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

Neoplasms

Nervous System Diseases

Hypoxia

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Signs and Symptoms, Respiratory

Central Nervous System Depressants

Analgesics

Pharmaceutical Solutions

Anesthetics

Dexmedetomidine

Hypnotics and Sedatives

Analgesics, Non-Narcotic

Adrenergic Agents

Adrenergic alpha-Agonists

Adrenergic Agonists

Neurotransmitter Agents

Dexmedetomidine 2 μg/ml will be given as bolus 1mg/kg for 10 minutes with a maintenance dose of 0.8μg/kg/h until surgery completion

Normal saline (NaCl 0.9%) administration will start 10 minutes after anesthesia induction and maintained throughout the surgical procedure.

Equivalent doses for a solution containing 2mcg/ml of the tested drug calculating for a bolus 1mg/kg for 10 minutes with a maintenance dose of 0.8μg/kg/h until surgery completion

Normal saline

Georgia Tsaousi, Professor

Brain tumor surgery is commonly associated with different degrees of preoperative intracranial hypertension and surrounding tumor edema, elicited by tumor underlying pathophysiology. During craniotomy for brain tumor resection maintenance of hemodynamic stability and intracranial homoeostasis is of paramount importance. Disordered hemodynamics or adverse stress may activate the immune inflammation or neuroendocrine responses and lead to a surge of inflammatory mediators and stress hormones, which are implicated in secondary brain insults.

Adverse physiological responses caused by intraoperative disordered hemodynamics or surgery-related damage, may lead to some secondary brain injury (such as cerebral edema or cerebral hemorrhage), aggravating damage to brain tissue and affecting the recovery from anesthesia, cognition and prognosis in patients.

Prevention of secondary brain injury is a key-endpoint to improve clinical outcomes in glioma patients undergoing craniotomy.

Alpha2-adrenoceptor agonists have been widely used for sedation, analgesia and anti-sympathetic actions for many years, but the definite evidence of their potential use as neuroprotectants has so far been confined to animal studies, yet the findings are inconsistent.

Dexmedetomidine (DEX) has been demonstrated to be a new type a2 adrenergic receptor (a2-AR) agonist, which can selectively bind with the a1 and a2 adrenergic receptor, and playing a dual role by restraining the activity of sympathetic nervous and stimulating the vagus nerve. Dexmedetomidine (DEX) also plays an important role in in inhibiting inflammatory and neuroendocrine responses. Animal experiments showed that the right must have a dexmedetomidine neuro-protective effect. However, the brain-protective effect of dexmedetomidine in anesthesia of craniotomy resection of glioma has not been reported.

Thus, the aim of this study was to explore the effect of dexmedetomidine on perioperative brain protection, as well as cerebral oxygenation and metabolic status aiming to provide a basis for clinical rational drug use in patients undergoing craniotomy resection of glioma.

Each participant will receive standard monitoring (ECG, SpO2, SBP, BIS, urine output, temperature). More detailed hemodynamic monitoring will be obtained by Edwards Lifesciences ClearSight system (CO, CI, SV, SVI, SVV, SVR, SVRI).

TCI Propofol and Remifentanil will be the agents of choice for induction and maintenance in anesthesia and cisatracurium will be used for neuromuscular blockade for intubation.

Protective mechanical ventilation will be chosen (7ml/kg IBW) with a respiratory rate to obtain a PaCO2 of 35-40 mmHg. PEEP will be changed for the best PaO2/FiO2 ratio and FiO2 of choice will be 0.5.

The radial artery catheterization will be applied for direct blood pressure measurement and arterial blood gas sampling (pH, PaO2, PaCO2, HCO3, BE, osmolality, lactic acid, Hb, glucose, Na and K will be measured).

The jugular bulb ipsilateral to the craniotomy site will be catheterized for receiving blood samples for blood gas analysis. The following oxygenation and metabolic parameters / derivates will be measured or calculated: SjvO2, pH, PjvO2, PjvCO2, HCO3, BE, Osmolality, Lactic acid jv, Hb, Glucose, Na, K, AjvDO2, AjvCO2, O2ERbr, eRQbr, AjvDL, and LOI.

Dexmedetomidine or normal saline (placebo) administration will start 10 minutes after anesthesia induction and maintained throughout the surgical procedure.

Phases

* T0: 5 minutes before administration of either DEX or placebo
* T15: 10 minutes after administration of either DEX or placebo
* T30: 30 minutes after administration of either DEX or placebo
* T60: 60 minutes after administration of either DEX or placebo
* T120: 120 minutes after administration of either DEX or placebo
* T240: 240 minutes after administration of either DEX or placebo
* End of surgical procedure Blood samples for measuring S-100b, NSE, cortisol, TNF-a and IL-6 will be obtained at phases T0, end of surgery and 24 hours after administration of either DEX or placebo.

Neurocognitive testing will be performed before surgery, 1 week and 1 month later using Karnofsky Performance Status (KFS), Mini Mental State Exam (MMSE), Μontreal Cognitive Assessment (MoCA) and Addenbrooke's Cognitive Exam (ACE III).

Intraoperative consumption of propofol and remifentanil will also be recorded

Effect of Dexmedetomidine on Brain Homeostasis and Neurocognitive Outcome

Effect of Dexmedetomidine on Brain Homeostasis and Neurocognitive Outcome of Patients Undergoing Brain Tumor Exclusion

Alterations in jugular venous oxygen saturation (%), after intravenous infusion of equivalent doses of dexmedetomidine or placebo (normal saline)

Alterations in arterio-jugular oxygen difference (AjvDO2 \[ml/dl\]), after intravenous infusion of equivalent doses of dexmedetomidine or placebo (normal saline)

Alterations in arterio-jugular carbon dioxide difference (AjvCO2 \[mmHg\]), after intravenous infusion of equivalent doses of dexmedetomidine or placebo (normal saline)

Alterations in brain oxygen extraction ratio (O2Erbr \[%\]), after intravenous infusion of equivalent doses of dexmedetomidine or placebo (normal saline)

Alterations in S-100b (μg/L) after intravenous infusion of equivalent doses of dexmedetomidine or placebo (normal saline)

Alterations in NSE (ng/ml) after intravenous infusion of equivalent doses of dexmedetomidine or placebo (normal saline)

Alterations in serum cortisol (μg/dl) levels after intravenous infusion of equivalent doses of dexmedetomidine or placebo (normal saline)

Alterations in serum TNF-a (pg/ml) levels after intravenous infusion of equivalent doses of dexmedetomidine or placebo (normal saline)

Alterations in serum IL-6 (pg/ml) levels after intravenous infusion of equivalent doses of dexmedetomidine or placebo (normal saline)

Alterations in Mini-Mental State Exam (MMSE) after intravenous infusion of equivalent doses of dexmedetomidine or placebo (normal saline)

Alterations in Μontreal Cognitive Assessment (MoCA) after intravenous infusion of equivalent doses of dexmedetomidine or placebo (normal saline)

Alterations in Addenbrooke's Cognitive Exam (ACE III) after intravenous infusion of equivalent doses of dexmedetomidine or placebo (normal saline)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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
Effect of Dexmedetomidine on Brain Homeostasis and Neurocognitive Outcome	NCT04266665	Brain Tumor Metabolic Distu... Inflammatory Re... Oxygen Deficien...	Dexmedetomidine Normal saline	18 Years - 80 Years	Aristotle University Of Thessaloniki

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