Salivary Biomarkers in Pediatric Traumatic Brain Injury

Studying the Significance of Salivary Biomarkers in Pediatric Traumatic Brain Injury

By studying individual biomarkers in body fluids such as saliva, there is a potential for detecting injury to the brain resulting from an acute traumatic even that may not be detectable by conventional neuroimaging like CT scans.

Study Overview

• Status: Completed
• Conditions: Traumatic Brain Injury

Detailed Description

Although identification of biomarkers following TBI is a rather novel area of research, few studies that have been done in patients with severe TBI and biomarkers from serum and cerebrospinal fluid have shown to have prognostic significance. However there are no prior studies looking at biomarkers in salivary specimens. In this study we will include patients with moderate and severe TBI who require inpatient admission, and will study 3 specific salivary biomarkers. This is a unique project, since salivary specimen collection is easy and non-invasive and can be collected at any site even on a sports field by using a simple absorbable swab resembling a cigarette stub, unlike blood or CSF that can be highly invasive. Salivary specimens can also be frozen and stored for long periods of time prior to testing. If our study detects abnormalities in levels of these biomarkers when compared to healthy controls, and children with extra-cerebral injuries, in future studies we can look at children and adolescents with minor head traumas and concussions who are discharged from the emergency department after evaluation, and study their long-term outcomes and correlation with salivary biomarkers.

Specific aims:

To study levels of three specific biomarkers in salivary specimens (GFAP, S100B and NSE) in children with moderate TBI (GCS: 9-12) and severe TBI (GCS: <8) admitted to a pediatric trauma referral center. These biomarkers have been shown to have prognostic significance in prior studies using serum and CSF.

• Study Type: Observational
• Enrollment (Actual): 77

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85008
      • Maricopa Integrated Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

1) Children aged 0 to 20 who present to the pediatric ED or trauma bay with an isolated acute head injury (moderate or severe) and are admitted for inpatient management; 2) pediatric patients who present to the ED with non-trauma complaints; and 3) pediatric patients who present to the ED with non-head trauma such as musculoskeletal injuries.

Description

Inclusion Criteria:

• Children aged 0 to 20 who present to the pediatric ED or trauma bay with an isolated acute head injury (moderate or severe) and are admitted for inpatient management;
• Pediatric patients who present to the ED with non-trauma complaints; and
• Pediatric patients who present to the ED with non-head trauma such as musculoskeletal injuries.

Exclusion Criteria:

• Patients with multisystem trauma;
• Patients with minor head trauma (GCS 13-15) discharged from the pediatric ED
• Patients with other pre-existing neurological conditions (such as cerebral palsy, chronic seizure disorder, VP shunts);
• Patients with a history suggestive of head trauma from chronic abuse;
• Incarcerated patients or patients from juvenile detention facilities;
• Refusal of parent/patient to participate for any specific reason.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Control Group 1; Children with non-trauma complaints
Control Group 2; Children with non TBI and musculoskeletal trauma
Cases; Children admitted to hospital with moderate/severe isolatedTBI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of 3 specific salivary biomarkers (GFAP, S100B, and NSE)	Within 24 hours of an acute isolated TBI	Within 24 hours of injury

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glasgow Coma Scale measurement of injury severity	Glasgow Coma Scale is a score between 3 and 15, 3 being the worst, and 15 the best. It is composed of three parameters: Best Eye Response, Best Verbal Response, and Best Motor Response. A Coma Score of 13 or higher correlates with a mild brain injury, 9 to 12 is a moderate injury and 8 or less a severe brain injury.	Day 1
Brain CT Scan abnormalities suggesting significant brain injury	Dichotomous measure: presence or absence of such abnormalities	Within 24 hours of injury
Need for mechanical ventilation	Mechanical ventilators are used for patients who cannot breathe by themselves. Dichotomous measure: whether or not mechanical ventilation is needed.	During hospitalization (up to 50 days)
Need for neurosurgical intervention including ICP monitor	Dichotomous measure: whether or not neurosurgical intervention is needed	During hospitalization (up to 50 days)
Patient's Length of Stay or hospitalization	Number of days spent in hospital	Duration of hospitalization (up to 50 days)
Final disposition	Polytomous measure: Discharge to home, discharge to rehab, or death	At end of hospitalization (up to 50 days)

Collaborators and Investigators

• Sponsor: Valleywise Health
• Investigators: Study Director: Claudia Yeung, MD, ValleyWise Health; Study Director: Kevin Foster, MD, ValleyWise Health

Publications and helpful links

General Publications

• Zetterberg H, Smith DH, Blennow K. Biomarkers of mild traumatic brain injury in cerebrospinal fluid and blood. Nat Rev Neurol. 2013 Apr;9(4):201-10. doi: 10.1038/nrneurol.2013.9. Epub 2013 Feb 12.
• Olsson B, Zetterberg H, Hampel H, Blennow K. Biomarker-based dissection of neurodegenerative diseases. Prog Neurobiol. 2011 Dec;95(4):520-34. doi: 10.1016/j.pneurobio.2011.04.006. Epub 2011 Apr 16.
• Faul M, Xu L, Wald MM, Coronado V. Traumatic brain injury in the United States: emergency department visits, hospitalizations, and deaths, 2002--2006. Atlanta, GA: CDC, National Center for Injury Prevention and Control; 2010.

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2014
• Primary Completion (Actual): March 17, 2017
• Study Completion (Actual): March 30, 2017

Study Registration Dates

• First Submitted: October 16, 2014
• First Submitted That Met QC Criteria: November 17, 2015
• First Posted (Estimate): November 20, 2015

Study Record Updates

• Last Update Posted (Actual): September 14, 2017
• Last Update Submitted That Met QC Criteria: September 12, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Children; Head injury; Salivary biomarker; Trauma Brain Injury
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic
• Other Study ID Numbers: 2014-055