Clinical trial NCT03014518: Biomarkers as Predictors of Suicidal Risk in Adolescents
Official title: Peripheral Neuroinflammatory Predictors of Suicidal Risk at Time of Inpatient Discharge in Adolescents
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Suicide, Attempted
Suicidal Ideation
Suicidal Intention
Suicide
Keywords: Adolescent
Biological Markers
Biomarkers
Biomarkers for suicidality
Blood brain barrier
Clinical predictors
Cytokine
Feeling suicidal
Inflammation
Inflammatory marker
Inpatient discharge
Interleukin-1 beta
IL-1ß
Interleukin-6
IL-6
Kynurenic acid
Kynurenine pathway
Neuroinflammation
Novel marker
Peripheral blood biomarkers
Picolinic acid
Plasma biomarker
Psychiatric inpatient
S100B
Serum biomarker
Stress
Suicide
Suicidal behavior
Suicidal risk
Tumor necrosis factor alpha
TNF-α
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
Collaborators: name: Case Western Reserve University
name: Van Andel Research Institute
name: National Institute of Mental Health (NIMH)
First posted: 2017-01-09
Enrollment: 80
Sex: ALL
Minimum age (years): 12
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The suicide attempt study group will be recruited from all patients (ages 12-18 years) admitted to the Cleveland Clinic inpatient child and adolescent psychiatry unit after a suicide attempt. Healthy adolescent control group (ages 12-18 years) will be recruited through the Cleveland Clinic pediatric outpatient offices.

Brief summary: 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.

Detailed description: 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).

Eligibility criteria: Inclusion Criteria:

Suicide Attempt Study Group:

* 12-18 years of age
* admitted to the Cleveland Clinic inpatient child and adolescent psychiatry unit after suicidal ideations or a suicide attempt

Healthy Control Group:

* 12-18 years of age
* No history of suicide attempt

Exclusion Criteria:

Suicide Attempt Study Group:

* History of autism spectrum disorder
* Non-verbal
* Moderate or severe intellectual disability (IQ\<70 and patients in special education full-time)
* Schizophrenia or schizoaffective disorder diagnosis
* Current diagnosis of anorexia or bulimia
* History of generalized tonic-clonic epileptic seizures in last 3 months (If patient does not have a history of seizures, and generalized tonic-clonic seizure was clinically determined to be caused by patient's recent overdose attempt, patient can still be recruited for study if 24 hours has passed since last seizure)
* History of traumatic brain injury, brain tumor, or any major neurological disorder
* Delirium or mood disorder secondary to general medical condition
* Current infection, fever, antibiotic use in the last 2 weeks
* History of autoimmune or immunodeficiency diseases
* Current untreated major endocrine disorder
* Current pregnancy or delivery within the last month
* Diagnosed malnutrition
* Positive urine toxicology for benzodiazepines or opiates on admission
* Current substance use disorder diagnosis and referral for CD assessment upon discharge
* Current diagnosis of morbid obesity or a current BMI greater than 40 kg/m2
* Abnormal complete blood count (CBC)

Healthy Control Group:

* History of any psychiatric diagnosis / treatment (behavioral diagnoses \[ADD/ADHD/etc\] are okay)
* History of suicidal ideation, behavior, or attempt
* Family history of suicide attempts
* Diagnosis of schizophrenia or bipolar disorder in parents or siblings
* History of autism spectrum disorder
* Moderate or severe intellectual disability (IQ\<70 and patients in special education full-time)
* History of generalized tonic-clonic epileptic seizures in last 3 months
* History of headaches or migraines in the last month
* History of traumatic brain injury, brain tumor, or any major neurological disorder
* Delirium or mood disorder secondary to general medical condition
* Current infection, fever, antibiotic use in the last 2 weeks
* History of autoimmune or immunodeficiency diseases
* Current untreated major endocrine disorder
* Current pregnancy or delivery within the last month
* Diagnosed malnutrition
* Report of any substance use in week prior

Primary outcomes:
measure: Relation between levels of peripheral inflammatory markers and suicide attempt
timeFrame: baseline
measure: Relation between levels of peripheral inflammatory markers and suicide attempt
timeFrame: on the date of discharge from hospital inpatient unit (average length of admission = 5 days)
Secondary outcomes:
measure: Change from baseline in peripheral inflammatory marker levels for healthy control group
timeFrame: baseline and on the date of discharge from hospital inpatient unit (average length of admission = 5 days)
measure: Change from baseline in peripheral inflammatory marker levels for suicide attempt study group
timeFrame: baseline and on the date of discharge from hospital inpatient unit (average length of admission = 5 days)
measure: Relation between levels of peripheral inflammatory markers and Columbia Suicide Severity Rating Scale scores
timeFrame: on the date of discharge from hospital inpatient unit (average length of admission = 5 days)
measure: Relation between levels of peripheral inflammatory markers and Suicidal Ideation Questionnaire scores
timeFrame: on the date of discharge from hospital inpatient unit (average length of admission = 5 days)
measure: Relation between levels of peripheral inflammatory markers and depression
timeFrame: on the date of discharge from hospital inpatient unit (average length of admission = 5 days)
measure: Relation between levels of peripheral inflammatory markers and anxiety
timeFrame: on the date of discharge from hospital inpatient unit (average length of admission = 5 days)
measure: Relation between levels of peripheral inflammatory markers and trauma
timeFrame: on the date of discharge from hospital inpatient unit (average length of admission = 5 days)
measure: Changes in peripheral inflammatory marker levels predicting changes in Columbia Suicide Severity Rating Scale scores
timeFrame: baseline and on the date of discharge from hospital inpatient unit (average length of admission = 5 days)
measure: Changes in peripheral inflammatory marker levels predicting changes in Suicidal Ideation Questionnaire scores
timeFrame: baseline and on the date of discharge from hospital inpatient unit (average length of admission = 5 days)
measure: Peripheral inflammatory markers as a risk factor for suicide attempts
timeFrame: up to 12 months post-discharge
measure: Peripheral inflammatory markers as a risk factor for suicide ideation intensity (scores on Columbia Suicide Severity Rating Scale)
timeFrame: up to 12 months post-discharge
measure: Peripheral inflammatory markers as a risk factor for suicide ideation intensity (scores on Suicidal Ideation Questionnaire)
timeFrame: up to 12 months post-discharge
measure: Peripheral inflammatory markers as a risk factor for suicide attempt re-admission
timeFrame: up to 12 months post-discharge
measure: Change in peripheral inflammatory marker levels from baseline to discharge as a risk factor for suicide attempts
timeFrame: up to 12 months post-discharge
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)
timeFrame: up to 12 months post-discharge
measure: Change in peripheral inflammatory marker levels from baseline to discharge as a risk factor for suicide ideation intensity (scores on Suicidal Ideation Questionnaire)
timeFrame: up to 12 months post-discharge
measure: Change in peripheral inflammatory marker levels from baseline to discharge as a risk factor for suicide attempt re-admission
timeFrame: up to 12 months post-discharge
measure: Clinical assessment values that predict suicide attempts
timeFrame: up to 12 months post-discharge
measure: Clinical assessment values that predict suicide ideation intensity scores on Columbia Suicide Severity Rating Scale
timeFrame: up to 12 months post-discharge
measure: Clinical assessment values that predict suicide ideation intensity scores on Suicidal Ideation Questionnaire
timeFrame: up to 12 months post-discharge
measure: Clinical assessment values that predict suicide attempt re-admission
timeFrame: up to 12 months post-discharge
measure: Peripheral inflammatory markers in combination with clinical assessments as predictors for suicide attempts
timeFrame: up to 12 months post-discharge
measure: Peripheral inflammatory markers in combination with clinical assessments as predictors for suicide ideation intensity scores on Columbia Suicide Severity Rating Scale
timeFrame: up to 12 months post-discharge
measure: Peripheral inflammatory markers in combination with clinical assessments as predictors for suicide ideation intensity scores on Suicidal Ideation Questionnaire
timeFrame: up to 12 months post-discharge
measure: Peripheral inflammatory markers in combination with clinical assessments as predictors for suicide attempt re-admission
timeFrame: up to 12 months post-discharge
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: The Cleveland Clinic
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Tatiana Falcone, M.D.
role: PRINCIPAL_INVESTIGATOR
References: