Effect of Recombinant Erythropoietin on Numbers of Circulating Endothelial Progenitor Cells in People With Persistent Symptoms During the Subacute Period After Traumatic Brain Injury

• Status: Withdrawn
• Trial end date: 2017-05-31
• Target enrollment: 0
• Participant gender: All

Summary

Background:

• Traumatic brain injury (TBI) injures blood vessels in the brain. Endothelial progenitor cells (EPCs) help the body form new blood vessels. The drug erythropoietin (EPO) helps the body make more blood cells and might help make blood vessels. Researchers want to see if EPO helps people with TBI.

Objective:

• To see whether erythropoietin increases the number of endothelial progenitor cells circulating in the blood and changes reactivity of brain vessels.

Eligibility:

• Adults age 18 70 who had a TBI 3 7 days ago and still have symptoms.

Design:

• Participants will be screened with medical history and blood tests. Vital signs will be taken.

• Visit 1:

• Medical history, physical exam, and blood sample.

• Neuropsychological tests of memory, attention, and thinking. These include written and spoken questions, tests on paper or computer, and simple actions.

• Magnetic resonance imaging (MRI) scan with carbon dioxide. Participants will lie on a table that slides in and out of a metal cylinder. For part of the scan, participants will wear a breathing mask like a snorkel and wear a nose clip.

• Study drug or placebo injection under the skin of the arm, leg, or buttock.

• Visits 2, 3, and 4 will be 1 week apart.

• Blood sample.

• Review of TBI symptoms and any drug side effects.

• Study drug or placebo injection under the skin.

• Visit 5 will be 1 week after visit 4. Visit 6 will be 6 months after participants start the study.

• Blood sample.

• Review of TBI symptoms and any drug side effects.

• Neuropsychological tests.

• MRI with carbon dioxide.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)
• Treatments: Epoetin Alfa

Criteria

• INCLUSION CRITERIA:

1. Age 18 - 70 years, inclusive

2. History of having sustained a TBI greater than or equal to 3 days and less than or equal to 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 (either CT or MRI)

3. Persistent post-concussive symptoms, according to the DSM-IV Research Criteria for Post- Concussional Disorder.

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 preexisting symptoms after trauma.

4. Ability to read, write, and speak English

5. Ability to give consent by the participant himself

6. Willingness of women of childbearing potential to use effective contraception during this study and until 2 weeks after they have completed the study drug (EPO or placebo).

Effective methods of contraception for this study include:

• hormonal contraception (birth control pills, injected hormones or vaginal ring),

• intrauterine device,

• barrier methods (condom or diaphragm) combined with spermicide,

• surgical sterilization (hysterectomy, tubal ligation), or vasectomy in a partner.

EXCLUSION CRITERIA:

1. 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

2. Use of EPO one month prior to the randomization

3. Suspicion of a coagulation disorder associated with bleeding (PTT>45 or INR>1.7, spontaneously out of normal range)

4. 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

5. History of heart disease or heart attack, congestive heart failure, stroke, venous thromboembolism.

6. History of disorders that predispose to coagulation (e.g. polycythemia vera, essential thrombocytosis, or thrombotic thrombocytopenic purpura).

7. Uncontrolled hypertension, defined as above 140/90 mm Hg in three measurements in two separate visits despite antihypertensive therapy. Antihypertensive therapy is allowed, including agents such as thiazide diuretics, ACE inhibitors, beta-blockers, calcium channel blockers, alpha-blockers, or a centrally acting alpha agonists.

8. Known malignant conditions, e.g., melanoma, breast, brain, lung tumor or prostate cancer

9. Terminal medical diagnosis consistent with survival < 1 year

10. Planned surgical procedure during duration of the study (if emergency surgery needed, EPO administration will be stopped, but the patient will remain in the study according to the intention to treat principles).

11. Current use of Coumadin or other blood thinners (e.g. Pradaxa, Heparin, Lovenox)

ASA, Plavix or Aggrenox are not a contraindication

12. Any history of previous deep venous thrombosis (DVT), pulmonary embolization (PE), or other thromboembolic event

13. Current participation in other interventional clinical trial

14. Current use of iron supplements

15. Evidence of penetrating brain injury

16. Contraindication to MRI scanning

17. 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 (EPO or placebo)