Predicting Concussion Outcomes With Salivary miRNA

The purpose of this study is to identify changes in salivary ribosomal nucleic acid (RNA) expression that are predictive of symptom duration and character following mild traumatic brain injury (mTBI) in children.

Study Overview

• Status: Recruiting
• Conditions: Concussion, Mild
• Intervention / Treatment: Genetic: salivary RNA collection

Detailed Description

The purpose of this study is to characterize longitudinal salivary RNA expression in 600 children with mTBI and identify RNA patterns that predict length and characterof concussive symptoms, as well as the response to therapy.

Hypothesis: Specific RNAs will be differentially regulated in children with prolonged mTBI symptoms across the acute and sub-acute time periods. The investigators predict that a set of RNAs with differential expression in children with mTBI will be statistically associated with functional measures of mTBI symptoms as well as the duration of concussive symptoms.

Rationale: Preliminary studies show that miRNA is altered in adults with varying degrees of TBI and that salivary RNA is altered by disorders of the CNS. These studies indicate that serum-based miRNA may be used as an accurate biomarker for differentiating adults with and without TBI. Whether similar patterns can seen in the saliva of children following mTBI remains to be seen. Furthermore, the influence of confounding variables such as gender, mechanism of injury, and previous mTBIs on RNA profiles has not been explored. The investigators propose to investigate these questions by examining salivary RNA from 600 children (ages five to twenty-one years) with a clinical diagnosis of mTBI (as well as 100 age-and gender-matched controls, recruited from the Penn State Pediatric Concussion Clinic, Emergency Department, and the affiliated primary care clinics). The investigators plan to prospectively follow 600 children with mTBI for 1-month post-concussion, tracking subjective symptoms with the Child Sports Concussion Assessment Tool (SCAT-5), and objective symptoms of balance and cognition. Saliva will be collected via swab at three time-points (at initial clinical presentation, 1-2 weeks, and 4-weeks after the date of initial mTBI). Expression of salivary RNA taken at initial presentation will be compared against symptom duration (where prolonged post-concussive symptoms are defined as those lasting >4 weeks) and character (as measured numerically by Post-concussion symptom inventory self-report and ClearEdge scoring). The investigators plan to identify a set of salivary RNAs that can easily be used to predict clinical course for pediatric patients following a diagnosis of mTBI.

• Study Type: Observational
• Enrollment (Estimated): 700

Contacts and Locations

• Study Contact: Name: Steven Hicks, MD, PhD; Phone Number: 7175318006; Email: shicks1@hmc.psu.edu

Study Locations

• United States
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Recruiting
      • Penn State Milton S. Hershey Medical Center
      • Contact: Steven Hicks, MD, PhD; Phone Number: 717-531-8006; Email: shicks1@hmc.psu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Children 5-21 years with mild traumatic brain injury

Description

Inclusion Criteria:

• 5-21 years with mild traumatic brain injury that occurred within 7 days of enrollment

Exclusion Criteria:

• Sever traumatic brain injury
• Skull fracture
• Concurrent upper respiratory infection
• Patients whose primary language is not English
• Periodontal infection
• Wards of the state
• Ongoing seizure disorder,
• Drug or alcohol dependency

Study Plan

How is the study designed?

Design Details

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

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Control; No intervention. Collection of medical/demographic info and salivary RNA in children 5-21 years without history of mild traumatic brain injury (mTBI).	Genetic: salivary RNA collection; collection of saliva for microRNA (small noncoding RNA) processing
Concussion; Collection of medical/demographic info and salivary RNA in children 5-21 years with history of mild traumatic brain injury (mTBI). Collection of PCSI concussion assessment interview tool and balance/cognition testing at time of injury, 1-2wks post injury, and 4wks post injury.	Genetic: salivary RNA collection; collection of saliva for microRNA (small noncoding RNA) processing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence or absence of concussion symptoms	subjective (score >7 on PCSI) or objective (score outside 85 percentile on accelerometer balance testing or cognitive testing)	4-weeks post injury

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Salivary RNA profile	measured with RNAseq	Within 7d of initial injury, 1-2 weeks post-injury, and 4-weeks post-injury

Collaborators and Investigators

• Sponsor: Milton S. Hershey Medical Center
• Investigators: Principal Investigator: Steven Hicks, MD, PhD, Milton S. Hershey Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: September 12, 2016
• First Submitted That Met QC Criteria: September 14, 2016
• First Posted (Estimated): September 15, 2016

Study Record Updates

• Last Update Posted (Actual): September 29, 2023
• Last Update Submitted That Met QC Criteria: September 27, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds, Nonpenetrating; Brain Injuries; Brain Injuries, Traumatic; Brain Concussion
• Other Study ID Numbers: STUDY00003729