Traumatic Brain InjuryPhase 2NCT02226848
Effect of Recombinant Erythropoietin on Numbers of Circulating Endothelial Progenitor Cells in People With Persistent Symptoms During the Subacute Period After Traumatic Brain Injury
A Phase 2 study testing Erythropoeitin in people with Traumatic Brain Injury, run by National Institute of Neurological Disorders and Stroke (NINDS).
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Traumatic Brain Injury
- What is being tested?
- Erythropoeitin
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 15 Aug 2014to 31 May 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 24Show fewer
- 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
- Symptoms had their onset after trauma, or there is a significant worsening or preexisting symptoms after trauma.
- Ability to read, write, and speak English
- Ability to give consent by the participant himself
- 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.
Who cannot join
- 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
Show all 22Show fewer
- 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)
- ASA, Plavix or Aggrenox are not a contraindication
- 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 (EPO or placebo)
About this study
Official title: Effect of Administration of Recombinant Erythropoietin on Numbers of Circulating Endothelial Progenitor Cells in Patients With Persistent Symptoms During the Subacute Period After TBI
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.
Read more
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.
Read the detailed description
Objective
Traumatic brain injury (TBI) is the leading cause of death and disability in people under age 45 in industrialized countries 5;6. Significant numbers of US veterans from the wars in Iraq and Afghanistan return with TBI7. However, to date, there are no specific neuroprotective treatment options with proven clinical efficacy 8. 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) 4;9 and promotes angiogenesis and neovascularization after TBI. EPO also promotes neurogenesis and improves functional recovery in animals after experimental stroke10-12 and TBI.13;14 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.
Study Population
The study population will include 30 males and females with persistent post-concussive symptoms continuing up to 7 days after TBI. Participants will be military service members or civilians presenting as outpatients for clinical management of TBI or post-concussive symptoms at the Center for Neuroscience and Regenerative Medicine (CNRM)-affiliated hospitals. These include the Walter Reed National Military Medical Center (WRNMMC), Suburban Hospital (SH), and Washington Hospital Center (WHC).
Design
Participants will be referred to the NIH Clinical Center (CC) from participating hospitals or will be recruited by advertisements through CNRM Recruitment core to receive EPO or placebo. Telephone screening will be carried out to determine tentative eligibility. At the baseline visit, participants will be screened, consented and randomized 2:1 to receive either EPO or placebo with a dose of 40,000 IU EPO subcutaneously (s.c.) (n=20) once weekly for 4 weeks or placebo (n=10). Each participant will have 6 outpatient visits (visits 1-6) performed at the NIH CC. Placebo or active drug will be administered s.c. based on the randomization at visits 1-4; blood will be collected for EPC assays and safety laboratory measurements during each visit. Brain MRI and neuropsychological tests will be performed during visit 1 (before administering EPO or placebo), and visit 5 (one week after final drug administration) and visit 6 (6 months after study enrollment).
Outcome Measures
Primary outcome:
- . Effect of 4 weeks of EPO administration on numbers of circulating EPCs in patients with persistent symptoms during the subacute period after TBI (within subject comparison). Secondary outcomes:
- . Comparison of the change of numbers of circulating EPC s between EPO and placebo groups.
- . Effect of 4 weeks of EPO administration on MRI biomarkers of TBI recovery (such as CVR on hypercapnia and global and regional brain volumes by MRI).
- . Effect of 4 weeks of EPO administration on plasma biomarkers of angiogenesis and inflammation, such as stem cell factor (SCF), vascular endothelial growth factor (VEGF), stromal-derived factor (SDF-1 ); and matrix metalloproteinase-9 (MMP-9).
- . Effect of 4 weeks of placebo administration on numbers of circulating EPCs in patients with persistent symptoms during the subacute period after TBI. Tertiary outcome:
- . Relationship between EPC levels at baseline and after 4 weeks and neuropsychological performance following TBI.
- Conditions
- Traumatic Brain Injury
- Being tested
- Erythropoeitin
- Keywords
- Endothelial Progenitor Cells, Angiogenesis, Traumatic Brain Injury
- Medical subject headings
- Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ErythropoeitinDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Effect of 4 weeks of EPO administration on numbers of circulating EPCs in patients with persistent symptons during the subacute period after TBI.
Measured: 4 weeks
Secondary outcomes (4)
Safety of 4 weeks of EPO administration to TBI participants
Measured: 4 weeks
Effect of 4 weeks of EPO administration on MRI biomarkers of TBI recovery
Measured: 4 weeks
Effect of 4 weeks of EPO administration on biomarkers
Measured: 4 weeks
Relationship between EPC levels at baseline after 4 weeks and neuropsychological performance following TBI.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2014 (estimated)
- Study start15 Aug 2014
- Primary completion31 May 2017
- Study completion31 May 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Eric M Wassermann, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02226848
- Sponsor's protocol ID
- 140174
- Other IDs
- 14-N-0174
- Status last verified
- 31 May 2017
- First submitted
- 26 Aug 2014
- Last updated
- 5 Jul 2018
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Administration of Recombinant Erythropoietin on Numbers of Circulating Endothelial Progenitor Cells in Patients With Persistent Symptoms During the Subacute Period After TBI
- ClinicalTrials.gov ID
- NCT02226848
- Acronym / sponsor ID
- 140174
- Conditions
- Traumatic Brain Injury
- Keywords
- Endothelial Progenitor Cells, Angiogenesis, Traumatic Brain Injury
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 15 Aug 2014
- Primary completion
- 31 May 2017 (actual)
- Study completion
- 31 May 2017 (actual)
- First posted
- 27 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Objective
Traumatic brain injury (TBI) is the leading cause of death and disability in people under age 45 in industrialized countries 5;6. Significant numbers of US veterans from the wars in Iraq and Afghanistan return with TBI7. However, to date, there are no specific neuroprotective treatment options with proven clinical efficacy 8. 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) 4;9 and promotes angiogenesis and neovascularization after TBI. EPO also promotes neurogenesis and improves functional recovery in animals after experimental stroke10-12 and TBI.13;14 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.
Study Population
The study population will include 30 males and females with persistent post-concussive symptoms continuing up to 7 days after TBI. Participants will be military service members or civilians presenting as outpatients for clinical management of TBI or post-concussive symptoms at the Center for Neuroscience and Regenerative Medicine (CNRM)-affiliated hospitals. These include the Walter Reed National Military Medical Center (WRNMMC), Suburban Hospital (SH), and Washington Hospital Center (WHC).
Design
Participants will be referred to the NIH Clinical Center (CC) from participating hospitals or will be recruited by advertisements through CNRM Recruitment core to receive EPO or placebo. Telephone screening will be carried out to determine tentative eligibility. At the baseline visit, participants will be screened, consented and randomized 2:1 to receive either EPO or placebo with a dose of 40,000 IU EPO subcutaneously (s.c.) (n=20) once weekly for 4 weeks or placebo (n=10). Each participant will have 6 outpatient visits (visits 1-6) performed at the NIH CC. Placebo or active drug will be administered s.c. based on the randomization at visits 1-4; blood will be collected for EPC assays and safety laboratory measurements during each visit. Brain MRI and neuropsychological tests will be performed during visit 1 (before administering EPO or placebo), and visit 5 (one week after final drug administration) and visit 6 (6 months after study enrollment).
Outcome Measures
Primary outcome:
- . Effect of 4 weeks of EPO administration on numbers of circulating EPCs in patients with persistent symptoms during the subacute period after TBI (within subject comparison). Secondary outcomes:
- . Comparison of the change of numbers of circulating EPC s between EPO and placebo groups.
- . Effect of 4 weeks of EPO administration on MRI biomarkers of TBI recovery (such as CVR on hypercapnia and global and regional brain volumes by MRI).
- . Effect of 4 weeks of EPO administration on plasma biomarkers of angiogenesis and inflammation, such as stem cell factor (SCF), vascular endothelial growth factor (VEGF), stromal-derived factor (SDF-1 ); and matrix metalloproteinase-9 (MMP-9).
- . Effect of 4 weeks of placebo administration on numbers of circulating EPCs in patients with persistent symptoms during the subacute period after TBI. Tertiary outcome:
- . Relationship between EPC levels at baseline and after 4 weeks and neuropsychological performance following TBI.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- 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.
Key exclusion criteria (22 listed)
- Contraindication to EPO therapy:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Erythropoeitin | Drug | – |
Primary outcome
Effect of 4 weeks of EPO administration on numbers of circulating EPCs in patients with persistent symptons during the subacute period after TBI.
Time frame: 4 weeks
4 secondary outcomes
Safety of 4 weeks of EPO administration to TBI participants
Time frame: 4 weeks
Effect of 4 weeks of EPO administration on MRI biomarkers of TBI recovery
Time frame: 4 weeks
Effect of 4 weeks of EPO administration on biomarkers
Time frame: 4 weeks
Relationship between EPC levels at baseline after 4 weeks and neuropsychological performance following TBI.
Time frame: Baseline
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2018.
Related trials for Traumatic Brain Injury
Active, not recruitingObservational study
Transforming Research and Clinical Knowledge in Traumatic Brain Injury Epileptogenesis Project (TRACK-TBI EPI)
Traumatic Brain Injury, Post-traumatic Epilepsy
Enrolling by invitationPhase 1
Pilot Safety and Exploratory Efficacy of PSC-05 for the Treatment of Chronic Mild Traumatic Brain Injury
Mild Traumatic Brain Injury
RecruitingObservational study
Intracranial Pressure Monitoring in Moderate Traumatic Brain Injury
Moderate Traumatic Brain Injury
Not yet recruitingPhase 1
Nanopulse Laser Therapy
TBI (Traumatic Brain Injury)
RecruitingObservational study
Effect of Different Intravenous Fluids on Post-operative Chronic Subdural Hematoma Size and Recurrence
Chronic Subdural Hematoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eric M Wassermann, M.D. principal investigator
National Institute of Neurological Disorders and Stroke (NINDS)
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Erythropoeitin in people with Traumatic Brain Injury, run by National Institute of Neurological Disorders and Stroke (NINDS).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 5 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effect of 4 weeks of EPO administration on numbers of circulating EPCs in patients with persistent symptons during the subacute period after TBI. (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jul 2018.