ExercisePhase 1/2NCT01294332
Effect of Aerobic Exercise Training on Cardiorespiratory Function in Patients With Traumatic Brain Injury
A Phase 1/2 study testing Aerobic Exercise Training in people with Exercise and Fatigue, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.
Trial summary
Background: Many people who have traumatic brain injury (TBI) have low levels of physical fitness. Low physical fitness causes severe fatigue that reduces the ability to perform routine daily activities, and may also cause increased depression, anxiety, or sadness. Read more about this study
- Who is it for?
- Ages 21 to 45 years
- Conditions the study is for
- Exercise, Fatigue, Physical Fitness
- What is being tested?
- Aerobic Exercise Training
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 26 May 2011to 11 Feb 2014
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Subjects eligible for participation in this research study must meet the following inclusion criteria:
- Diagnosis of non-penetrating mild, moderate, or severe TBI
- Injury occurred at least 6 months prior to enrollment
- Age 21-45 years
- Physically inactive as identified by a physician.
- Able to stand and walk on a treadmill independently and safely without assistance
Show all 9Show fewer
- Able to follow the study protocol
- Fluent in English and able to provide informed consent
- Willing and safely able to forego starting or changing an exercise program or treatments that would potentially alter cardiorespiratory capacity or ability to exercise and/or treatment for mood disorders
Who cannot join
- Subjects are not eligible for participation in this research study if any of the following medical conditions that would impair aerobic capacity or the ability to engage in physical activity exist, including diseases of the cardiovascular (other than hypertension controlled by medication to below 140/90 mmHg), pulmonary, neurological, metabolic, or musculoskeletal systems such as:
- Diagnosis or history of ischemic heart disease, including those with CABG and PTCA
- Dilated or hypertrophic cardiomyopathy
- Non-idiopathic cardiomyopathy
- Uncontrolled hypertension, defined as a resting blood pressure above 140/90 mmHg
- Diagnosis or history of right or left-sided heart failure or pulmonary hypertension
Show all 18Show fewer
- Diagnosis or history of restrictive or obstructive lung disease
- Diagnosis or history of stroke
- Type I or Type II Diabetes Mellitus
- Diagnosis of chronic kidney disease, chronic liver disease, acute kidney injury or acute liver failure
- Metastatic cancer active within the previous five years
- Mitochondrial disease
- On medications that would influence aerobic capacity, the ability to adapt to exercise training, or treadmill performance such as beta blockers or antiretroviral therapy
- Active substance abuse including ETOH
- Ongoing tobacco use (any use within the past six months)
- Medical or Psychological instability such that the subject could not reasonably be expected to fulfill the study requirements
- Pregnancy
- BMI greater than 40 kg/m(2)
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Effect of Aerobic Exercise Training on Cardiorespiratory Fitness in Patients With Traumatic Brain Injury
Background:
- Many people who have traumatic brain injury (TBI) have low levels of physical fitness. Low physical fitness causes severe fatigue that reduces the ability to perform routine daily activities, and may also cause increased depression, anxiety, or sadness. Aerobic exercise, such as treadmill walking or running, improves physical fitness in most people and may also decrease fatigue and improve mood. However, more information is needed to determine if exercise improves these conditions in people who have TBI.
Read more
Objectives:
- To examine the effect of an aerobic treadmill walking exercise program on physical fitness, fatigue, and mood in people with TBI.
Eligibility:
- Individuals between 21 and 45 years of age who had a nonpenetrating traumatic brain injury at least 6 months before participating; able to understand oral and written English language, give informed consent and sign a consent form; are physically inactive (including activities related to both job and recreation); and are able to stand and walk on a treadmill safely without help.
Design:
- This study requires 4 testing visits and 36 exercise visits over 14 weeks.
- The first and third testing visits will last about 4 hours and the second and final testing visits will take about 2 hours.
- Testing visits will consist of a medical history and physical examination, completion of questionnaires (about fatigue, daily physical activity, sleep quality, mood, and overall quality of life), tests of thinking and a treadmill exercise test.
- Participants will have treadmill exercise training 3 days per week for 12 weeks. Each session includes a check-in, warm-up, treadmill walking at the training heart rate, and cool-down. Thirty-two of the sessions will last for about 1 hour, and four of the sessions will include questionnaires to fill out and will last about one-and-a-half hours.
- After completing the exercise training program, participants will have a final testing visit to complete the questionnaires (about fatigue, daily physical activity, sleep quality, mood, and overall quality of life), tests of thinking and a treadmill exercise test.
Read the detailed description
Objective
The broad objective of this exploratory project is to inform clinical studies and trials on the use of aerobic exercise training (AET) as an intervention for improving cardiorespiratory fitness in patients with traumatic brain injury (TBI). AET-induced adaptation of cardiorespiratory fitness and fatigue severity will be characterized, and time-course for changes in mood reactivity will be determined. We hypothesize that 1) AET will improve both cardiorespiratory fitness and fatigue severity 2) mood will at first worsen in response to AET but that mood reactivity will then decrease at some point during the intervention, and 3) AET will not impair overall cognitive performance, but that the specific cognitive performance areas of attention and concentration will improve with AET.
Study Population
Thirty-six adult subjects with a clinical diagnosis of non-penetrating TBI (mild, moderate, and severe) will be enrolled. Subjects will be recruited from NIH, affiliated hospitals/clinics, and in the community.
Design
This is a pilot study with a pre-experimental, test-intervention-retest design. Cardiorespiratory fitness, fatigue severity, cognitive performance, and changes in mood reactivity will be measured at baseline. The subjects will then participate in a 12-week treadmill exercise training intervention protocol known to improve cardiorespiratory fitness in the general population. Following the 12 weeks of AET, cardiorespiratory fitness, fatigue severity, and cognitive performance will be retested and compared to baseline. Changes in mood reactivity will be assessed monthly.
Outcome Measures
AET-induced change in cardiorespiratory fitness as measured by peak oxygen consumption (VO2) is the primary outcome measure and will be measured by pulmonary gas exchange analysis during treadmill exercise tolerance testing. A submaximal, continuous work rate test will also be used to measure the ability of the cardiorespiratory system to meet the energy demands of work over time (VO2 on-kinetics). The Fatigue Severity Scale (FSS) is the principal measurement tool for the fatigue outcome variable. FSS scores will be interpreted in relation to information from the Medical Outcomes Study 36-Item Short Form (MOS-36SF), Becks Depression Inventory (BDI), The Pittsburgh Sleep Quality Index (PSQI), International Physical Activity Questionnaire (IPAQ) and the Profile of Mood States Short Form (POMS-SF). Cognitive performance will be tested and interpreted compared to norms by the Finger Tapping Test (FTT), the Trail Making Test (TMT) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Change in mood reactivity will be measured as the difference in the POMS-SF scores before and after 30 minutes of recovery. The outcome variable for time-course related change in mood reactivity is the week of onset for significant improvement in mood reactivity.
- Conditions
- Exercise, Fatigue, Physical Fitness, Traumatic Brain Injury
- Being tested
- Aerobic Exercise Training
- Keywords
- Cognition, TBI, Mood, Aerobic Exercise Training, Cardiorespiratory Fitness
- Medical subject headings
- Motor Activity, Fatigue, Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aerobic Exercise TrainingOther
supervised exercise on the treadmill at target heart rate range for 12 weeks, 3 times a week for 30 minutes.
| Study group | Role | What they receive |
|---|---|---|
| Exercise | Experimental | Aerobic exercise performed for 12 weeks Receives: Other: Aerobic Exercise Training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in peak oxygen consumption
The peak VO2 as measured by gas exchange during a cardiopulmonary exercise test to volitional exhaustion.
Measured: Pre and post
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2011 (estimated)
- Study start26 May 2011
- Primary completion31 Dec 2013
- Study completion11 Feb 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ExerciseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institutes of Health Clinical Center (CC)
- Sponsor type
- US National Institutes of Health
- Collaborators
- Center for Neuroscience and Regenerative Medicine (CNRM)
- Responsible party
- Sponsor
- Investigators
- Leighton Chan, M.D., Principal investigator, National Institutes of Health Clinical Center (CC)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01294332
- Sponsor's protocol ID
- 110088
- Other IDs
- 11-CC-0088
- Status last verified
- 9 Dec 2025
- First submitted
- 10 Feb 2011
- Last updated
- 8 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Chin LMK, Chan L, Drinkard B, Keyser RE. Oxygen uptake on-kinetics before and after aerobic exercise training in individuals with traumatic brain injury. Disabil Rehabil. 2019 Dec;41(24):2949-2957. doi: 10.1080/09638288.2018.1483432. Epub 2018 Jun 30.
PubMed 29961351
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Aerobic Exercise Training on Cardiorespiratory Fitness in Patients With Traumatic Brain Injury
- ClinicalTrials.gov ID
- NCT01294332
- Acronym / sponsor ID
- 110088
- Conditions
- Exercise, Fatigue, Physical Fitness, Traumatic Brain Injury
- Keywords
- Cognition, TBI, Mood, Aerobic Exercise Training, Cardiorespiratory Fitness
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- National Institutes of Health Clinical Center (CC)US National Institutes of Health
- Collaborators
- Center for Neuroscience and Regenerative Medicine (CNRM)
- Study start
- 26 May 2011 (actual)
- Primary completion
- 31 Dec 2013 (actual)
- Study completion
- 11 Feb 2014 (actual)
- First posted
- 11 Feb 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Many people who have traumatic brain injury (TBI) have low levels of physical fitness. Low physical fitness causes severe fatigue that reduces the ability to perform routine daily activities, and may also cause increased depression, anxiety, or sadness. Aerobic exercise, such as treadmill walking or running, improves physical fitness in most people and may also decrease fatigue and improve mood. However, more information is needed to determine if exercise improves these conditions in people who have TBI.
Objectives:
- To examine the effect of an aerobic treadmill walking exercise program on physical fitness, fatigue, and mood in people with TBI.
Eligibility:
- Individuals between 21 and 45 years of age who had a nonpenetrating traumatic brain injury at least 6 months before participating; able to understand oral and written English language, give informed consent and sign a consent form; are physically inactive (including activities related to both job and recreation); and are able to stand and walk on a treadmill safely without help.
Design:
- This study requires 4 testing visits and 36 exercise visits over 14 weeks.
- The first and third testing visits will last about 4 hours and the second and final testing visits will take about 2 hours.
- Testing visits will consist of a medical history and physical examination, completion of questionnaires (about fatigue, daily physical activity, sleep quality, mood, and overall quality of life), tests of thinking and a treadmill exercise test.
- Participants will have treadmill exercise training 3 days per week for 12 weeks. Each session includes a check-in, warm-up, treadmill walking at the training heart rate, and cool-down. Thirty-two of the sessions will last for about 1 hour, and four of the sessions will include questionnaires to fill out and will last about one-and-a-half hours.
- After completing the exercise training program, participants will have a final testing visit to complete the questionnaires (about fatigue, daily physical activity, sleep quality, mood, and overall quality of life), tests of thinking and a treadmill exercise test.
Detailed description
Objective
The broad objective of this exploratory project is to inform clinical studies and trials on the use of aerobic exercise training (AET) as an intervention for improving cardiorespiratory fitness in patients with traumatic brain injury (TBI). AET-induced adaptation of cardiorespiratory fitness and fatigue severity will be characterized, and time-course for changes in mood reactivity will be determined. We hypothesize that 1) AET will improve both cardiorespiratory fitness and fatigue severity 2) mood will at first worsen in response to AET but that mood reactivity will then decrease at some point during the intervention, and 3) AET will not impair overall cognitive performance, but that the specific cognitive performance areas of attention and concentration will improve with AET.
Study Population
Thirty-six adult subjects with a clinical diagnosis of non-penetrating TBI (mild, moderate, and severe) will be enrolled. Subjects will be recruited from NIH, affiliated hospitals/clinics, and in the community.
Design
This is a pilot study with a pre-experimental, test-intervention-retest design. Cardiorespiratory fitness, fatigue severity, cognitive performance, and changes in mood reactivity will be measured at baseline. The subjects will then participate in a 12-week treadmill exercise training intervention protocol known to improve cardiorespiratory fitness in the general population. Following the 12 weeks of AET, cardiorespiratory fitness, fatigue severity, and cognitive performance will be retested and compared to baseline. Changes in mood reactivity will be assessed monthly.
Outcome Measures
AET-induced change in cardiorespiratory fitness as measured by peak oxygen consumption (VO2) is the primary outcome measure and will be measured by pulmonary gas exchange analysis during treadmill exercise tolerance testing. A submaximal, continuous work rate test will also be used to measure the ability of the cardiorespiratory system to meet the energy demands of work over time (VO2 on-kinetics). The Fatigue Severity Scale (FSS) is the principal measurement tool for the fatigue outcome variable. FSS scores will be interpreted in relation to information from the Medical Outcomes Study 36-Item Short Form (MOS-36SF), Becks Depression Inventory (BDI), The Pittsburgh Sleep Quality Index (PSQI), International Physical Activity Questionnaire (IPAQ) and the Profile of Mood States Short Form (POMS-SF). Cognitive performance will be tested and interpreted compared to norms by the Finger Tapping Test (FTT), the Trail Making Test (TMT) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Change in mood reactivity will be measured as the difference in the POMS-SF scores before and after 30 minutes of recovery. The outcome variable for time-course related change in mood reactivity is the week of onset for significant improvement in mood reactivity.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Exercise | Experimental | Other: Aerobic Exercise TrainingAerobic exercise performed for 12 weeks |
Who may qualify
- Ages
- 21 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Subjects eligible for participation in this research study must meet the following inclusion criteria:
- Diagnosis of non-penetrating mild, moderate, or severe TBI
- Injury occurred at least 6 months prior to enrollment
- Age 21-45 years
- Physically inactive as identified by a physician.
Key exclusion criteria (18 listed)
- Subjects are not eligible for participation in this research study if any of the following medical conditions that would impair aerobic capacity or the ability to engage in physical activity exist, including diseases of the cardiovascular (other than hypertension controlled by medication to below 140/90 mmHg), pulmonary, neurological, metabolic, or musculoskeletal systems such as:
- Diagnosis or history of ischemic heart disease, including those with CABG and PTCA
- Dilated or hypertrophic cardiomyopathy
- Non-idiopathic cardiomyopathy
- Uncontrolled hypertension, defined as a resting blood pressure above 140/90 mmHg
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Aerobic Exercise Trainingsupervised exercise on the treadmill at target heart rate range for 12 weeks, 3 times a week for 30 minutes. | Other | Exercise |
Primary outcome
Change in peak oxygen consumption
Time frame: Pre and post
The peak VO2 as measured by gas exchange during a cardiopulmonary exercise test to volitional exhaustion.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2026.
- Derived from this study: PubMed 29961351Chin LMK, Chan L, Drinkard B, Keyser RE. Oxygen uptake on-kinetics before and after aerobic exercise training in individuals with traumatic brain injury. Disabil Rehabil. 2019 Dec;41(24):2949-2957. doi: 10.1080/09638288.2018.1483432. Epub 2018 Jun 30.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
Related trials for Exercise
RecruitingPhase 2
Neurovascular Regulation During Exercise in Humans With Chronic Kidney Disease: Sympatholysis in CKD
Chronic Kidney Disease
Not yet recruiting
Combined Versus Multicomponent Training in People With Chronic Kidney Disease Stages 3a and 3b
Chronic Kidney Disease Stage 3A, Chronic Kidney Disease Stage 3B
Recruiting
Understanding the Feasibility of a Co-designed Pre-radiotherapy Exercise Programme - A Single-arm Study
Lung Cancer
Not yet recruiting
Integrated Core Stability Exercises and Yoga Program on Premenstrual Syndrome
Premenstrual Syndrome
RecruitingPhase 2
Spironolactone for Pulmonary Arterial Hypertension
Pulmonary Arterial Hypertension
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Leighton Chan, M.D. principal investigator
National Institutes of Health Clinical Center (CC)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Aerobic Exercise Training in people with Exercise and Fatigue, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in peak oxygen consumption (time frame: Pre and post). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01294332, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2026.