Post-Traumatic Brain Injury (Post-TBI) Fatigue and Its Treatment

Purpose: The purpose of this study is to examine the efficacy of the drug modafinil as a
treatment for fatigue post TBI.

Background: After TBI, fatigue is one of the most common complaints, as documented in our
work and that of many other researchers. People with TBI experience fatigue that seems to
them out of proportion to whatever work they are doing or effort they are making. Fatigue
after TBI is associated with decreased participation in normal activities in the community
and has been linked to depression.

Need for Research: Research on use of drugs to treat post-TBI fatigue is inadequate. While
studies of fatigue in people with other chronic conditions suggest that modafinil helps
relieve fatigue and has fewer side effects than some other drugs used in treating fatigue,
the use of modafinil has not yet been tested in people with TBI.

Current and Future Research Activity: More than 100 men and women volunteers who complain of
post-TBI fatigue will be randomly assigned to a 4-week period of taking modafinil or a
placebo. At the beginning and end of the study, the severity of their fatigue and associated
symptoms (e.g., cognitive function, mood, pain, daytime sleepiness, sleep quality, health
status) will be assessed, as well as their participation in activities and perceived quality
of life. It is hypothesized that modafinil will reduce the symptoms of fatigue and will
increase level of activity and perceived quality of life to a significantly greater extent
than will the placebo.

Inclusion Criteria:

- Individuals who sustained a TBI with a documented loss of consciousness or evidence of a
TBI on neuroimaging studies and who are at least 12 months post-injury, who complain of
fatigue and who have scores of 22 or above on the Barroso Fatigue Scale will be eligible
to participate in this study. Subjects must not meet criteria for alcohol or substance
abuse using the Structured Clinical Interview for DSM-IV (SCID) for at least six months
prior to study enrollment.

Exclusion Criteria:

- Diagnosis of chronic neurological disease (including Lyme disease), narcolepsy, current
infectious disease, chronic fatigue syndrome, fibromyalgia, anemia, hypothyroidism not
adequately controlled with medication, blood pressure greater 150/100 mm Hg, or clinically
significant major systemic disease. In addition, individuals taking medications which are
known to cause fatigue will be excluded from participation in the study.