<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/NCT03014518</url>
  </required_header>
  <id_info>
    <org_study_id>16-630</org_study_id>
    <secondary_id>MH108857</secondary_id>
    <nct_id>NCT03014518</nct_id>
  </id_info>
  <brief_title>Biomarkers as Predictors of Suicidal Risk in Adolescents</brief_title>
  <official_title>Peripheral Neuroinflammatory Predictors of Suicidal Risk at Time of Inpatient Discharge in Adolescents</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Cleveland Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Case Western Reserve University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Van Andel Research Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Mental Health (NIMH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>The Cleveland Clinic</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Suicide is one of the most devastating events in society at all levels. The primary goal of&#xD;
      this study is to predict suicide in adolescents at risk. We will utilize blood biomarker&#xD;
      measurement and clinical risk factor scales to develop a tool to identify adolescents at risk&#xD;
      for suicide earlier, which will allow clinicians to prescribe timely treatment and prevent&#xD;
      suicide.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Suicide, the second leading cause of death in adolescents (15-24 year olds), is the most&#xD;
      tragic complication of a psychiatric condition in this age group. Every year, approximately&#xD;
      157,000 youth receive medical care for suicide related injuries at emergency departments&#xD;
      throughout the U.S. Despite some progress, suicide prevention continues to be a daunting&#xD;
      task. In adolescents, the risk of a second suicide attempt is approximately 30% after&#xD;
      discharge from an inpatient psychiatric unit. Up to 80% of suicidal patients who subsequently&#xD;
      died by suicide deny suicidal ideation in their last communication with a health care&#xD;
      provider. Therefore, there is an urgent need for the development of biomarkers that can&#xD;
      objectively identify which youth are most likely to engage in subsequent suicide attempts.&#xD;
&#xD;
      Several lines of evidence (postmortem studies, genetic studies, biomarker studies) as well as&#xD;
      preliminary studies conducted by our group have pointed to neuroinflammation as one of the&#xD;
      neurobiological findings observed in suicidal behavior. In particular, the principal&#xD;
      investigator and co- investigators have identified S100B - an astrocytic protein, which is a&#xD;
      marker of blood brain barrier (BBB) impairment, as a novel biomarker associated with&#xD;
      suicidality in adolescents. We are now also investigating three additional and important&#xD;
      markers Kynurenic Acid (KYNA), Quinolinic Acid (QUIN), and Picolinic Acid (PIC) identified by&#xD;
      Dr. Lena Brundin (Van Andel Institute) to be altered in patients after a suicide attempt.&#xD;
      Other studies have reported several other peripheral inflammatory markers (PlMs) including&#xD;
      interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) as&#xD;
      associated with suicidality. Hence, PlMs either on their own or along with clinical markers&#xD;
      may be particularly useful in predicting future suicide attempts. This study will investigate&#xD;
      whether PIM levels, with or without clinical predictors, can be useful at the time of&#xD;
      discharge from an inpatient psychiatric unit to predict suicidality in adolescent patients in&#xD;
      the subsequent 12 months. The first aim of this study is to determine whether plasma levels&#xD;
      of S100B, IL-1ß, IL-6, TNF-α, KYNA, QUIN, and PIC correlate with suicidal behavior (SB).&#xD;
      Secondly, this study will investigate if any of the PlMs can predict suicidal attempts.&#xD;
      Finally, we will test which combination of clinical risk factors and PlMs is able to most&#xD;
      efficiently predict SB post-discharge from the inpatient unit.&#xD;
&#xD;
      Innovative aspects of this study include: 1) The first study to longitudinally investigate&#xD;
      levels of PlMs at the time of admission and their change at the time of discharge in&#xD;
      adolescent patients being admitted for SB. 2) The first study to investigate whether level of&#xD;
      PIMS (alone or in combination with clinical risk factors) at the time of discharge can&#xD;
      predict readmissions for SB in the next 12 months. 3) Beside the well-studied PIMs in adult&#xD;
      samples, specifically investigate novel biomarkers of inflammation- S100B and 3 markers of&#xD;
      the Kynurenine pathway (KYNA, QUIN and PIC).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2016</start_date>
  <completion_date type="Actual">June 28, 2021</completion_date>
  <primary_completion_date type="Actual">June 28, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Relation between levels of peripheral inflammatory markers and suicide attempt</measure>
    <time_frame>baseline</time_frame>
    <description>Comparison of the levels of peripheral inflammatory markers (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) between participants with and without suicide attempt</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Relation between levels of peripheral inflammatory markers and suicide attempt</measure>
    <time_frame>on the date of discharge from hospital inpatient unit (average length of admission = 5 days)</time_frame>
    <description>Comparison of the levels of peripheral inflammatory markers (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) between participants with and without suicide attempt</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in peripheral inflammatory marker levels for healthy control group</measure>
    <time_frame>baseline and on the date of discharge from hospital inpatient unit (average length of admission = 5 days)</time_frame>
    <description>Comparison of the levels of peripheral inflammatory markers (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) between baseline and discharge time points</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in peripheral inflammatory marker levels for suicide attempt study group</measure>
    <time_frame>baseline and on the date of discharge from hospital inpatient unit (average length of admission = 5 days)</time_frame>
    <description>Comparison of the levels of peripheral inflammatory markers (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) between baseline and discharge time points</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relation between levels of peripheral inflammatory markers and Columbia Suicide Severity Rating Scale scores</measure>
    <time_frame>on the date of discharge from hospital inpatient unit (average length of admission = 5 days)</time_frame>
    <description>Studying relation between inflammatory biomarkers (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) and suicide ideation intensity (scores on Columbia Suicide Severity Rating Scale)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relation between levels of peripheral inflammatory markers and Suicidal Ideation Questionnaire scores</measure>
    <time_frame>on the date of discharge from hospital inpatient unit (average length of admission = 5 days)</time_frame>
    <description>Studying relation between inflammatory biomarkers (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) and suicide ideation intensity (Suicidal Ideation Questionnaire)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relation between levels of peripheral inflammatory markers and depression</measure>
    <time_frame>on the date of discharge from hospital inpatient unit (average length of admission = 5 days)</time_frame>
    <description>Studying relation between inflammatory biomarkers (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) and depression (scores on Children's Depression Rating Scale, Revised)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relation between levels of peripheral inflammatory markers and anxiety</measure>
    <time_frame>on the date of discharge from hospital inpatient unit (average length of admission = 5 days)</time_frame>
    <description>Studying relation between inflammatory biomarkers (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) and anxiety (scores on Multidimensional Anxiety Scale for Children, 2nd Ed)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relation between levels of peripheral inflammatory markers and trauma</measure>
    <time_frame>on the date of discharge from hospital inpatient unit (average length of admission = 5 days)</time_frame>
    <description>Studying relation between inflammatory biomarkers (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) and trauma (scores on Adverse Childhood Experiences Questionnaire (ACE) and Life Events Checklist-5 (LEC-5))</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in peripheral inflammatory marker levels predicting changes in Columbia Suicide Severity Rating Scale scores</measure>
    <time_frame>baseline and on the date of discharge from hospital inpatient unit (average length of admission = 5 days)</time_frame>
    <description>Peripheral inflammatory markers: S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in peripheral inflammatory marker levels predicting changes in Suicidal Ideation Questionnaire scores</measure>
    <time_frame>baseline and on the date of discharge from hospital inpatient unit (average length of admission = 5 days)</time_frame>
    <description>Peripheral inflammatory markers: S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peripheral inflammatory markers as a risk factor for suicide attempts</measure>
    <time_frame>up to 12 months post-discharge</time_frame>
    <description>Studying inflammatory biomarkers (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) as suicide attempt risk factors (frequency of attempts)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peripheral inflammatory markers as a risk factor for suicide ideation intensity (scores on Columbia Suicide Severity Rating Scale)</measure>
    <time_frame>up to 12 months post-discharge</time_frame>
    <description>Studying inflammatory biomarkers (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) as suicide ideation intensity risk factors (scores on Columbia Suicide Severity Rating Scale)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peripheral inflammatory markers as a risk factor for suicide ideation intensity (scores on Suicidal Ideation Questionnaire)</measure>
    <time_frame>up to 12 months post-discharge</time_frame>
    <description>Studying inflammatory biomarkers (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) as suicide ideation intensity risk factors (scores on Suicidal Ideation Questionnaire)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peripheral inflammatory markers as a risk factor for suicide attempt re-admission</measure>
    <time_frame>up to 12 months post-discharge</time_frame>
    <description>Studying inflammatory biomarkers (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) as suicide attempt re-admission risk factors (frequency of re-admissions)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in peripheral inflammatory marker levels from baseline to discharge as a risk factor for suicide attempts</measure>
    <time_frame>up to 12 months post-discharge</time_frame>
    <description>Studying the change in inflammatory biomarkers from baseline to discharge (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) as suicide attempt risk factors (frequency of attempts)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in peripheral inflammatory marker levels from baseline to discharge as a risk factor for suicide ideation intensity (scores on Columbia Suicide Severity Rating Scale)</measure>
    <time_frame>up to 12 months post-discharge</time_frame>
    <description>Studying the change in inflammatory biomarkers from baseline to discharge (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) as suicide ideation intensity risk factors (scores on Columbia Suicide Severity Rating Scale)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in peripheral inflammatory marker levels from baseline to discharge as a risk factor for suicide ideation intensity (scores on Suicidal Ideation Questionnaire)</measure>
    <time_frame>up to 12 months post-discharge</time_frame>
    <description>Studying the change in inflammatory biomarkers from baseline to discharge (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) as suicide ideation intensity risk factors (scores on Suicidal Ideation Questionnaire)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in peripheral inflammatory marker levels from baseline to discharge as a risk factor for suicide attempt re-admission</measure>
    <time_frame>up to 12 months post-discharge</time_frame>
    <description>Studying the change in inflammatory biomarkers from baseline to discharge (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) as suicide attempt re-admission risk factors (frequency of re-admissions)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical assessment values that predict suicide attempts</measure>
    <time_frame>up to 12 months post-discharge</time_frame>
    <description>Studying which clinical assessments can help predict suicide attempt (frequency of attempts)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical assessment values that predict suicide ideation intensity scores on Columbia Suicide Severity Rating Scale</measure>
    <time_frame>up to 12 months post-discharge</time_frame>
    <description>Studying which clinical assessments can help predict suicide ideation intensity scores on Columbia Suicide Severity Rating Scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical assessment values that predict suicide ideation intensity scores on Suicidal Ideation Questionnaire</measure>
    <time_frame>up to 12 months post-discharge</time_frame>
    <description>Studying which clinical assessments can help predict suicide ideation intensity scores on Suicidal Ideation Questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical assessment values that predict suicide attempt re-admission</measure>
    <time_frame>up to 12 months post-discharge</time_frame>
    <description>Studying which clinical assessments can help predict suicide attempt re-admission (frequency of re-admissions)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peripheral inflammatory markers in combination with clinical assessments as predictors for suicide attempts</measure>
    <time_frame>up to 12 months post-discharge</time_frame>
    <description>Studying which combination of inflammatory biomarkers and clinical predictors best predicts future suicide attempts (frequency of attempts)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peripheral inflammatory markers in combination with clinical assessments as predictors for suicide ideation intensity scores on Columbia Suicide Severity Rating Scale</measure>
    <time_frame>up to 12 months post-discharge</time_frame>
    <description>Studying which combination of inflammatory biomarkers and clinical predictors best predicts suicide ideation intensity scores on Columbia Suicide Severity Rating Scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peripheral inflammatory markers in combination with clinical assessments as predictors for suicide ideation intensity scores on Suicidal Ideation Questionnaire</measure>
    <time_frame>up to 12 months post-discharge</time_frame>
    <description>Studying which combination of inflammatory biomarkers and clinical predictors best predicts suicide ideation intensity scores on Suicidal Ideation Questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peripheral inflammatory markers in combination with clinical assessments as predictors for suicide attempt re-admission</measure>
    <time_frame>up to 12 months post-discharge</time_frame>
    <description>Studying which combination of inflammatory biomarkers and clinical predictors best predicts future suicide attempt re-admissions (frequency of re-admissions)</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">80</enrollment>
  <condition>Suicide, Attempted</condition>
  <condition>Suicidal Ideation</condition>
  <condition>Suicidal Intention</condition>
  <condition>Suicide</condition>
  <arm_group>
    <arm_group_label>Suicide Attempt Study Group</arm_group_label>
    <description>Adolescents admitted to the Cleveland Clinic inpatient child and adolescent psychiatry unit after suicide attempt. Clinical assessments and blood samples; follow-up for 12 mos.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy Control Group</arm_group_label>
    <description>Healthy adolescents with no history of suicide attempt. Clinical assessments and blood samples; no 12mo follow-up.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Clinical assessments and blood samples; follow-up for 12 mos</intervention_name>
    <description>Kiddie-Sads Present and Lifetime Version Diagnostic Interview, Columbia-Suicide Severity Rating Scale, Suicidal Ideation Questionnaire, Children's Depression Rating Scale-Revised, Multidimensional Anxiety Scale for Children (2nd Ed), Adverse Childhood Experiences Questionnaire, Life Events Checklist-5, Pubertal Development Scale. All assessments administered at baseline, and a smaller subset of assessments administered at discharge and other time points throughout 12 months follow-up. Blood samples taken at baseline (admission to unit) and day of discharge.</description>
    <arm_group_label>Suicide Attempt Study Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Clinical assessments and blood samples; no 12mo follow-up</intervention_name>
    <description>Kiddie-Sads Present and Lifetime Version Diagnostic Interview, Columbia-Suicide Severity Rating Scale, Suicidal Ideation Questionnaire, Children's Depression Rating Scale-Revised, Multidimensional Anxiety Scale for Children (2nd Ed), Adverse Childhood Experiences Questionnaire, Life Events Checklist-5, Pubertal Development Scale. All assessments administered at baseline, and a smaller subset of assessments administered at discharge time point (5-7 days after baseline). Blood samples taken at baseline and discharge time points (5-7 days after baseline).</description>
    <arm_group_label>Healthy Control Group</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Plasma and serum&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The suicide attempt study group will be recruited from all patients (ages 12-18 years)&#xD;
        admitted to the Cleveland Clinic inpatient child and adolescent psychiatry unit after a&#xD;
        suicide attempt. Healthy adolescent control group (ages 12-18 years) will be recruited&#xD;
        through the Cleveland Clinic pediatric outpatient offices.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Suicide Attempt Study Group:&#xD;
&#xD;
          -  12-18 years of age&#xD;
&#xD;
          -  admitted to the Cleveland Clinic inpatient child and adolescent psychiatry unit after&#xD;
             suicidal ideations or a suicide attempt&#xD;
&#xD;
        Healthy Control Group:&#xD;
&#xD;
          -  12-18 years of age&#xD;
&#xD;
          -  No history of suicide attempt&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Suicide Attempt Study Group:&#xD;
&#xD;
          -  History of autism spectrum disorder&#xD;
&#xD;
          -  Non-verbal&#xD;
&#xD;
          -  Moderate or severe intellectual disability (IQ&lt;70 and patients in special education&#xD;
             full-time)&#xD;
&#xD;
          -  Schizophrenia or schizoaffective disorder diagnosis&#xD;
&#xD;
          -  Current diagnosis of anorexia or bulimia&#xD;
&#xD;
          -  History of generalized tonic-clonic epileptic seizures in last 3 months (If patient&#xD;
             does not have a history of seizures, and generalized tonic-clonic seizure was&#xD;
             clinically determined to be caused by patient's recent overdose attempt, patient can&#xD;
             still be recruited for study if 24 hours has passed since last seizure)&#xD;
&#xD;
          -  History of traumatic brain injury, brain tumor, or any major neurological disorder&#xD;
&#xD;
          -  Delirium or mood disorder secondary to general medical condition&#xD;
&#xD;
          -  Current infection, fever, antibiotic use in the last 2 weeks&#xD;
&#xD;
          -  History of autoimmune or immunodeficiency diseases&#xD;
&#xD;
          -  Current untreated major endocrine disorder&#xD;
&#xD;
          -  Current pregnancy or delivery within the last month&#xD;
&#xD;
          -  Diagnosed malnutrition&#xD;
&#xD;
          -  Positive urine toxicology for benzodiazepines or opiates on admission&#xD;
&#xD;
          -  Current substance use disorder diagnosis and referral for CD assessment upon discharge&#xD;
&#xD;
          -  Current diagnosis of morbid obesity or a current BMI greater than 40 kg/m2&#xD;
&#xD;
          -  Abnormal complete blood count (CBC)&#xD;
&#xD;
        Healthy Control Group:&#xD;
&#xD;
          -  History of any psychiatric diagnosis / treatment (behavioral diagnoses [ADD/ADHD/etc]&#xD;
             are okay)&#xD;
&#xD;
          -  History of suicidal ideation, behavior, or attempt&#xD;
&#xD;
          -  Family history of suicide attempts&#xD;
&#xD;
          -  Diagnosis of schizophrenia or bipolar disorder in parents or siblings&#xD;
&#xD;
          -  History of autism spectrum disorder&#xD;
&#xD;
          -  Moderate or severe intellectual disability (IQ&lt;70 and patients in special education&#xD;
             full-time)&#xD;
&#xD;
          -  History of generalized tonic-clonic epileptic seizures in last 3 months&#xD;
&#xD;
          -  History of headaches or migraines in the last month&#xD;
&#xD;
          -  History of traumatic brain injury, brain tumor, or any major neurological disorder&#xD;
&#xD;
          -  Delirium or mood disorder secondary to general medical condition&#xD;
&#xD;
          -  Current infection, fever, antibiotic use in the last 2 weeks&#xD;
&#xD;
          -  History of autoimmune or immunodeficiency diseases&#xD;
&#xD;
          -  Current untreated major endocrine disorder&#xD;
&#xD;
          -  Current pregnancy or delivery within the last month&#xD;
&#xD;
          -  Diagnosed malnutrition&#xD;
&#xD;
          -  Report of any substance use in week prior&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tatiana Falcone, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Cleveland Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>December 15, 2016</study_first_submitted>
  <study_first_submitted_qc>January 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 9, 2017</study_first_posted>
  <last_update_submitted>July 15, 2021</last_update_submitted>
  <last_update_submitted_qc>July 15, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 16, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Cleveland Clinic</investigator_affiliation>
    <investigator_full_name>Tatiana Falcone, MD</investigator_full_name>
    <investigator_title>Staff, Cleveland Clinic</investigator_title>
  </responsible_party>
  <keyword>Adolescent</keyword>
  <keyword>Biological Markers</keyword>
  <keyword>Biomarkers</keyword>
  <keyword>Biomarkers for suicidality</keyword>
  <keyword>Blood brain barrier</keyword>
  <keyword>Clinical predictors</keyword>
  <keyword>Cytokine</keyword>
  <keyword>Feeling suicidal</keyword>
  <keyword>Inflammation</keyword>
  <keyword>Inflammatory marker</keyword>
  <keyword>Inpatient discharge</keyword>
  <keyword>Interleukin-1 beta</keyword>
  <keyword>IL-1ß</keyword>
  <keyword>Interleukin-6</keyword>
  <keyword>IL-6</keyword>
  <keyword>Kynurenic acid</keyword>
  <keyword>Kynurenine pathway</keyword>
  <keyword>Neuroinflammation</keyword>
  <keyword>Novel marker</keyword>
  <keyword>Peripheral blood biomarkers</keyword>
  <keyword>Picolinic acid</keyword>
  <keyword>Plasma biomarker</keyword>
  <keyword>Psychiatric inpatient</keyword>
  <keyword>S100B</keyword>
  <keyword>Serum biomarker</keyword>
  <keyword>Stress</keyword>
  <keyword>Suicide</keyword>
  <keyword>Suicidal behavior</keyword>
  <keyword>Suicidal risk</keyword>
  <keyword>Tumor necrosis factor alpha</keyword>
  <keyword>TNF-α</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Suicide</mesh_term>
    <mesh_term>Suicidal Ideation</mesh_term>
    <mesh_term>Suicide, Attempted</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03014518
org study id: 16-630
secondary id: MH108857
nct id: NCT03014518
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
Suicide is one of the most devastating events in society at all levels. The primary goal of
      this study is to predict suicide in adolescents at risk. We will utilize blood biomarker
      measurement and clinical risk factor scales to develop a tool to identify adolescents at risk
      for suicide earlier, which will allow clinicians to prescribe timely treatment and prevent
      suicide.
Suicide, the second leading cause of death in adolescents (15-24 year olds), is the most
      tragic complication of a psychiatric condition in this age group. Every year, approximately
      157,000 youth receive medical care for suicide related injuries at emergency departments
      throughout the U.S. Despite some progress, suicide prevention continues to be a daunting
      task. In adolescents, the risk of a second suicide attempt is approximately 30% after
      discharge from an inpatient psychiatric unit. Up to 80% of suicidal patients who subsequently
      died by suicide deny suicidal ideation in their last communication with a health care
      provider. Therefore, there is an urgent need for the development of biomarkers that can
      objectively identify which youth are most likely to engage in subsequent suicide attempts.

      Several lines of evidence (postmortem studies, genetic studies, biomarker studies) as well as
      preliminary studies conducted by our group have pointed to neuroinflammation as one of the
      neurobiological findings observed in suicidal behavior. In particular, the principal
      investigator and co- investigators have identified S100B - an astrocytic protein, which is a
      marker of blood brain barrier (BBB) impairment, as a novel biomarker associated with
      suicidality in adolescents. We are now also investigating three additional and important
      markers Kynurenic Acid (KYNA), Quinolinic Acid (QUIN), and Picolinic Acid (PIC) identified by
      Dr. Lena Brundin (Van Andel Institute) to be altered in patients after a suicide attempt.
      Other studies have reported several other peripheral inflammatory markers (PlMs) including
      interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) as
      associated with suicidality. Hence, PlMs either on their own or along with clinical markers
      may be particularly useful in predicting future suicide attempts. This study will investigate
      whether PIM levels, with or without clinical predictors, can be useful at the time of
      discharge from an inpatient psychiatric unit to predict suicidality in adolescent patients in
      the subsequent 12 months. The first aim of this study is to determine whether plasma levels
      of S100B, IL-1ß, IL-6, TNF-α, KYNA, QUIN, and PIC correlate with suicidal behavior (SB).
      Secondly, this study will investigate if any of the PlMs can predict suicidal attempts.
      Finally, we will test which combination of clinical risk factors and PlMs is able to most
      efficiently predict SB post-discharge from the inpatient unit.

      Innovative aspects of this study include: 1) The first study to longitudinally investigate
      levels of PlMs at the time of admission and their change at the time of discharge in
      adolescent patients being admitted for SB. 2) The first study to investigate whether level of
      PIMS (alone or in combination with clinical risk factors) at the time of discharge can
      predict readmissions for SB in the next 12 months. 3) Beside the well-studied PIMs in adult
      samples, specifically investigate novel biomarkers of inflammation- S100B and 3 markers of
      the Kynurenine pathway (KYNA, QUIN and PIC).
observational model: Case-Control
time perspective: Prospective
measure: Relation between levels of peripheral inflammatory markers and suicide attempt
time frame: baseline
description: Comparison of the levels of peripheral inflammatory markers (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) between participants with and without suicide attempt
measure: Relation between levels of peripheral inflammatory markers and suicide attempt
time frame: on the date of discharge from hospital inpatient unit (average length of admission = 5 days)
description: Comparison of the levels of peripheral inflammatory markers (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) between participants with and without suicide attempt
measure: Change from baseline in peripheral inflammatory marker levels for healthy control group
time frame: baseline and on the date of discharge from hospital inpatient unit (average length of admission = 5 days)
description: Comparison of the levels of peripheral inflammatory markers (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) between baseline and discharge time points
measure: Change from baseline in peripheral inflammatory marker levels for suicide attempt study group
time frame: baseline and on the date of discharge from hospital inpatient unit (average length of admission = 5 days)
description: Comparison of the levels of peripheral inflammatory markers (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) between baseline and discharge time points
measure: Relation between levels of peripheral inflammatory markers and Columbia Suicide Severity Rating Scale scores
time frame: on the date of discharge from hospital inpatient unit (average length of admission = 5 days)
description: Studying relation between inflammatory biomarkers (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) and suicide ideation intensity (scores on Columbia Suicide Severity Rating Scale)
measure: Relation between levels of peripheral inflammatory markers and Suicidal Ideation Questionnaire scores
time frame: on the date of discharge from hospital inpatient unit (average length of admission = 5 days)
description: Studying relation between inflammatory biomarkers (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) and suicide ideation intensity (Suicidal Ideation Questionnaire)
measure: Relation between levels of peripheral inflammatory markers and depression
time frame: on the date of discharge from hospital inpatient unit (average length of admission = 5 days)
description: Studying relation between inflammatory biomarkers (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) and depression (scores on Children's Depression Rating Scale, Revised)
measure: Relation between levels of peripheral inflammatory markers and anxiety
time frame: on the date of discharge from hospital inpatient unit (average length of admission = 5 days)
description: Studying relation between inflammatory biomarkers (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) and anxiety (scores on Multidimensional Anxiety Scale for Children, 2nd Ed)
measure: Relation between levels of peripheral inflammatory markers and trauma
time frame: on the date of discharge from hospital inpatient unit (average length of admission = 5 days)
description: Studying relation between inflammatory biomarkers (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) and trauma (scores on Adverse Childhood Experiences Questionnaire (ACE) and Life Events Checklist-5 (LEC-5))
measure: Changes in peripheral inflammatory marker levels predicting changes in Columbia Suicide Severity Rating Scale scores
time frame: baseline and on the date of discharge from hospital inpatient unit (average length of admission = 5 days)
description: Peripheral inflammatory markers: S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid
measure: Changes in peripheral inflammatory marker levels predicting changes in Suicidal Ideation Questionnaire scores
time frame: baseline and on the date of discharge from hospital inpatient unit (average length of admission = 5 days)
description: Peripheral inflammatory markers: S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid
measure: Peripheral inflammatory markers as a risk factor for suicide attempts
time frame: up to 12 months post-discharge
description: Studying inflammatory biomarkers (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) as suicide attempt risk factors (frequency of attempts)
measure: Peripheral inflammatory markers as a risk factor for suicide ideation intensity (scores on Columbia Suicide Severity Rating Scale)
time frame: up to 12 months post-discharge
description: Studying inflammatory biomarkers (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) as suicide ideation intensity risk factors (scores on Columbia Suicide Severity Rating Scale)
measure: Peripheral inflammatory markers as a risk factor for suicide ideation intensity (scores on Suicidal Ideation Questionnaire)
time frame: up to 12 months post-discharge
description: Studying inflammatory biomarkers (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) as suicide ideation intensity risk factors (scores on Suicidal Ideation Questionnaire)
measure: Peripheral inflammatory markers as a risk factor for suicide attempt re-admission
time frame: up to 12 months post-discharge
description: Studying inflammatory biomarkers (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) as suicide attempt re-admission risk factors (frequency of re-admissions)
measure: Change in peripheral inflammatory marker levels from baseline to discharge as a risk factor for suicide attempts
time frame: up to 12 months post-discharge
description: Studying the change in inflammatory biomarkers from baseline to discharge (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) as suicide attempt risk factors (frequency of attempts)
measure: Change in peripheral inflammatory marker levels from baseline to discharge as a risk factor for suicide ideation intensity (scores on Columbia Suicide Severity Rating Scale)
time frame: up to 12 months post-discharge
description: Studying the change in inflammatory biomarkers from baseline to discharge (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) as suicide ideation intensity risk factors (scores on Columbia Suicide Severity Rating Scale)
measure: Change in peripheral inflammatory marker levels from baseline to discharge as a risk factor for suicide ideation intensity (scores on Suicidal Ideation Questionnaire)
time frame: up to 12 months post-discharge
description: Studying the change in inflammatory biomarkers from baseline to discharge (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) as suicide ideation intensity risk factors (scores on Suicidal Ideation Questionnaire)
measure: Change in peripheral inflammatory marker levels from baseline to discharge as a risk factor for suicide attempt re-admission
time frame: up to 12 months post-discharge
description: Studying the change in inflammatory biomarkers from baseline to discharge (S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid) as suicide attempt re-admission risk factors (frequency of re-admissions)
measure: Clinical assessment values that predict suicide attempts
time frame: up to 12 months post-discharge
description: Studying which clinical assessments can help predict suicide attempt (frequency of attempts)
measure: Clinical assessment values that predict suicide ideation intensity scores on Columbia Suicide Severity Rating Scale
time frame: up to 12 months post-discharge
description: Studying which clinical assessments can help predict suicide ideation intensity scores on Columbia Suicide Severity Rating Scale
measure: Clinical assessment values that predict suicide ideation intensity scores on Suicidal Ideation Questionnaire
time frame: up to 12 months post-discharge
description: Studying which clinical assessments can help predict suicide ideation intensity scores on Suicidal Ideation Questionnaire
measure: Clinical assessment values that predict suicide attempt re-admission
time frame: up to 12 months post-discharge
description: Studying which clinical assessments can help predict suicide attempt re-admission (frequency of re-admissions)
measure: Peripheral inflammatory markers in combination with clinical assessments as predictors for suicide attempts
time frame: up to 12 months post-discharge
description: Studying which combination of inflammatory biomarkers and clinical predictors best predicts future suicide attempts (frequency of attempts)
measure: Peripheral inflammatory markers in combination with clinical assessments as predictors for suicide ideation intensity scores on Columbia Suicide Severity Rating Scale
time frame: up to 12 months post-discharge
description: Studying which combination of inflammatory biomarkers and clinical predictors best predicts suicide ideation intensity scores on Columbia Suicide Severity Rating Scale
measure: Peripheral inflammatory markers in combination with clinical assessments as predictors for suicide ideation intensity scores on Suicidal Ideation Questionnaire
time frame: up to 12 months post-discharge
description: Studying which combination of inflammatory biomarkers and clinical predictors best predicts suicide ideation intensity scores on Suicidal Ideation Questionnaire
measure: Peripheral inflammatory markers in combination with clinical assessments as predictors for suicide attempt re-admission
time frame: up to 12 months post-discharge
description: Studying which combination of inflammatory biomarkers and clinical predictors best predicts future suicide attempt re-admissions (frequency of re-admissions)
arm group label: Suicide Attempt Study Group
description: Adolescents admitted to the Cleveland Clinic inpatient child and adolescent psychiatry unit after suicide attempt. Clinical assessments and blood samples; follow-up for 12 mos.
arm group label: Healthy Control Group
description: Healthy adolescents with no history of suicide attempt. Clinical assessments and blood samples; no 12mo follow-up.
intervention type: Other
intervention name: Clinical assessments and blood samples; follow-up for 12 mos
description: Kiddie-Sads Present and Lifetime Version Diagnostic Interview, Columbia-Suicide Severity Rating Scale, Suicidal Ideation Questionnaire, Children's Depression Rating Scale-Revised, Multidimensional Anxiety Scale for Children (2nd Ed), Adverse Childhood Experiences Questionnaire, Life Events Checklist-5, Pubertal Development Scale. All assessments administered at baseline, and a smaller subset of assessments administered at discharge and other time points throughout 12 months follow-up. Blood samples taken at baseline (admission to unit) and day of discharge.
arm group label: Suicide Attempt Study Group
intervention type: Other
intervention name: Clinical assessments and blood samples; no 12mo follow-up
description: Kiddie-Sads Present and Lifetime Version Diagnostic Interview, Columbia-Suicide Severity Rating Scale, Suicidal Ideation Questionnaire, Children's Depression Rating Scale-Revised, Multidimensional Anxiety Scale for Children (2nd Ed), Adverse Childhood Experiences Questionnaire, Life Events Checklist-5, Pubertal Development Scale. All assessments administered at baseline, and a smaller subset of assessments administered at discharge time point (5-7 days after baseline). Blood samples taken at baseline and discharge time points (5-7 days after baseline).
arm group label: Healthy Control Group
Plasma and serum
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 12 Years
maximum age: 18 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Tatiana Falcone, M.D.
role: Principal Investigator
affiliation: The Cleveland Clinic
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: The Cleveland Clinic
investigator full name: Tatiana Falcone, MD
investigator title: Staff, Cleveland Clinic
mesh term: Suicide
mesh term: Suicidal Ideation
mesh term: Suicide, Attempted
sharing ipd: No