Symptoms and General Pathology

All Conditions

Behaviors and Mental Disorders

Inflammation

Suicidal Ideation

Necrosis

Suicide

Suicide, Attempted

Self-Injurious Behavior

Behavioral Symptoms

All Drugs and Chemicals

Picolinic acid

Kynurenic Acid

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.

Healthy adolescents with no history of suicide attempt. Clinical assessments and blood samples; no 12mo follow-up.

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.

Clinical assessments and blood samples; follow-up for 12 mos

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).

Clinical assessments and blood samples; no 12mo follow-up

Tatiana Falcone, M.D.

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).

Biomarkers as Predictors of Suicidal Risk in Adolescents

Peripheral Neuroinflammatory Predictors of Suicidal Risk at Time of Inpatient Discharge in Adolescents

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

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

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)

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)

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)

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)

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))

Peripheral inflammatory markers: S100B, IL-6, IL-1β, TNF-α, kynurenic acid, quinolinic acid, and picolinic acid

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)

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)

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)

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)

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)

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)

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)

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)

Studying which clinical assessments can help predict suicide attempt (frequency of attempts)

Studying which clinical assessments can help predict suicide ideation intensity scores on Columbia Suicide Severity Rating Scale

Studying which clinical assessments can help predict suicide ideation intensity scores on Suicidal Ideation Questionnaire

Studying which clinical assessments can help predict suicide attempt re-admission (frequency of re-admissions)

Studying which combination of inflammatory biomarkers and clinical predictors best predicts future suicide attempts (frequency of attempts)

Studying which combination of inflammatory biomarkers and clinical predictors best predicts suicide ideation intensity scores on Columbia Suicide Severity Rating Scale

Studying which combination of inflammatory biomarkers and clinical predictors best predicts suicide ideation intensity scores on Suicidal Ideation Questionnaire

Studying which combination of inflammatory biomarkers and clinical predictors best predicts future suicide attempt re-admissions (frequency of re-admissions)

Case Western Reserve University

Van Andel Research Institute

National Institute of Mental Health (NIMH)

The Cleveland Clinic

Staff, Cleveland Clinic

Ambulatory cancer population already seeking psychosocial support.

All data gathered will be quantitative in nature. In addition to participant completed surveys, additional demographic, and diagnosis/treatment related information will be collected from the patient's electronic medical record via Health Data Compass. Subsequent data collected as part of the patient's standard psychosocial and cancer related care (i.e., health outcomes, future utilization of UCCC psychosocial services) will also be gathered. This subsequent data collection will not include further participation, but continued access to the patient's medical record. Protected health information collected for this project will include dates (e.g., birth dates, date of diagnosis, date since last treatment, death dates) and participant zip codes. No other identifiable data will be collected. A separate survey emailed to the participant at the end of the study will collect information regarding the participant's completion status of the survey.

Survey

The goal of this project is to assess the feasibility of collecting physiological and psychological data that will allow for preliminary investigation of predictors of suicidal ideation in an ambulatory cancer population already seeking psychosocial support.

Exploratory analyses will be the first step to establishing possible predictive relationships. The long-term goal of this research is to identifying an integrated model of suicidal ideation in cancer, so that providers will be better able to identify appropriate screening methods to target patients at high risk for suicide. This information will ultimately inform the development of psychosocial interventions that specifically address the variables that increase suicide risk in patients with cancer.

Improving Our Understanding of Suicidal Ideation in Cancer Survivors

Analyses will be stratified by cancer survivors with and without suicidal ideation. Descriptive statistics will be reported for clinical, demographic, and other study variables. Depending on data type and distribution, means, medians, or proportions will be reported with appropriate measures of data spread (i.e., standard deviation, range). Univariate analyses using the appropriate statistical tests (i.e., independent t-test, Wilcoxon rank sum, chi-square, logistic regression) will be performed to compare the two study groups. To allow for adjustment of potential confounders, multivariate analyses will be done using logistic regression techniques. Odds ratios and 95% confidence intervals will be reported. All tests will be two-sided and alpha will be set at 0.05. Data analyses and graphic results will be done using SAS (ver 9.4, SAS Institute, Cary, NC) and GraphPad Prism (ver 7.01, GraphPad Software Inc, La Jolla, CA).

To evaluate the feasibility of data collection regarding physiological and psychological factors influencing suicidal ideation in cancer survivors

The Brief Pain Inventory (BPI; Cleeland \& Ryan, 1994) Pain Severity Scale consists of four 0-10 numerical rating scales evaluating (1) current pain as well as (2) worst (3) least and (4) average pain during the past 7 days. For this rating scale zero indicates, "no pain" while 10 indicates, "pain as bad as you can imagine". Averaging these four scores creates a composite score for pain severity. The measures has shown good internal consistency with Cronbach's alphas ranging from .78-.97 (Jensen, 2003).

The BPI's Pain Interference Scale (Cleeland \& Ryan, 1994) consists of seven items reflecting daily activities, including general activity, mood, walking ability, work, relationships, sleep, and enjoyment of life. A 0-10 numerical rating scale indicates the level of interference pain has had on each activity, with zero indicating, "does not interfere" and 10 indicating, "completely interferes". Averaging these seven scores creates a composite score for pain interference. The measure has shown good internal consistency with Cronbach's alphas ranging from .78-.91 (Jensen, 2003).

The MD Anderson Symptom Inventory (MDASI; Cleeland et al, 2000) is a self-report measure of cancer treatment-related symptoms. The measure includes 19 items, 13 of which comprise the symptom severity subscale and 6 of which comprise the symptom interference subscale. The symptom severity subscale asks patients to rate how severe various cancer-related symptoms (e.g., lack of appetite, dry mouth, fatigue) have been for them in the past 24 hours. Items on the symptom severity subscale are rated on a 0-10 numeric rating scale where 0 indicates "not present" and 10 indicates "as bad as you can imagine". The symptom interference subscale asks patients to rate the extent to which their symptoms have interfered with various domains of functioning (e.g. walking, enjoyment of life) in the past 24 hours. Items on the symptom interference subscale are rated on a 0-10 numeric rating scale where 0 indicates "did not interfere" and 10 indicates "interfered completely".

The PROMIS physical function short-form 6b (PF 6b) is a six item measure evaluating physical function using items from the National Institute of Health's Patient-Reported Outcomes Measurement Information System. Items on the PF 6b include questions such as "Does your health now limit you in doing two hours of physical labor?" and "Are you able to go up and down stairs at a normal pace?. Item responses are made on a 5-point Likert scale with one indicating "unable to do" and five indicating "without any difficulty". The measure has good internal reliability with a Cronbach's alpha of 0.94 (Jensen et al, 2015)

The Functional Assessment of Cancer Therapy Scale-General (FACT-G; Cella et al, 1993) is a 27-item self-report measure of general cancer quality of life which includes physical, functional, social, and emotional well-being subscales. Items evaluate the endorsement of various cancer related symptoms, treatment related difficulties, or facets of psychosocial functioning within the past week. Item responses are rated on a 5-point Likert scale with zero indicating "not at all" and four indicating "very much". The measure has good internal reliability with a Cronbach's alpha of .89 (Cella et al, 1993).

The Suicidal Behaviors Questionnaire-Revised (SBQ-R; Osman et al, 2001) consists of four items which each tap into a different dimension of suicidality. Item 1 taps into lifetime suicidal ideation and/or suicide attempt. Item 2 assesses the frequency of suicidal ideation over the past twelve months. Item 3 assesses the threat of suicide attempt. Item 4 evaluates self-reported likelihood of suicidal behavior in the future. In adult general populations, this measure demonstrated 93% sensitivity and 95% specificity (Osman et al, 2001).

The Acceptance and Action Questionnaire-II (Bond et al, 2011) is a 7 item self-report measure assessing experiential avoidance. Item responses are rated on a seven-point Likert scale indicating the degree to which each statement is true for them ranging from (1) never true to (7) always true. The scale is scored by summing the seven items, with higher scores indicating lower levels of experiential acceptance. The measure has shown good internal reliability with a Cronbach's alpha of .84 (Bond et al, 2011).

The Patient Health Questionnaire (PHQ-9; Kroenke, Spitzer, \& Williams, 2001) is a nine item self-report measure assessing the presence of DSM-IV criteria for major depressive episodes in the past two-week period. Item responses are rated on a four-point Likert scale with zero indicating "not at all" and three indicating "nearly every day". It has good internal reliability, with a Cronbach's alpha of 0.89 in primary care populations (Kroenke et al, 2001), and is endorsed by the American Society of Clinical Oncology (ASCO; Andersen et al, 2014) as a recommended screening tool for depression in cancer patients.

The Hopelessness Assessment in Illness Questionnaire (Rosenfeld et al, 2011) is an eight item measure designed specifically to assess the construct of hopelessness as it pertains to terminally ill patients as it assesses hopelessness rather than awareness of prognosis. It is also shorter than other commonly used measures of hopelessness resulting in reduced patient burden. Each item has a three-choice anchored response format. The HAI has good internal reliability, with a Cronbach's alpha of 0.87. It demonstrated utility in predicting important psychosocial outcomes in terminally ill patients including suicidal ideation and desire for hastened death. It is recommended for use in other medically ill populations as well as terminally ill populations.

The GAD-7 (Spitzer, Kroenke, Williams \& Lowe, 2006) is a seven-item self- report measure evaluating symptoms of anxiety associated with Generalized Anxiety Disorder experienced over the past two weeks. Items are rated on a 4-point Likert scale with zero indicating "not at all" and three indicating "nearly every day". It has good internal reliability, with a Cronbach's alpha of 0.92 (Spitzer et al. 2006), and is endorsed by ASCO as a recommended screening tool for anxiety in cancer patients (Andersen et al, 2014).

The Demoralization Scale-II (DS-II; Robinson et al., 2016a) is a sixteen-item scale that consists of two eight item subscales, meaning and purpose and distress and coping ability. A subtest analysis supported the use of a total score to estimate the construct of demoralization. Each item contains three response options (never, sometimes, and often). The DS-II has good internal consistence, as Cronbach's alpha for the total scale is .89. The scale demonstrated convergent validity with measures of quality of life and psychological distress in patients receiving palliative care (Robinson et al., 2016b).

The Schedule of Attitudes Toward Hastened Death-Abbreviated (SAHD-A; Kolva, Rosenfeld, Liu, Pessin, Breitbart, 2016) is a six item measure self-report measure evaluating the desire for hastened death. The SAHD-A is short form of the Schedule of Attitudes toward Hastened Death (SAHD; Rosenfeld et al., 1999) the most commonly used self-report measure of desire for hastened death. The SAHD-A uses a True/False format and is comparable to the SAHD-A in its relationship to measures of psychological distress (i.e., depression, hopelessness, suicidal ideation), has good internal consistency (Cronbach's alpha = .83), and its short form reduces patient burden.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Biomarkers as Predictors of Suicidal Risk in Adolescents	NCT03014518	Suicide, Attemp... Suicidal Ideati... Suicidal Intent... Suicide	Clinical assess... Clinical assess...	12 Years - 18 Years	The Cleveland Clinic
Improving Our Understanding of Suicidal Ideation in Cancer Survivors	NCT04866758	Suicidal Ideati...	Survey	18 Years - 100 Years	University of Colorado, Denver
Improving Our Understanding of Suicidal Ideation in Cancer Survivors	NCT04866758	Suicidal Ideati...	Survey	18 Years - 100 Years	University of Colorado, Denver

Spots Global Cancer Trial Database for suicidal ideation