Effect of Aerobic Exercise Training on Cardiorespiratory Function in Patients With Traumatic Brain Injury

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.

• INCLUSION CRITERIA:

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
• 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

Exclusion criteria

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
• 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)