Biomarkers as Predictors of Suicidal Risk in Adolescents

NCT ID: NCT03014518

Last Updated: 2021-07-16

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 80 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-12-31
• Study Completion Date: 2021-06-28

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).

Conditions

Suicide, Attempted; Suicidal Ideation; Suicidal Intention; Suicide

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Suicide Attempt Study Group

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.

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

Intervention Type: OTHER

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.

Healthy Control Group

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

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

Intervention Type: OTHER

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).

Interventions

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 and other time points throughout 12 months follow-up. Blood samples taken at baseline (admission to unit) and day of discharge.

Intervention Type: OTHER

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 time point (5-7 days after baseline). Blood samples taken at baseline and discharge time points (5-7 days after baseline).

Intervention Type: OTHER

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

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Case Western Reserve University

OTHER

Sponsor Role: collaborator

Van Andel Research Institute

OTHER

Sponsor Role: collaborator

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

The Cleveland Clinic

OTHER

Sponsor Role: lead

Responsible Party

Tatiana Falcone, MD

Staff, Cleveland Clinic

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Tatiana Falcone, M.D.

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Locations

The Cleveland Clinic

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

MH108857

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

16-630

Identifier Type: -

Identifier Source: org_study_id