Effect of Recombinant Erythropoietin on Numbers of Circulating Endothelial Progenitor Cells in Subacute TBI (TBI-EPO)

This is an interventional prevention trial for Traumatic Brain Injury focused on measuring Traumatic brain injury, Endothelial progenitor cells, Cerebrovascular reactivity, Angiogenesis Read More

Inclusion Criteria:

• Age 18 - 70 years, inclusive

• History of having sustained a TBI > 3 days and < 7 days prior to enrollment. This evidence will be any one of the following:

  1. GCS 3 - 12 on first presentation to medical attention
  2. Post-traumatic amnesia > 24 hours
  3. TBI-related abnormality on neuroimaging

• Persistent post-concussive symptoms

  1. Three of more of the following symptoms, which started shortly after the trauma and persist for at least up to the time of enrollment:

     • Fatigueability
     • Disordered sleep
     • Headache
     • Vertigo or dizziness
     • Irritability or aggression
     • Anxiety, depression, or affective instability
     • Changes in personality (e.g., social or sexual inappropriateness)
     • Apathy or lack of spontaneity
  2. Symptoms had their onset after trauma, or there is a significant worsening or pre-existing symptoms after trauma.
• Ability to give consent by the participant himself
• Willingness of women of childbearing potential to use effective contraception during this

Exclusion Criteria:

• Contraindication to EPO therapy:

  1. Known allergy to EPO, hypersensitivity to mammalian cell-derived products, or hypersensitivity to albumin
  2. Serum hemoglobin > 16 g/dL in a male patient or > 14 g/dL in a female patient; or a platelet count > 400,000/mm3 or serum hemoglobin < 10 g/dL in either a male or female patient
  3. liver or kidney disease; the former will be operationally defined as a serum bilirubin > 4 mg/dL, alkaline phosphatase (AP) > 250 U/L, aspartate aminotransferase (SGOT, AST) > 150 U/L, alanine aminotransferase (SGPT, ALT) >150 U/L, or Moderately decreased GFR 30-59 ml/min/1.73m2
  4. Pregnancy or lactating; note that a negative pregnancy test will be required if the patient is a female of childbearing potential
• Use of EPO one month prior to the randomization
• Suspicion of a coagulation disorder associated with bleeding (PTT>45 or INR>1.7, spontaneously out of normal range)
• Pre-existing and active major disabling psychiatric disorder (e.g., schizophrenia or bipolar disorder), or other neurological disease (epilepsy, multiple sclerosis, developmental disorder) not related to TBI
• History of heart disease or heart attack, congestive heart failure, stroke, venous thromboembolism.
• History of disorders that predispose to coagulation (e.g. polycythemia vera, essential thrombocytosis, or thrombotic thrombocytopenic purpura).
• Uncontrolled hypertension, defined as above 140/90 mm Hg in three measurements in two separate visits despite antihypertensive therapy.
• Known malignant conditions, e.g., melanoma, breast, brain, lung tumor or prostate cancer
• Terminal medical diagnosis consistent with survival < 1 year
• Planned surgical procedure during duration of the study
• Current use of Coumadin or other blood thinners (e.g. Pradaxa, Heparin, Lovenox).
• Any history of previous deep venous thrombosis (DVT), pulmonary embolization (PE), or other thromboembolic event
• Current participation in other interventional clinical trial
• Current use of iron supplements
• Evidence of penetrating brain injury
• Contraindication to MRI scanning
• No adherence to use of effective method of contraception for females of childbearing potential for time from enrollment to the study until 2 weeks after completion of the study drug