Characterization of Fatigue in Military Personnel With Traumatic Brain Injuries
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03998358|
Recruitment Status : Not yet recruiting
First Posted : June 26, 2019
Last Update Posted : January 17, 2020
People who have had a traumatic brain injury (TBI) often experience fatigue. Fatigue is the feeling tired all the time. Researchers want to learn more about how TBI and fatigue are related.
To better understand fatigue after TBI in active duty military and veterans.
Active duty service members or veterans ages 25-40 who have sustained at least 1 TBI more than 6 months but less than 5 years ago
Participants will be screened with:
- Medical history
- Physical exam
- Blood and urine tests
Participants will have Visit 1 the same day as screening. This will include questionnaires and interviews. These will be about their fatigue, quality of life, and health.
Participants will wear an activity monitor on their wrist and complete a sleep diary for 7 days at home.
Participants will have Visit 2: They will stay in the clinic for 2 nights. The visit will include:
- Tests of memory, attention, and thinking
- Placement of intravenous (IV) line: A needle will guide a thin plastic tube into the participant s arm vein.
- 2 overnight sleeps tests: Participants brain waves will be recorded while they sleep. Small electrodes will be placed on the scalp. Monitors will be placed on the skin. These will measure breathing, heart rate, and movement. Blood will be drawn overnight through the IV line.
- Optional hydrocortisone stimulation test: Participants will receive the hormone through the IV line. Blood will be drawn through the IV line 5 times over 1 hour.
- Optional MRI: Participants will lie in a machine. This machine is a metal cylinder that takes pictures of the brain.
|Condition or disease|
|Traumatic Brain Injury Neurobehavioral Manifestation Sleep Disorder Fatigue|
Objective: Traumatic brain injury (TBI) is the signature injury of recent wars. Fatigue is a pervasive and debilitating consequence of TBIs, experienced by up to 80% of military personnel following TBI. If present greater than 6 months post-injury, fatigue is classified as chronic and may hinder recovery and affect return to service in military personnel. However, the pathophysiology through which TBI results in fatigue symptomology remains unclear. This protocol will examine several pathways that have been hypothesized to underlie the association between TBI and fatigue including; sleep disturbances, neuroendocrine and mitochondrial abnormalities. Sleep disturbances and fatigue overlap and frequently co-occur after TBI. However, to date no published studies have investigated the association between objectively measured sleep and fatigue following TBI with and without significant fatigue in military personnel. The second pathway involves dysfunction of the neuroendocrine system, which participates in the regulation of sleep states, circadian function, and attention. Deficits in neuroendocrine function, including putative changes in crucial neuronal populations in the hypothalamus and in somatotrophic cells of the anterior pituitary will result in changes in regulatory hormones such as growth hormone (GH). Evidence suggests that disruptions to GH may be associated with fatigue, however, current findings are mixed. The final pathway may be through mitochondrial dysfunction. Early results from multiple fields have shown that decreased mitochondrial markers have been associated with fatigue, however few studies have looked at these predicted associations in TBI populations. It is evident that further research is needed to examine the relationships between TBI and fatigue. Thus, this protocol aims to identify the pathways associated with TBI and fatigue. Findings from this protocol may lead to novel targets for intervention and reduction of fatigue symptomology following TBI.
Aim: To identify factors that are associated with the persistence of fatigue symptomology, at or greater than 6 months post TBI.
Protocol population: Up to 74 military personnel will be recruited into this protocol. All participants will have experienced their most recent TBI >= 6 months and <= 5 years prior to protocol participation.
Design: We will compare military personnel who have sustained a TBI with and without subsequent fatigue symptomology. This protocol will have two visits, one outpatient and one inpatient to NIH which include:
Screening Visit: All participants will undergo a clinical evaluation of TBI history, fatigue, and complete self-report questionnaires. Participants will also be given an actigraph and sleep diary to take home and complete.
Sleep Visit: All participants will undergo two, consecutive, overnight polysomnography (PSG) tests, which includes one night of serial blood sampling to examine endocrine function and neuropeptide release. Over the two days, participants may also complete an optional hydrocortisone stimulation test and their mitochondrial respiratory profile will be assessed. During this in-patient stay, all participants will undergo neurocognitive testing and have an opportunity to undergo magnetic resonance imaging (MRI).
|Study Type :||Observational|
|Estimated Enrollment :||74 participants|
|Official Title:||Characterization of Fatigue in Military Personnel With Traumatic Brain Injuries|
|Estimated Study Start Date :||January 22, 2020|
|Estimated Primary Completion Date :||June 30, 2022|
|Estimated Study Completion Date :||June 30, 2022|
TBI patients with significant fatigue as calculated by a score of >= 5.5 on the Fatigue Severity Scale
TBI patients without significant fatigue as calculated by a score of < 5.5 on the Fatigue Severity Scale
- Determine differences in objective sleep measures determined by actigraphy and PSG data in military personnel with and without fatigue following a TBI. [ Time Frame: Study completion ]The PSG will be scored by the Clinical Center Sleep Service within two weeks and will generate the following data: -Sleep Onset Latency (SOL): Is a measurement of the time taken to fall asleep from the time the lights were turned off. On average, this process takes approximately 20 minutes. - Sleep efficiency (SE): the number of minutes of sleep divided by the number of minutes in bed. Normal is approximately 85 to 90% or higher, but in-lab values are often less. -Sleep stages; From this information each 30-second epoch is scored as "awake" or one of 4 sleep stages: 1, 2, 3, and REM or Rapid Eye Movement sleep. Stages 1-3 are together called non-REM sleep. Non-REM sleep is distinguished from REM sleep, which is altogether different. Delta power for each stage will also be examined. The primary outcome being assessed will be delta power of SWS and REM between fatigued and non-fatigued.
- Determine differences in neurobehavioral and neurocognitive functioning in military personnel with and without fatigue following a TBI. [ Time Frame: Study Completion ]Determine differences in neurobehavioral and neurocognitive functioning in military personnel with and without fatigue following a TBI
- Describe differences in plasma concentration levels of neuroendocrine proteins during overnight hours in military personnel with and without fatigue following a TBI. [ Time Frame: Study Completion ]Describe differences in plasma concentration levels of neuroendocrine proteins during overnight hours in military personnel with and without fatigue following a TBI.
- Determine differences in neuroendocrine and mitochondrial functionality in military personnel with and without fatigue following a TBI. [ Time Frame: Study Completion ]Determine differences in neuroendocrine and mitochondrial functionality in military personnel with and without fatigue following a TBI.
- Compare group differences in level of fatigue between the two protocol visits. [ Time Frame: Study Completion ]Compare group differences in level of fatigue between the two protocol visits.
- Determine differences in perceived sleep quality (PSQI) and actual sleep quality as measured by actigraphy. [ Time Frame: Study Completion ]Determine differences in perceived sleep quality (PSQI) and actual sleep quality as measured by actigraphy.
- Compare volume of hypothalamus, attentional + arousal regions of interest as well as fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity and white matter integrity using DTI in military personnel w and w/out fatigue following ... [ Time Frame: Study Completion ]Compare volume of hypothalamus, attentional + arousal regions of interest as well as fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity and white matter integrity using DTI in military personnel w and w/out fatigue following a TBI.
- Determine if there are group differences in actigraphically measured sleep, light, and physical activity. [ Time Frame: Study Completion ]Determine if there are group differences in actigraphically measured sleep, light, and physical activity.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03998358
|Contact: Mary V Ley, R.N.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||Jessica Gill, Ph.D.||National Institute of Nursing Research (NINR)|