Poly-omic Predictors of Symptom Duration and Recovery for Adolescent Concussion

Concussion, Mild Clinical Trial

Official title:

Poly-omic Predictors of Symptom Duration and Recovery for Adolescent Concussion

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04582682
• Other study ID #: STUDY00016155
• Status: Recruiting
• Start date: January 18, 2021
• Est. completion date: January 2026

Study information

• Verified date: February 2024
• Source: Milton S. Hershey Medical Center
• Contact: Steven Hicks, MD, PhD
• Phone: 7175318006
• Email: shicks1[@]pennstatehealth.psu.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to identify changes in salivary micro ribonucleic acid (miRNA) levels that are predictive of symptom duration and character following mild traumatic brain injury (mTBI) in children.

Description:

The objective of this multi-center study is to refine and validate a saliva RNA assessment for adolescent concussion, yielding a non-invasive test that predicts duration and character of symptoms, and helps guide clinical decisions. To accomplish this goal, the study will enroll 750 adolescents with mTBI. Saliva RNA levels and symptoms will be assessed at <48 hours, 7 days, and 30 days post-injury. Aim 1 will assess the ability of saliva RNA dynamics (Δ from <48 hours to day 7) to predict PPCS 30 days after mTBI (defined by persistence of ≥3 symptoms on day 30, compared with pre-injury state on the Post-Concussion Symptom Inventory; PCSI). RNA accuracy will be compared to a validated clinical prediction tool (5p tool). Aim 2 will assess the ability of saliva RNA dynamics (Δ from <48 hours to day 30) to identify recovered participants on day 30. RNA accuracy will be compared to change in composite score on a standardized reaction time test (from <48hrs to day 30). Completion of these aims will yield an objective biologic test that can be used for prognosis at the time of mTBI, and to aid clinical decisions regarding return-to-learn or return-to-play.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 750
• Est. completion date: January 2026
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years to 18 Years

Eligibility

Inclusion Criteria:

• Presence of mTBI: defined by criteria from the Berlin Consensus Statement and WHO. Assessment for mTBI status be performed by a licensed clinician per the 2018 CDC guidelines.

• Age at enrollment: 13-18 years of age (inclusive).

Exclusion Criteria:

• > 48 hours after initial mTBI

• Glasgow Coma Scale score of 13 or less

• Previous moderate-to-severe TBI requiring overnight hospitalization

• Unresolved symptoms from previous concussion, or any concussion within the last 3 months

• Abbreviated Injury Scale (AIS) score > 3 (to reduce confounding from poly-trauma)

• Psychiatric illness requiring previous hospitalization;

• Neurological condition (e.g. epilepsy, hydrocephalus) or abnormality on neuroimaging (if performed)

• Intellectual disability that prevents ability to provide informed assent

• Pregnancy

• Active substance use/dependence

• Previous neurosurgery

• Non-fluency in English

• Upper respiratory infection

• Periodontal infection

• Injury to the oropharynx

• Previously enrolled in the same study

• Inability to complete follow-up assessments

Related Conditions & MeSH terms

• Brain Concussion
• Concussion, Mild

Locations

Country	Name	City	State
United States	Boston Children's Hosptial	Boston	Massachusetts
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Weill Cornell Medicine/ New York Presbyterian Hospital	New York	New York
United States	SUNY Upstate Medical University	Syracuse	New York

Sponsors (2)

Lead Sponsor	Collaborator
Milton S. Hershey Medical Center	National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Presence or absence of persistent post-concussive symptoms (PPCS) 30 days after injury	PPCS will be defined by persistence of at least 3 symptoms on day 30, compared with pre-injury state, which will be determined from pre-injury symptoms reported at enrollment using the Post-Concussion Symptom Inventory (PCSI). PCSI is a self reported survey that focus on symptoms in the cognitive, emotional, sleep, and physical domains. This form is called the "Sport Concussion Assessment Tool- 5th Edition" and symptoms are scored from 0 to 6 with 0 being no symptom and 6 being severe. A high score is indicative of a subject experiencing the worst they have experienced this symptom.	30 days after injury
Primary	Presence or absence of concussion recovery 30 days after injury	Defined as a score of 0 (no difference) on item 22 of the Post-Concussion Symptom Inventory (PCSI); "To what degree do you feel 'differently' than before your injury?" This patient-oriented outcome measure relies on the individual's experience of symptoms to define recovery.PCSI is a self reported survey that focus on symptoms in the cognitive, emotional, sleep, and physical domains. This form is called the "Sport Concussion Assessment Tool- 5th Edition" and symptoms are scored from 0 to 6 with 0 being no symptom and 6 being severe.	30 days after injury
Secondary	Concussion symptom burden and severity	measured as ranked scores by the PCSI at enrollment, PCSI is a self reported survey that focus on symptoms in the cognitive, emotional, sleep, and physical domains. This form is called the "Sport Concussion Assessment Tool- 5th Edition" and symptoms are scored from 0 to 6 with 0 being no symptom and 6 being severe. Symptom burden will be number of symptoms experiencing and severity will be how sever those symptoms are on the 0-6 scale	Within 48 hours of injury, 7 days post-injury, and 30 days post-injury
Secondary	Orientation, immediate memory, concentration, and delayed recall performance	measured as ranked scores by the Standardized Assessment of Concussion (SAC) at enrollment, this test scores cognition using orientation (ex. what is todays date), immediate memory (repeating a list of 10 words), concentration (repeating a list of 3-6 numbers backwards and the months of the year backwards), and delayed recall (recalling the list of 10 words from earlier). Subject receives points for each correct answer with lower scores meaning the concussion has affect the subject more	Within 48 hours of injury
Secondary	Balance performance	measured by the Balance Error Scoring System (BESS) at enrollment, which includes scoring balance on foam and firm surfaces in three different stances for 20 seconds with eyes closed. One point is give per error. An error is credited to the subject when any of the following occur: moving the hands off of the iliac crests, opening the eyes, step stumble or fall, abduction or flexion of the hip beyond 30, lifting the forefoot or heel off of the testing surface, remaining out of the proper testing position for greater than 5 seconds. The maximum total number of errors for any single condition is 10 with 3 conditions (double leg, single leg and tandem stances) each on each foam and firm surfaces the total maximum BESS score is 60 and the lowest score one can achieve is 0. With 0 being the best and 60 being the worst.	Within 48 hours of injury