label: Group 1
arm group label: Group 2
arm group label: Group 3
other name: General clinical variables
other name: Clinical psoriasis variables
other name: Clinical depression variables
other name: Psychopathological variables
other name: Immunological and biochemical variables
other name: Result variables
A blood collection will be performed to collect serum and PBMC (peripheral blood mononuclear
      cells). Serum samples will be centrifuged at 1750 rpm for 10 minutes, the supernatant will be
      collected and frozen at -20 ° C. For PBMC, Ficoll gradient centrifugation of blood samples
      with anticoagulant will be carried out. Once the PBMCs are separated, they will be frozen
      with 20% DMSO in RPMI culture doctor with 20% fetal calf serum (FCS) and stored in liquid
      nitrogen. Blood samples will also be obtained for the total extraction of RNA with 3 ml of
      Paxgene® tubes, processed and frozen at -80 ° C
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Crisanto Díez-Quevedo, MD, PhD
role: Study Chair
affiliation: Germans Trias i Pujol Hospital
facility: 
country: Spain
responsible party type: Sponsor
mesh term: Neuroinflammatory Diseases
mesh term: Neurobehavioral Manifestations
mesh term: Psoriasis
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Major