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

NCT02226848 | Withdrawn Phase 2

• 2 other identifiers: 14017414-N-0174
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Traumatic Brain Injury

Keywords

Endothelial Progenitor Cells; Angiogenesis; Traumatic Brain Injury

Outcome Measures

Primary Outcomes (1)

• Effect of 4 weeks of EPO administration on numbers of circulating EPCs in patients with persistent symptons during the subacute period after TBI.

  4 weeks

Secondary Outcomes (4)

• Safety of 4 weeks of EPO administration to TBI participants

  4 weeks

• Effect of 4 weeks of EPO administration on MRI biomarkers of TBI recovery

  4 weeks

• Effect of 4 weeks of EPO administration on biomarkers

  4 weeks

• Relationship between EPC levels at baseline after 4 weeks and neuropsychological performance following TBI.

  Baseline

Interventions

Erythropoeitin DRUG

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 - 70 years, inclusive
• 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:
• GCS 3 - 12 on first presentation to medical attention
• Post-traumatic amnesia \> 24 hours
• TBI-related abnormality on neuroimaging (either CT or MRI)
• Persistent post-concussive symptoms, according to the DSM-IV Research Criteria for Post- Concussional Disorder.
• 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

You may not qualify if:

• Contraindication to EPO therapy:
• Known allergy to EPO, hypersensitivity to mammalian cell-derived products, or hypersensitivity to albumin
• 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
• 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
• 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. 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.
• 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 (if emergency surgery needed, EPO administration will be stopped, but the patient will remain in the study according to the intention to treat principles).
• Current use of Coumadin or other blood thinners (e.g. Pradaxa, Heparin, Lovenox)

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

MeSH Terms

Conditions

Brain Injuries, Traumatic

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Study Officials

• Eric M Wassermann, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2014
• First Posted: August 27, 2014
• Study Start: August 15, 2014
• Primary Completion: May 31, 2017
• Study Completion: May 31, 2017
• Last Updated: July 5, 2018

Record last verified: 2017-05-31