Effect of Recombinant Erythropoietin on Numbers of Circulating Endothelial Progenitor Cells in Subacute TBI

Summary

* Traumatic brain injury (TBI) is the leading cause of death and disability in people under age 45 in industrialized countries. Significant numbers of US veterans from the wars in Iraq and Afghanistan return with TBI. However, to date, there are no specific neuroprotective treatment options with proven clinical efficacy.
* Erythropoietin (EPO) is approved by the FDA to treat anemia and has comprehensive preclinical data supporting its neuroprotective and neuroregenerative efficacy following traumatic (TBI) and a wide range of other acquired brain insults. Injury to small and medium-sized cerebral blood vessels is a well recognized consequence of TBI. EPO increases production of endothelial progenitor cells (EPCs) and promotes angiogenesis and neovascularization after TBI. EPO also promotes neurogenesis and improves functional recovery in animals after experimental stroke and TBI. Neovascularization is coupled with neurogenesis, and augmentation of both processes by EPO may result in lessened cognitive deficits. Neovascularization by EPO may prevent post-traumatic deficits in cerebrovascular reactivity (CVR), which can be measured noninvasively using magnetic resonance imaging (MRI).
* This proposal is for a randomized, placebo-controlled pilot clinical trial designed to obtain data on the effects of EPO in humans with persistent post-concussive symptoms after TBI. The primary objective is to evaluate effect of 4 week administration of recombinant erythropoietin on numbers of circulating endothelial progenitor cells in patients with persistent symptoms during the subacute period after TBI. This information will guide the design of a future definitive study.

Conditions

• Traumatic Brain Injury

Interventions

DRUG

Erythropoietin

This is a double blind randomized placebo-cotrolled study. Randomization and blinding will be done by the NIH Pharmacy. Participants and study staff will be blinded as to group assignment.Participants randomized into the placebo group will receive placebo once weekly for 4 weeks. In total, 10 participants will be randomized in this group. Participants randomized into the experimental group will receive active drug. In total, 20 participants will be randomized in this group. A clinic nurse or physician will administer the study drug, EPO or placebo, to the study participants at the Clinical Center. The study drug is administered by injection under the skin in the arm, leg, or buttock.

Sponsors & Collaborators

• National Institutes of Health (NIH)

  collaborator NIH

• Uniformed Services University of the Health Sciences

  lead FED

Principal Investigators

• Ramon Diaz-Arrastia, MD, PhD · Uniformed Services University of the Health Sciences

• Eric Wassermann, MD · National Institutes of Health (NIH)

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-09-30

Primary Completion

2016-06-30

Completion

2016-12-31

Countries

• United States

Study Locations