Effect of Exercise Training on Physical, Cognitive, and Behavioral Function in People With TBI

Traumatic Brain Injury (TBI) Clinical Trial

Official title:

Effect of Exercise Training on Physical, Cognitive and Behavioral Function in Patients With Traumatic Brain Injury

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02504866
• Other study ID #: 150164
• Secondary ID: 15-CC-0164
• Status: Terminated
• Phase: N/A
• Start date: December 15, 2016
• Est. completion date: February 6, 2020

Study information

• Verified date: February 2023
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Background:

• Traumatic brain injury (TBI) often causes problems with moving and balance, and thinking and emotions. Exercise can improve these things in people with other brain damage. Researchers want to look at the effect of exercise on these things in people with TBI.

Objectives:

• To study how head injuries affect the brain. To study if exercise can help some symptoms in people with TBI. These include problems thinking, balancing, and moving, and depression or anxiety.

Eligibility:

• People age between 18 and 79

• Had a non-penetrating TBI at least 12 months ago

• Are physically inactive, but can stand and walk without help

Design:

• Participants will be screened with medical history, physical exam, and blood and urine tests. They may have a balance test.

• Participants will be assigned to a high-intensity or a lower-intensity exercise program.

• The study is 6 months long. There will be 3 months with exercise on an elliptical machine and 3 months without exercise.

• Participants will exercise for 30 minutes on an elliptical machine, 3 days per week for 3 months.

• Participants will also have 3 outpatient testing visits lasting approximately 8 hours, once every 3 months. This visit will include:

• Blood tests

• Tests for memory, attention, and thinking

• Tests of walking and balance

• Questionnaires

• An MRI: they will lie in a machine that takes pictures of their brain, while breathing regular air and air with more carbon dioxide

• Test of physical fitness

Description:

Objective

The broad objective of this study is to examine the effects of moderate and more intense aerobic exercise as an intervention on cognitive performance, physical functioning and health-related quality of life in patients with chronic (more than 12 months post-injury) traumatic brain injury (TBI). Importantly, structural and biological brain changes will be measured to examine whether functional outcomes are related to exercise-induced adaptations. It is hypothesized that in the chronic phase of persons with TBI, there will be improved: 1) cognitive function, 2) physical fitness and fatigue severity, 3) motor performance and balance, and 4) mood and depressive symptoms, in those that performed the exercise intervention compared to a control group. It is also hypothesized that these functional improvements will be related to exercise intensity, improved cortical connectivity, dopamine transmission gene scores, and blood biomarkers related to neuro and angio-genesis.

Study Population

80 ambulatory adults with non-penetrating TBI will be enrolled. We will also enroll up to 20 healthy volunteers as a comparison group for some of the outcome measures. Subjects will be recruited from NIH, affiliated hospitals/clinics and the community

Design

Healthy volunteers will have a limited assessment that includes brain imaging, blood draw for genetic testing, and a subset of the cognitive and behavioral testing at a single time-point. All subjects with TBI will perform baseline assessments including cognitive and behavioral performance, brain imaging, fitness, motor and balance testing, and selected blood and genetic testing. Thereafter, subjects with TBI will be randomized to either a waitlist control, or one of two exercise conditions: 1) 30 minutes at a fast pace, moderate-intensity (rapid-resistive exercise; RET); 2) 30 minutes at higher-intensity (aerobic exercise; AET). Both exercise groups will perform the exercise on an elliptical trainer 3 times a week, for a session duration of 45 minutes including warm-up and cool-down. The RET group will focus on rapid reciprocal motion with minimal resistance, while the AET group will exercise at an elevated intensity known to produce an aerobic effect. After 12 weeks, all groups will repeat the baseline assessments (3 month follow-up). Following this assessment, the waitlist control group will be randomized to either RET or AET and the exercise groups will cease formal supervised exercise sessions. A third assessment visit will be performed after an additional 12 weeks (6 month follow-up).

Outcome Measures

Cognitive performance will be tested and interpreted compared to norms. Performance on motor and balance tasks will be assessed with the Smart Balance Measurement System and the GAITRite System. Physical fitness will be determined by peak oxygen consumption and aerobic threshold as measured by pulmonary gas exchange during an exercise tolerance test on the treadmill. Structural brain volumes will be determined by magnetic resonance imaging (MRI) and cortical connectivity will be quantified using resting state functional MRI and Diffusion Tensor Imaging (DTI) to evaluate integrity of and changes in white matter tracts in response to exercise and compared to healthy volunteers. Blood will be collected to quantify the presence of biomarkers (such as VEGF, BDNF and IGF-1) and dopamine transmission. Other self-reported measures of quality of life, fatigue severity, depression and sleep quality would also be collected, and compared to healthy volunteers.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 20
• Est. completion date: February 6, 2020
• Est. primary completion date: February 4, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

• INCLUSION CRITERIA:

Inclusion criteria for those with TBI:

1. Ages 18 to 79 inclusive

2. Diagnosis of non-penetrating TBI

3. Injury occurred at least 12 months prior to enrollment

4. Physically inactive as identified by a physician

5. Able to stand and walk independently and safely without any assistance

6. Able to follow the study protocol

7. Fluent in English and able to provide informed consent

Inclusion criteria for healthy volunteers:

1. Ages 18 to 79 inclusive

2. Physically inactive as identified by a physician

3. Fluent in English

EXCLUSION CRITERIA:

Exclusion criteria for those with TBI:

1. History of exercise intolerance

2. History of heart disease

3. History of pulmonary disease, other than controlled, non-exercise-induced asthma

4. History of uncontrolled diabetes

5. Uncontrolled hypertension, defined as a resting blood pressure > 140/90 mmHg

6. On medications that would influence aerobic capacity or treadmill performance such as beta blockers or antiretroviral therapy

7. Active substance abuse including ETOH

8. Presence of an injury to any extremity, or other medical condition that would affect motor function or the ability to perform the assessment or the exercise program, specifically balance problems due to vestibulopathy

9. Unable to refrain from smoking at least 4 hours prior to exercise testing sessions

10. Medical or psychological instability such that the subject could not reasonably be expected to fulfill the study requirements

11. Pregnancy

12. BMI >40 kg/M(2) due to the limits of the treadmill, elliptical machine and MRI scanner

13. Planning to make a change in medication or therapy during the enrollment period with the goal of improving mood, cognitive function or motor function

14. Have any of the following contraindications to having an MRI scan:

1. A ventriculo-peritoneal shunt

2. Have claustrophobia and not comfortable in small enclosed spaces

3. Have metal that would make an MRI scan unsafe such as: cardiac pacemaker, insulin infusion pump, implanted drug infusion devise, cochlear or ear implant, transdermal medication patch (nitroglycerine), any metallic implants or objects, body piercing that cannot be removed, bone or joint pin, screw, nail, plate, wire sutures or surgical staples, shunts, cerebral aneurysms clips, shrapnel or other metal embedded (such as from war wounds or accidents or previous work in metal fields or machines that may have left any metallic fragments in or near your eyes).

4. Excessive startle reaction to or fear of loud noises

Exclusion criteria for healthy volunteers:

1. History or presence of cardiopulmonary or respiratory disease

2. History or presence of other disease of the neurologic, metabolic, or renal systems

3. Active substance abuse including ETOH

4. Pregnancy

5. BMI >40 kg/m2

6. Medical or psychological instability such that the subject could not reasonably be expected to fulfill the study requirements

7. Have any contraindications to having an MRI scan

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Traumatic Brain Injury (TBI)

Intervention

Other:
• Vigorous exercise
Exercise training of vigorous intensity
• Light to moderate exercise
Exercise training of light to moderate intensity

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center	Bethesda	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
National Institutes of Health Clinical Center (CC)	Center for Neuroscience and Regenerative Medicine (CNRM)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Chin LM, Chan L, Woolstenhulme JG, Christensen EJ, Shenouda CN, Keyser RE. Improved Cardiorespiratory Fitness With Aerobic Exercise Training in Individuals With Traumatic Brain Injury. J Head Trauma Rehabil. 2015 Nov-Dec;30(6):382-90. doi: 10.1097/HTR.0000000000000062. — View Citation

Chin LM, Keyser RE, Dsurney J, Chan L. Improved cognitive performance following aerobic exercise training in people with traumatic brain injury. Arch Phys Med Rehabil. 2015 Apr;96(4):754-9. doi: 10.1016/j.apmr.2014.11.009. Epub 2014 Nov 26. — View Citation

Damiano DL, Zampieri C, Ge J, Acevedo A, Dsurney J. Effects of a rapid-resisted elliptical training program on motor, cognitive and neurobehavioral functioning in adults with chronic traumatic brain injury. Exp Brain Res. 2016 Aug;234(8):2245-52. doi: 10.1007/s00221-016-4630-8. Epub 2016 Mar 30. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Cognitive Function as Measured by Trail Making Test Part B (TMT-B)	Trail Making Test (TMT) is a neuropsychological assessment of visual conceptual and visual motor tracking (involves motor speed and attention functions). Trail Making Test Part B (TMT-B) is associated with executive functioning and involves drawing a line connecting alternating numbers and letters in sequence (i.e., 1-A-2-B and so on). The time to complete the test is recorded. The time taken to complete the test was converted into standardized T-scores, representing a mean of 50 and a standard deviation of 10. Higher T-scores mean less cognitive deficits. The change in cognitive function was reported as the change in TMT-B T-scores across the 12 weeks (post minus pre intervention).	Before (pre) and after (post) 12 weeks intervention

External Links

•   NIH Clinical Center Detailed Web Page