This is a prospective, randomized, placebo-controlled study about Cyclosporine A (CSP) and
traumatic brain injury (TBI). Cyclosporine A is a drug already marketed and available for
other diseases, but is not approved by the Food and Drug Administration for treatment of
traumatic brain injury. The effect of Cyclosporine A on chemicals produced following brain
injury is being determined using doses no larger than those used for patients having organ
transplant. It is also being given for a much shorter time period (3 days). It is not know if
side effects seen in patients taking cyclosporine A will occur when it is given for only 3
days. It is not known if patients with brain injury that are treated with cyclosporine A will
have side effects like those seen in organ transplant patients.
The purpose of this research study is to measure the chemicals produced by the brain after it
is injured and also if Cyclosporine A treatment changes these chemicals. By doing this study,
the investigators hope to learn if cyclosporine A therapy helps patients with this injury.
The research procedures will happen at the University of Kentucky (UK) Chandler Medical
Center. The study will last for the first 7 days while the participant is admitted to UK
Medical Center, or until they are released. Participants will not be asked to stay longer in
the hospital for this research study.
Participants in this study will receive all therapies currently available for treatment of
severe brain injury. Each participant will be assigned randomly (by chance) to either placebo
(a substance without active drug) or cyclosporine A treatment. Neither the participant nor
any of the study personnel will know what study treatment has been assigned to the
If assigned to the cyclosporine A treatment group (study drug) participants will be
continuously administered the study drug through a tube placed into the vein. A placebo will
be given to participants assigned to the placebo group.
Blood and cerebrospinal fluid will be collected at the following time points (12, 24, 36, 48,
60 and 72 hours) for research purposes. These tests will help us understand the participant's
ability to make red and white blood cells to fight infection, how well their kidneys
function, how well their liver functions, and triglyceride/cholesterol levels.
Cerebrospinal fluid will only be collected from participants who have a drain catheter placed
as part of their routine care.
Daily blood collections will occur so the investigators can measure how much of the study
drug is present, to assess the body chemicals from the brain and also for safety. Blood
samples will be collected by using an already placed line through a vein or artery, or by
puncturing the skin with a needle. The chemicals will be measured daily in the urine and also
any fluid draining from the line placed into the head for medical management for up to 7
Any unexpected events (side effects) possibly caused by cyclosporine A will be noted and
medically managed by the physician. The investigators will be notified when there is need for
After up to three days of continuous dosing, the study drug will be stopped, but the
participant will continue to be carefully monitored for up to 7 days, or until they are
Participants will receive the usual treatment for severe traumatic brain injury in addition
to receiving the cyclosporine A treatment or placebo.
- Participant is between the ages of 18 and 65
- Participant speaks and understands English
- CT Scan evidence of severe TBI
- Post resuscitation GSC 4-8 with at least one reactive pupil
- motor score of greater than 5
- Study medication will be administered within 8 hours injury
- Participant received high dose systemic corticosteroids, such as Methylprednisolone
>15 mg/kg or equivalent,
- Participant has a known allergy to cyclosporine A,
- Participant is pregnant,
- Participant is less than 18 years of age or greater than 65 years of
- Participant has a history of kidney problems, history of stroke or spinal cord injury,
- Participant has a history of cardiovascular disease, or use of immunosuppressive
therapy in the last three months,
- Participant has a history of malignant tumors unless they have been in remission at
least five years.
- Participant has an active infection
- Participant has taken part in another investigational trial within the last 30 days.