Salivary Biomarkers for Concussion Recovery

Epigenetic and Cytokine Biomarkers During Recovery From Sports-Related Concussion

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.

Study Overview

• Status: Completed
• Conditions: Concussion, Brain
• Intervention / Treatment: Behavioral: High Volume Aerobic Exercise; Behavioral: Low Volume Aerobic Exercise

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14214
      • UB MD Orthopeadics & Sports Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Adolescent and adult athletes (age 13-18) diagnosed with SRC within 10 days of injury.

Exclusion Criteria:

• Evidence of focal neurological deficit;
• Inability to exercise because of orthopedic or cervical spine injury;
• Increased cardiac risk according to American College of Sports Medicine criteria;
• History of moderate or severe TBI, defined as brain injury with a Glasgow Coma Scale score of 12 or less;
• Current medication treatment for ADHD, learning disorders, depression, anxiety, or other medications that can affect HR;
• Symptom severity score of less than 5 on the initial visit Post Concussion Symptom Scale questionnaire. (7) currently pregnant (8) have any contraindications to exercise (Physical Activity Readiness-Questionnaire)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Concussed Participants Group 1; High Volume Group	Behavioral: High Volume Aerobic Exercise; 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.
Experimental: Concussed Participants Group 2; Low Volume Group	Behavioral: Low Volume Aerobic Exercise; 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.
Active Comparator: Healthy controls Group 1; High Volume Group	Behavioral: High Volume Aerobic Exercise; 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.
Active Comparator: Healthy Controls Group 2; Low Volume Group	Behavioral: Low Volume Aerobic Exercise; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Persistent Post Concussion Symptoms (PPCS) (Yes/No)	PPCS is defined as more recovery that occurs 28 days or more from the day of concussive injury (yes) or before 28 days (no). Recovery is defined as asymptomatic, exercise tolerant and confirmation by independent medical examination.	28 days

Collaborators and Investigators

• Sponsor: State University of New York at Buffalo
• Collaborators: National Center for Advancing Translational Sciences (NCATS)
• Investigators: Study Director: John Leddy, MD, University at Buffalo; Study Chair: Barry Willer, PhD, University at Buffalo; Principal Investigator: Praveen Arany, DDS, PhD, University at Buffalo; Study Director: Mohammad Nadir, MD, PhD, University at Buffalo

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2022
• Primary Completion (Actual): January 13, 2023
• Study Completion (Actual): January 13, 2023

Study Registration Dates

• First Submitted: March 1, 2022
• First Submitted That Met QC Criteria: May 13, 2022
• First Posted (Actual): May 18, 2022

Study Record Updates

• Last Update Posted (Estimated): January 3, 2024
• Last Update Submitted That Met QC Criteria: December 13, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: exercise; adolescent; biomarker; recovery; aerobic
• 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: STUDY00005734; UL1TR001412 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan to share IPD currently

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No