The Effect of Exercise on Neurorecovery Following Mild Traumatic Brain Injury

Brain Concussion Clinical Trial

Official title:

The Effect of Exercise on Neurorecovery Following Mild Traumatic Brain Injury

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02276079
• Other study ID #: IRB201400882
• Status: Completed
• Phase: N/A
• Start date: February 17, 2015
• Est. completion date: December 22, 2016

Study information

• Verified date: November 2018
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study is a "proof-of-principle" project to examine the safety and feasibility of implementing a 1-week aerobic exercise program in the post-acute phase after mild traumatic brain injury (mTBI). The study will define the extent to which the exercise program improves recovery from mTBI in terms of relevant functional outcomes (cognition, mood, and physical status) and biomarkers (peripheral brain-derived neurotrophic factor [BDNF] concentration).

Description:

This is a "proof-of-principle" project for human subjects to examine the safety and feasibility of implementing a 1-week aerobic exercise program in the post-acute phase after mild traumatic brain injury (mTBI). This study will define the extent to which the exercise program improves recovery from mTBI in terms of relevant functional outcomes (cognition, mood, and physical status) and biomarkers (peripheral brain-derived neurotrophic factor [BDNF] concentration). This project will also lay the foundation for understanding the relationship between exercise and BDNF in the area of mTBI neurorecovery, thereby allowing future studies to develop best-practice methods for implementing exercise interventions as a treatment option for brain injuries.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: December 22, 2016
• Est. primary completion date: December 22, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

Mild traumatic brain injury (mTBI) group:

Inclusion Criteria:

• Meet criteria for mTBI as set forth by the American Congress of Rehabilitation Medicine

• mTBI was sustained 14-25 days before beginning the exercise intervention

Exclusion Criteria:

• comorbid orthopaedic injury that inhibits movement

• history of serious psychiatric disturbance with hospitalization,

• prior history of neurologic disease,

• current or past history of substance abuse disorder,

• diabetes

• previous history of moderate or severe head injury,

• neurological disorder unrelated to TBI (e.g., seizure disorder)

• physician recommendations against exercise

• non-English speakers

Non-injured Group:

Inclusion Criteria:

• Gainesville, Florida community member

Exclusion Criteria:

• History of mTBI or other brain injury in the past year

• comorbid orthopaedic injury that inhibits movement

• history of serious psychiatric disturbance with hospitalization,

• prior history of neurologic disease,

• current or past history of substance abuse disorder,

• diabetes

• previous history of moderate or severe head injury,

• neurological disorder unrelated to TBI (e.g., seizure disorder)

• physician recommendations against exercise

• non-English speakers

Related Conditions & MeSH terms

• Brain Concussion
• Brain Injuries
• Brain Injuries, Traumatic

Intervention

Behavioral:
• Aerobic Exercise
Aerobic exercise will consist of riding a stationary bicycle at moderate intensity for 2 consecutive, 20-minute periods with a 5-minute break in between. Moderate intensity is defined as maintaining 65-75% of estimated maximum heart rate based on the calculation (HRmax = 208 - 0.7 × age).
• Non-Aerobic Exercise
Non-Aerobic exercise will consist of very low-intensity movements including static stretching and toning exercises.Participants will complete 2 consecutive, 20-minute periods with a 5-minute break in between, mirroring the aerobic exercise condition. Heart rate will be monitored by research staff to ensure that it remains below 50% of estimated maximum heart rate.

Locations

Country	Name	City	State
United States	University of Florida Health Science Center	Gainesville	Florida

Sponsors (4)

Lead Sponsor	Collaborator
University of Florida	American Psychological Association (APA), American Psychological Foundation, Clinical & Translational Science Institute

Country where clinical trial is conducted

United States, 

References & Publications (12)

Barkhoudarian G, Hovda DA, Giza CC. The molecular pathophysiology of concussive brain injury. Clin Sports Med. 2011 Jan;30(1):33-48, vii-iii. doi: 10.1016/j.csm.2010.09.001. Review. — View Citation

Bigler ED. Neuropsychology and clinical neuroscience of persistent post-concussive syndrome. J Int Neuropsychol Soc. 2008 Jan;14(1):1-22. Review. — View Citation

Cassidy JD, Carroll LJ, Peloso PM, Borg J, von Holst H, Holm L, Kraus J, Coronado VG; WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury. Incidence, risk factors and prevention of mild traumatic brain injury: results of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury. J Rehabil Med. 2004 Feb;(43 Suppl):28-60. Review. — View Citation

Coelho FG, Gobbi S, Andreatto CA, Corazza DI, Pedroso RV, Santos-Galduróz RF. Physical exercise modulates peripheral levels of brain-derived neurotrophic factor (BDNF): a systematic review of experimental studies in the elderly. Arch Gerontol Geriatr. 2013 Jan-Feb;56(1):10-5. doi: 10.1016/j.archger.2012.06.003. Epub 2012 Jun 29. Review. — View Citation

Dunn AL, Trivedi MH, Kampert JB, Clark CG, Chambliss HO. The DOSE study: a clinical trial to examine efficacy and dose response of exercise as treatment for depression. Control Clin Trials. 2002 Oct;23(5):584-603. — View Citation

Efird J. Blocked randomization with randomly selected block sizes. Int J Environ Res Public Health. 2011 Jan;8(1):15-20. doi: 10.3390/ijerph8010015. Epub 2010 Dec 23. — View Citation

Griesbach GS, Gómez-Pinilla F, Hovda DA. Time window for voluntary exercise-induced increases in hippocampal neuroplasticity molecules after traumatic brain injury is severity dependent. J Neurotrauma. 2007 Jul;24(7):1161-71. — View Citation

Griesbach GS, Hovda DA, Gomez-Pinilla F. Exercise-induced improvement in cognitive performance after traumatic brain injury in rats is dependent on BDNF activation. Brain Res. 2009 Sep 8;1288:105-15. doi: 10.1016/j.brainres.2009.06.045. Epub 2009 Jun 23. — View Citation

Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009 Apr;42(2):377-81. doi: 10.1016/j.jbi.2008.08.010. Epub 2008 Sep 30. — View Citation

Prins ML, Alexander D, Giza CC, Hovda DA. Repeated mild traumatic brain injury: mechanisms of cerebral vulnerability. J Neurotrauma. 2013 Jan 1;30(1):30-8. doi: 10.1089/neu.2012.2399. — View Citation

Riemann BL, Guskiewicz KM. Effects of mild head injury on postural stability as measured through clinical balance testing. J Athl Train. 2000 Jan;35(1):19-25. — View Citation

Tanaka H, Monahan KD, Seals DR. Age-predicted maximal heart rate revisited. J Am Coll Cardiol. 2001 Jan;37(1):153-6. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in aerobic fitness	Measured by the 3-Minute Step Test, which provides an estimate of aerobic fitness. Participants step up and down continuously on a 12-inch step for 3 minutes and the time it takes for their heart rate to return to baseline is recorded.	Baseline and up to day 8
Other	Change in body weight	Body weight measured in kilograms.	Baseline and up to day 8
Other	Minutes of physical activity outside of exercise program	Average number of minutes the participant spent engaging in physical activity outside of the exercise sessions during the one-week exercise program. This will be measured by a digital fitness monitor that will be worn 24 hours per day during the 7 day exercise program.	Day 7 of exercise program
Primary	Change in Symptom Score on the Sport Concussion Assessment Tool (SCAT3)	Obtained from the 22-item symptom evaluation included in the Sport Concussion Assessment Tool (SCAT3). The participant's present experience of each symptom is rated on a likert scale from 0 (none) to 6 (severe). The symptom score represents how many symptoms the participant endorses experiencing at a level greater than 0 (maximum 22 points).	Baseline and up to day 8
Primary	Change in Symptom Severity on the Sport Concussion Assessment Tool (SCAT3)	Symptom evaluation included in the Sport Concussion Assessment Tool (SCAT3). The participant's present experience of each symptom is rated on a likert scale from 0 (none) to 6 (severe). The symptom severity represents the total summed severity ratings for all symptoms (maximum 132 points).	Baseline and up to day 8
Primary	Change in sleep quality	Obtained from the Medical Outcomes Sleep Scale (MOS). This measure has 12 items and asks the participant to rate different aspects of their sleep experiences and sleep quality. The first two questions inquire about sleep times and the remaining questions utilize a likert scale ranging from 1 (all of the time) to 6 (none of the time). Some items are reverse scored and the scale yields several subscale measures, so scoring rules depend on the specific subscale.	Baseline and up to day 8
Primary	Change in postural stability	The Balance Error Scoring System (BESS) will be used to measure postural stability, which is sensitive to deficits in balance following mild head injury. A modified version of (SCAT3) will be used. It includes three different stances, double leg, single leg, and tandem stance. A point is added for committing an error during the test interval and if the participant is unable to maintain his or her balance for more than 5 seconds, the trial is discontinued and maximum points are awarded. The total score ranges from 0 (better postural stability) to 30 (worse postural stability).	Baseline and up to day 8
Primary	Change in verbal learning and memory	Measured by the California Verbal Learning Test, 2nd Edition (CVLT-II). This test measures word recall and assesses the following skills: immediate recall, short delay free recall, short delay cued recall, long delay free recall, long delay cued recall, and long delay recognition.	Baseline and up to day 8
Primary	Change in auditory-linguistic memory	Measured by the Wechsler Memory Scale, 3rd Edition (WMS-III), Logical Memory subtests. Two stories are read to participants and then they are asked to freely recall items after a short and a long delay. A recognition trial is administered following the long delay.	Baseline and up to day 8
Primary	Change in word-fluency	Measured by the Controlled Oral Word Association (COWA). Participants are asked to say as many words beginning with a specified letter as they can in a one minute time period. Three trials with different letters are administered.	Baseline and up to day 8
Primary	Change in semantic fluency	Measured by the Verbal Fluency Test - Categories. Participants are asked to say as many items belonging to a specified semantic category as they can in a one minute time period.	Baseline and up to day 8
Primary	Change in psychomotor/executive functioning	Measured by the Delis-Kaplan Executive Functioning System (D-KEFS), Trail Making Test. The test consists of five different conditions where participants are asked to draw trails according to specified rules.	Baseline and up to day 8
Primary	Change in problem solving and abstract reasoning	Measured by the Wisconsin Card Sorting Test (WCST). Initially, a number of stimulus cards are presented to the participant. The participant is told to match the cards, but not how to match; however, he or she is told whether a particular match is right or wrong. A total of 128 cards are played.	Baseline and up to day 8
Primary	Change in attention	Measured by the Wechsler Adult Intelligence Scale, 3rd Edition (WAIS-III), Digit Span subtest. Participants are asked to repeat digit strings that are verbally administered exactly as they hear them (digits forward) or to repeat them backwards (digits backward).	Baseline and up to day 8
Primary	Change in processing speed	Measured by the Wechsler Adult Intelligence Scale, 3rd Edition (WAIS-III), Digit Symbol-Coding subtest. Participants are given three minutes to draw symbols as quickly and as accurately as possible according to a key code.	Baseline and up to day 8
Primary	Change in visual memory	Measured by the Wechsler Memory Scale, 3rd Edition (WMS-III), Visual Reproduction subtest. Participants are asked to draw abstract figures from memory at different time intervals. The subtest assesses the following visual memory skills: immediate free recall, long delayed free recall and a long delayed recognition.	Baseline and up to day 8
Primary	Change in sustained and selective attention	Measured by the Ruff 2 & 7 Selective Attention Test. The test consists of a series of 20 trials of a visual search and cancellation task. The participant detects and marks through all occurrences of the two target digits: "2" and "7." In the 10 Automatic Detection trials, the target digits are embedded among alphabetical letters that serve as distractors. In the 10 Controlled Search trials, the target digits are embedded among other numbers that serve as distractors. Correct hits and errors are counted for each trial and serve as the basis for scoring the test.	Baseline and up to day 8
Primary	Change in working memory and attention	Measured by the Paced Auditory Serial Addition Test (PASAT). Participants are read a series of numbers at specified time intervals. The participants are instructed to add the number to the preceding number and continue adding them together until the end of the trial. Four trials with 50 items each are administered with a 30 second break in between.	Baseline and up to day 8
Primary	Change in depression symptoms	Measured by the Beck Depression Inventory, 2nd Edition (BDI-II), which is a self-report questionnaire with 21 multiple choice items. The total score ranges from 0 to 63 with higher numbers indicating greater severity of depression symptoms.	Baseline and up to day 8
Primary	Change in anxiety symptoms	Measured by the State Trait Anxiety Inventory (STAI), which is a self-report questionnaire with 40 questions on a 4-point likert scale. The STAI measures two types of anxiety - state and trait scores. Higher scores are positively correlated with higher levels of anxiety.	Baseline and up to day 8
Secondary	Change in functional neuroimaging activation	Functional resting state sequences will be performed on the Phillips 3 tesla magnetic resonance (MR) research scanner.	Baseline and up to day 8
Secondary	Change in Symptom Score on the Sport Concussion Assessment Tool (SCAT3)	Obtained from the 22-item symptom evaluation included in the Sport Concussion Assessment Tool (SCAT3). The participant's present experience of each symptom is rated on a likert scale from 0 (none) to 6 (severe). The symptom score represents how many symptoms the participant endorses experiencing at a level greater than 0 (maximum 22 points).	Baseline and up to day 70
Secondary	Change in Symptom Severity on the Sport Concussion Assessment Tool (SCAT3)	Symptom evaluation included in the Sport Concussion Assessment Tool (SCAT3). The participant's present experience of each symptom is rated on a likert scale from 0 (none) to 6 (severe). The symptom severity represents the total summed severity ratings for all symptoms (maximum 132 points).	Baseline and up to day 70
Secondary	Change in sleep quality	Obtained from the Medical Outcomes Sleep Scale (MOS). This measure has 12 items and asks the participant to rate different aspects of their sleep experiences and sleep quality. The first two questions inquire about sleep times and the remaining questions utilize a likert scale ranging from 1 (all of the time) to 6 (none of the time).	Baseline and up to day 70
Secondary	Change in postural stability	The Balance Error Scoring System (BESS) will be used to measure postural stability, which is sensitive to deficits in balance following mild head injury. A modified version of (SCAT3) will be used. It includes three different stances, double leg, single leg, and tandem stance. A point is added for committing an error during the test interval and if the participant is unable to maintain his or her balance for more than 5 seconds, the trial is discontinued and maximum points are awarded. The total score ranges from 0 (better postural stability) to 30 (worse postural stability).	Baseline and up to day 70
Secondary	Change in depression symptoms	Measured by the Beck Depression Inventory, 2nd Edition (BDI-II), which is a self-report questionnaire with 21 multiple choice items. The total score ranges from 0 to 63 with higher numbers indicating greater severity of depression symptoms.	Baseline and up to day 70
Secondary	Change in anxiety symptoms	Measured by the State Trait Anxiety Inventory (STAI), which is a self-report questionnaire with 40 questions on a 4-point likert scale. The STAI measures two types of anxiety - state and trait scores. Higher scores are positively correlated with higher levels of anxiety.	Baseline and up to day 70