Salivary Biomarkers for Concussion Recovery
Condition: Concussion, Brain
MeSH terms: Brain Concussion
Study type: Interventional

Summary: 
      The overarching purpose of this proposed research is to determine whether BDNF and/or
      specific miRNAs can serve as biomarkers for recovery from a concussion during prescribed
      exercise. The investigators hypothesize salivary BDNF and specific miRNA signatures will
      change in a statistically significant manner as participants proceed from injury to recovery
      and participants who show recovery in ANS regulation will show significant differences in
      salivary BDNF and specific miRNA expression. This study also aims to determine if BDNF and/or
      specific miRNA can serve as biomarkers of the return of ANS function in concussed patients.
      The basic premise here is that the volume of exercise will significantly affect the rate of
      change in the expression of salivary BDNF and miRNA from injury to recovery.
    

Detailed description: 
      -  This is a four-arm randomized control trial that investigates the changes in expression
           of BDNF/ miRNA after prescribed exercise intervention in concussed adolescents.
           Potential participants will be selected from incoming patients to the University
           Concussion Management Clinic. For a patient to become a potential participant in the
           "concussed participant" group, a sports medicine physician must first confirm the
           diagnosis of an acute concussion within 10 days of injury. Healthy controls will be
           recruited at local high schools (pediatric) and from the UB Clinical Trial registry
           (pediatric and adult). Concussion diagnosis is based on history, a concussion symptom
           questionnaire, and a concussion-specific physical examination. If the participant's
           medical history and demographic information meet eligibility criteria, they will be
           asked if they would like to participate. All potential participants will be informed of
           all study procedures verbally. If participants are willing and eligible to participate,
           they will be asked to consent/ assent to the study procedure.

        -  Participants will be asked to fill out the documentation regarding their demographics,
           concussion symptoms/history (Concussion Symptom Evaluation, Post-Concussion Symptom
           Inventory), and motivation to exercise (Modified Perceived Competence Scale, Modified
           Treatment Self-Regulation Questionnaire). Additionally, to determine if participants
           have any contraindications to exercise, the Physical Activity Readiness Questionnaire
           (PAR-Q) will be completed by all participants.

        -  Participants will undergo the Buffalo Concussion Physical Exam (BCPE), a short
           examination to used determine if a patient is concussed. This examination includes vital
           signs, a head and neck examination, cranial nerve testing, oculomotor testing, and a
           balance test.

        -  A trained examiner will complete an Oral Hygiene Index-Simplified (OHI-S) and will
           collect saliva. The Oral Hygiene Index is a short evaluation of the calculus and debris
           on selected teeth to assess the oral hygiene of a participant. Saliva will be collected
           using a Genotek Swab (miRNA) and a Salimetrics Cryovial (BDNF). Saliva will be collected
           with a swab (Genotek) and passive drool (Salimetrics) techniques.

        -  After saliva is obtained, the participant will be asked to complete the Buffalo
           Concussion Treadmill Test (BCTT). The BCTT is a graded exercise test that is used to
           determine concussion-related exercise intolerance. Although it is standard for patients
           from the Concussion Clinic to require a BCTT assessment as a part of their standard
           visit, participants will be made aware that their BCTT data will be used for this study.
           During the BCTT participants will be asked to wear an HR monitor (Polar H10) for the
           collection of HR and Heart Rate Variability (HRV) data.

        -  After completion of the BCTT, the examiner will use the results of the exercise test to
           create an individualized exercise prescription. The prescription will be randomized for
           high and low volumes and even split between male and female participants in healthy and
           concussed groups.

        -  Recovery date for concussed participants will be provided by the study clinician after
           the end of the intervention if concussed participants do not recover during the study
           time frame.
    

Intervention name(s): High Volume Aerobic Exercise; Low Volume Aerobic Exercise
Intervention type(s): Behavioral; Behavioral
Intervention description(s): Aerobic exercise is completed for 30 minutes, 5 days a week. Exercise intensity is adjusted weekly to 90% of the heart rate threshold. Exercise interventions for all participants are adjusted to the 90% Heart rate threshold (HRt) collected on the BCTT.; Aerobic exercise is completed for 20 minutes, 3 days a week. Exercise intensity is adjusted weekly to 90% of the heart rate threshold. Exercise interventions for all participants are adjusted to the 90% Heart rate threshold (HRt) collected on the BCTT.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants will be randomly assigned into 4-arms: (1) Concussed participants: high volume exercise, (2) Concussed participants: low volume exercise, (3) Healthy controls: high volume exercise, (4) Healthy controls: low volume exercise. Each group will consist of 50% males and 50% females. Exercise interventions for all participants are adjusted to the 90% Heart rate threshold (HRt) collected on the BCTT. The high-volume group will exercise aerobically at 90% of their HRt for 5 days a week for 30 minutes. The low volume group will exercise aerobically at 90% of their HRt for 3 days a week for 30 minutes. The intervention will last 2 weeks. Participants will return to the clinic and repeat testing on Days 7 and 14. Recovery is defined as (1) resolution of concussion symptoms (2) physical examination within normal limits; (3) ability to exercise to at least 80% of age-appropriate maximum HR without exacerbation of concussion-like symptoms on the BCTT.
Masking: Single (Care Provider)
Primary purpose: Treatment
Keywords: adolescent; exercise; aerobic; biomarker; recovery