Monitoring & Mitigation of Neurologic Injuries to Optimize Resilience After Repetitive Head Impacts (MONITOR-RHI)

The purpose of this Phase 2, double-arm study is to identify repetitive, non-concussive head impacts that impair neurologic functioning, and to test treatments that can mitigate these effects and return functioning to normal as quickly as possible.

Study Overview

• Status: Enrolling by invitation
• Conditions: Head Injuries
• Intervention / Treatment: Other: Aerobic exercise

Detailed Description

Up to 350 total collegiate athletes and athlete-cadets will be enrolled. Approximately 290 participants participating in varsity contact sports (e.g. soccer, football, etc.) at colleges/universities or military colleges, and up to 60 non-contact athletes/cadets participating in non-contact varsity sports (e.g. swimming, tennis, etc.) will be recruited as controls for the Observational arm; approximately half the participants will be female.

• Study Type: Interventional
• Enrollment (Estimated): 350
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • Amherst, New York, United States, 14221
      • University at Buffalo
    • Rochester, New York, United States, 14620
      • University of Rochester
  • South Carolina
    • Charleston, South Carolina, United States, 29409
      • The Citadel, The Military College of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age ≥ 18 years
• Collegiate athlete or athlete-cadet anticipated to be an active member of a varsity sport team.

Exclusion Criteria:

• Any head, neck, or face injury in the 3 months prior to enrollment that precludes participation in contact sports or wearing a mouth guard sensor
• History of neurological or psychiatric disorders or neurological disorders that impact electrical activity in the brain (such as seizure disorders), or diagnosed learning disability, that in the opinion of the investigator, would interfere with participation in the study.
• Participants currently undergoing active treatment for migraine, depression and/or anxiety or ADHD will not be excluded as these are high prevalence conditions in the adolescent and collegiate population (8-30%). However, exploratory stratified analyses will be conducted where possible.
• Participants with eye conditions or diseases that could impact the blood vessels in the eye.
• Determination that the participant is unsuitable for study entry or potentially unable to complete all aspects of the study based on the judgement of the Site Investigator or Study PI.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Observational (Ad-Lib Exercise) Arm; All participants will undergo neurologic outcome testing with optical coherence tomography/angiography (OCT/A) at pre- and post-season and 2 weeks after the end of the season. For two weeks at the end of the sport season, participants will be instructed to refrain from sports involving head contact but to otherwise exercise ad-lib.
Experimental: Intervention (Exercise or Stretching) Arm; Athletes and athlete cadets will be administered OCT/A and a novel neurologic test battery at pre- and post-season, and 2 weeks after the end of the season. After the end-of-season assessments, participants will be randomized to 2 weeks of either 30 minutes of daily aerobic exercise or to 30-minutes of prescribed stretching.	Other: Aerobic exercise; After the end-of-season assessments, participants in the Intervention (Exercise or Stretching) arm will be randomized to 2 weeks of daily aerobic exercise for 30 minutes or to 30-minutes of prescribed stretching.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Optical Coherence Tomography (OCT) of Cerebrospinal Fluid Thickness in the Macula (Part of the Retina)	A primary OCT variables examined will be macula cerebrospinal fluid (CSF) thickness (an indicator of the gain or loss of neurons or glia in the inner nuclear, ganglion cell and nerve fiber layer).	Pre-season and post-season, 2 weeks
Change in Blood Serum Concentrations of Glial Fibrillary Acidic Protein (GFAP)	Glial Fibrillary Acidic Protein (GFAP) concentration will determine if there is a 11.9 pg/mL or greater change in GFAP in each participant over the course of the study.	Baseline 4 to 7 months
Change in Blood Serum Concentration of Neurofilament light chain (NfL) in a blood sample	The neurologic test battery consists of blood draws for serum brain proteins: Neurofilament light chain (NfL) concentrations will be observed for changes over the course of the study.	Baseline 4 to 7 months
Change in p-231Tau serum concentration in a blood sample	The neurologic test battery consists of blood draws for serum brain proteins: p231Tau will be observed for changes over the course of the study.	Baseline 4 to 7 months
Change in Concussion Index as measured with Quantitative Electroencephalogram (qEEG)	The Quantitative Electroencephalogram (qEEG) Concussion Index (CI) includes measures of power (absolute and relative), mean frequency, connectivity (asymmetry, coherence, phase lag, phase synchrony), complexity (fractal dimension and scale-free activity), and information theory (entropy), across and within frequency bands.	Baseline 4 to 7 months
Change in near-point convergence (NPC)	Near point of convergence (NPC) is a measurement of how close an object can be brought to the eyes while the eyes are focused on it.	Baseline 4 to 7 months
Change in Choice reaction time (CRT)	Choice reaction time (CRT) refers to the time it takes for a person to react to a stimulus by selecting a specific response from multiple options.	Baseline 4 to 7 months
Change in blink reflex test	A blink reflex test, also known as a corneal reflex test, is a non-invasive procedure that measures the electrical activity of the facial nerves when stimulated.	Baseline 4 to 7 months
Optical Coherence Tomography (OCT) to detect signs of neurodegenertaion in the Retina	OCT will be used to measure the cup-to-disc ratio of the optic disc, and indicator of neurodegeneration.	Pre-season and post-season, 2 weeks
Optical Coherence Tomography/Angiography (OCT/A) to assess the vascular structure in the retina	Retinal vascular structure will be acquired using the OCT angiography (OCT/A). The primary OCT/A variable examined will be foveal avascular zone (FAZ) area reflecting the size of the central portion of the macula which contains no blood vessels, and which increases in size with loss of capillaries in the surrounding region).	Pre-season and post-season, 2 weeks

Collaborators and Investigators

• Sponsor: University of Rochester

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2025
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: January 25, 2025
• First Submitted That Met QC Criteria: January 30, 2025
• First Posted (Actual): February 5, 2025

Study Record Updates

• Last Update Posted (Estimated): September 11, 2025
• Last Update Submitted That Met QC Criteria: September 9, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Repetitive Head Impacts
• Additional Relevant MeSH Terms: Nervous System Diseases; Wounds and Injuries; Trauma, Nervous System; Craniocerebral Trauma; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Exercise
• Other Study ID Numbers: STUDY00010101; US Department of Defense (Other Identifier: US Army Medical Research Acquisition Activity)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No