Modulating Exercise Dosage to Improve Concussion Recovery

NCT05434130 | Recruiting Phase 2 DMC

• 2 other identifiers: 21-4932R01HD108133
• Study Type: interventional
• Target: 216
• Locations: 1 country
• Sites: 3

Brief Summary

Aerobic exercise has emerged as an effective treatment to reduce sport-related concussion symptom severity, yet existing work lacks rigor regarding the precise exercise volume and intensity required to elicit therapeutic effects, how exercise can alter concussion-related pathophysiology, and whether exercise can prevent the development of secondary sequelae. Our objective is to examine if a high dose exercise program (higher volume than currently prescribed at an individualized, safe intensity level) initiated within 14 days of concussion results in faster symptom resolution, altered physiological function, or reduced secondary sequalae. Findings from this research will lead to more rigorous and precise rehabilitation guidelines and improved understanding about how exercise affects neurophysiological function among adolescents with concussion.

Conditions

Concussion, Brain; Treatment; Aerobic Exercise; Inflammation; Depression, Anxiety

Keywords

intervention; mild traumatic brain injury

Outcome Measures

Primary Outcomes (3)

• Time from injury to symptom resolution

  The PCSS is a standard form that records the presence and severity of 22 concussion symptoms at the time of testing. Participants rate their concussion symptoms from 0-6 where 0 equates to "no symptoms," and 6 to "severe symptoms."

  From time of injury until defined symptom resolution observed, about 30 days

• Serum biomarker concentration: GFAP change

  Concentrations of GFAP will be simultaneously assayed along with other biomarkers using multi-plex digital array technology, which allows for single molecule immunoarrays while minimizing the amount of sample required

  Baseline, Visit 2 (scheduled after symptoms resolve, about 35 days post-baseline)

• Anxiety and depression severity change

  Participants will report anxiety using the Hospital Anxiety and Depression Scale (HADS).The HADS addresses questions related to depression and anxiety symptoms. Responses range from 0 to 3, where 3=experiencing symptoms a great deal of the time, on 14 questions. Seven items are specific to depression symptoms, and 7 to anxiety symptoms. For each sub-scale (HADS-anxiety and HADS-depression) scores range from 0 (no symptoms) to 21 (maximum symptom severity).

  Baseline, Visit 2 (scheduled after symptoms resolve, about 35 days post-baseline)

Secondary Outcomes (10)

• Serum biomarker concentration: IL-6 change

  Baseline, Visit 2 (scheduled after symptoms resolve, about 35 days post-baseline)

• Serum biomarker concentration: TNF-alpha change

  Baseline, Visit 2 (scheduled after symptoms resolve, about 35 days post-baseline)

• Serum biomarker concentration: IL1-RA change

  Baseline, Visit 2 (scheduled after symptoms resolve, about 35 days post-baseline)

• Serum biomarker concentration: VEGF change

  Baseline, Visit 2 (scheduled after symptoms resolve, about 35 days post-baseline)

• Serum biomarker concentration: MMP-9 change

  Baseline, Visit 2 (scheduled after symptoms resolve, about 35 days post-baseline)

Study Arms (2)

High Dose Exercise

EXPERIMENTAL

The investigators will provide exercise dose recommendations for initial visit until symptom resolution, and revise upon symptom resolution (to use for the subsequent 8 weeks). These include intensity (target HR) and volume (frequency/duration). Intensity is calculated as 90% of the HR at the end of the exercise test. The volume recommendation is 150 mins/week (\~30 min/day; 5 days/week). The mode of exercise is another consideration. This will be left to participant preference, so that the investigators do not exclude potential participants due to lack of access to specific exercise equipment.

Behavioral: High Dose Exercise

Standard-of-care

NO INTERVENTION

Participants are instructed to perform activity in line with physician recommendations. This consists of a general recommendation (no specific HR/volume) or symptom limited physical activity.

Interventions

High Dose Exercise BEHAVIORAL

The investigators will initially test and randomize adolescents ages 13-18 years old ≤14 days post-concussion to high dose aerobic exercise (\>150 min/week, individualized intensity level) or standard-of-care (symptom limited, self-guided physical activity), and re-test upon symptom resolution and 8-weeks post symptom resolution

High Dose Exercise

Eligibility Criteria

• Age: 13 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• years of age
• Post-Concussion Symptom Scale (PCSS) score \>10 to ensure participants are not recovered by enrollment
• Concussion diagnosis by a sports medicine physician

You may not qualify if:

• Pre-existing neurological disorders
• Exercise contraindications
• Concussion \<6 months before enrollment (excluding the current injury)

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Boston Children's Hospital: collaborator
• Spaulding Rehabilitation Hospital: collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (3)

University of Colorado Denver

Aurora, Colorado, 80045, United States

RECRUITING

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Spaulding Rehabilitation Hospital

Cambridge, Massachusetts, 02138, United States

RECRUITING

MeSH Terms

Conditions

Brain Concussion; Inflammation; Depression; Anxiety Disorders

Interventions

Exercise

Condition Hierarchy (Ancestors)

Brain Injuries, Traumatic; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds and Injuries; Wounds, Nonpenetrating; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavioral Symptoms; Behavior; Mental Disorders

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• David R Howell, PhD

  University of Colorado Denver | Anschutz

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David R Howell, PhD

CONTACT

7207771502; ConcussionResearch@cuanschutz.edu

Kelsie Richardson, MS

CONTACT

7207771502; ConcussionResearch@cuanschutz.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study PI, Co-Is, and the biostatistician will not know group assignments until after the primary analyses are complete.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study will use a block stratified RCT design. Our stratum factors are the biological variable of sex and recruitment location

Study Record Dates

• First Submitted: May 26, 2022
• First Posted: June 27, 2022
• Study Start: August 5, 2022
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)