Traumatic Brain InjuryPhase 1/2NCT01575470
Treatment of Severe Adult Traumatic Brain Injury Using Bone Marrow Mononuclear Cells
A Phase 1/2 study testing autologous bone marrow mononuclear cells in people with Traumatic Brain Injury, run by The University of Texas Health Science Center, Houston at 1 site in United States.
Trial summary
The purpose of this study is to determine if bone marrow harvest, BMMNC separation, and re-infusion in adults with acute severe TBI is safe and will improve functional outcome. 12/09/2015 Update: The study is closed to new enrollment and all follow-up visits have been completed. Data analysis is underway. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Traumatic Brain Injury
- What is being tested?
- autologous bone marrow mononuclear cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2012to May 2015
- Phase
- Phase 1/2
- 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 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Between 18 and 55 years of age on the day of injury;
- Hospital admission Glasgow Coma Score between 5 and 8;
- Initial injury occurring less than 24 hours prior to consent;
- Ability to speak English.
Who cannot join
- Known history of:
- brain injury,
- psychiatric disorder,
- neurological impairment and/or deficit
- seizure disorder requiring anti-convulsant therapy
- recently treated infection
Show all 26Show fewer
- renal disease or altered renal function
- hepatic disease or altered liver function
- cancer
- substance abuse of positive urine drug screen at admission
- immunosuppression
- HIV
- Obliteration of perimesencephalic cistern on initial head CT suggesting prolonged hypoxic ischemic insult
- Initial hospital ICP > 40mm Hg
- Hemodynamic instability at the time of consent defined as ongoing fluid resuscitation and/or requirement for inotropic support to maintain MAP at or above normals for age - does not include CPP based inotropic support
- Uncorrected coagulopathy at the time of bone marrow harvest defined as INR >1.6, PTT >36 sec, PLT < 100,000, Fibrinogen < 100g/dL
- Unstable pelvic fractures defined as requiring operative fixation to manage
- Pulmonary contusions defined as a chest x-ray with non-anatomic opacification and/or PaO2:FIO2 ratio < 250 associated with the mechanism or injury
- Greater than AAST Grade I solid or hollow visceral injury of the abdomen and/or pelvis as diagnosed by CT or other imaging
- Spinal cord injury as diagnosed by CT or MR imaging or clinical findings
- Persistent hypoxia defined as SaO2 < 94% for > 30 minutes occurring at any time from hospital admission to time of consent
- Weight > 300 lbs
- Any contraindication to MRI (including being too large to fit into the MRI)
- Positive urine pregnancy test
- Participation in a concurrent intervention study
- Unwillingness to return for follow-up visits
Trial locations and contacts
1 site in 1 country.
United States1 site
The University of Texas Health Science Center at Houston
Houston, Texas, 77030
About this study
The purpose of this study is to determine if bone marrow harvest, BMMNC separation, and re-infusion in adults with acute severe TBI is safe and will improve functional outcome.
12/09/2015 Update: The study is closed to new enrollment and all follow-up visits have been completed. Data analysis is underway.
Read the detailed description
Traumatic brain injury (TBI) contributes to 50% of all trauma deaths. The mortality rate for adults following severe TBI (Glasgow Coma Scale < 9) is estimated to be 33%. There is currently no therapy to reverse the primary injury associated with TBI. Over the past 10 years there has been a growing body of literature supporting the use of various progenitor cell types to treat acute neurological injuries such as TBI and stroke. Neural stem cells (adult and embryonic), mesenchymal stromal and multipotent adult progenitor cells, and bone marrow mononuclear cells (from which MSC and MAPCs are derived) have all shown efficacy in pre-clinical models of TBI/stroke through various mechanisms; however, few groups believe that true neural replacement and integration are the putative mechanisms involved in the observed efficacy. More likely is that the progenitor cell populations are modifying the regional response to injury (inflammatory/reparative vs. regenerative), resulting in improved functional outcomes. Our primary hypothesis is that bone marrow mononuclear cell (BMMNC) autologous transplantation after TBI is safe (harvest and infusion related toxicity) after TBI. Our secondary hypothesis is that functional outcomes measures will improve after BMMNC infusion, (3) BMMNC infusion will reduce BBB permeability, (4) BMMNC is neuroprotective and preserves grey matter and white matter volumes after TBI.
Patients, ages18 to 55 years old, admitted to Memorial Hermann Hospital Trauma Center with Glasgow Coma Scores (GCS) of 5 to 8 will be screened. Those patients meeting inclusion/exclusion criteria (or their Legal Authorized Representative [LAR]) will be offered consent to participate. This is a dose-escalation study consisting of 4 cohorts including a control group (5 subjects/cohort). The first five subjects will not undergo the bone marrow harvest procedure; though they will be followed and treated the same as the other study participants and complete all follow-up procedures. Subjects 6-10 will receive the lowest dose target of 6X106 mononuclear cells/kilogram body weight. Subjects 11-15 will receive 9x106 mononuclear cells/kilogram body weight, and lastly Subjects 16-20 will receive 12X106 mononuclear cells/kilogram body weight. The study is NOT powered to detect functional measures of efficacy. However, estimates can be made regarding potential treatment effect sizes to allow rational power analyses for the follow-on Phase II study. This study should determine if bone marrow harvest, BMMNC separation, and reinfusion is safe in adults with acute, severe TBI.
- Conditions
- Traumatic Brain Injury
- Being tested
- autologous bone marrow mononuclear cells
- Keywords
- Traumatic Brain Injury, TBI, stem cells
- 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.
autologous bone marrow mononuclear cellsBiological
Also called BMMNCs
bone marrow harvest (5ml/kg of body weight) performed within 36 hours of injury, followed by single intravenous infusion of bone marrow mononuclear cells.
| Study group | Role | What they receive |
|---|---|---|
| bone marrow mononuclear cells | Experimental | a bone marrow harvest will be performed within 36 hours of injury followed by a single intravenous infusion of autologous bone marrow mononuclear cells (BMMNCs) Receives: Biological: autologous bone marrow mononuclear cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
neurological events (seizures, changes in Glasgow coma score [GCS], cerebral vascular accident [CVA})
Measured: 12 hours post product infusion up to 21 days post infusion
Secondary outcomes (3)
infectious morbidity
Measured: up to 21 days post infusion
global functional status per the GOS-E
the Glasgow Outcome Scale-Extended (GOS-E) will be administered to assess global functional status (consciousness, independence, work status, return of lifestyle)
Measured: up to 6 months post injury/treatment
global functioning per the Disability Rating Scale
the Disability Rating Scale (DRS) will be administered which measures level of arousal, cognitive ability related to activities of daily living, motor response, feeding, toileting, grooming and employability
Measured: up to 6 months post injury/treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2012 (estimated)
- Study startMar 2012
- Primary completionMay 2015
- Study completionMay 2015
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 The University of Texas Health Science Center, HoustonThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Charles Cox, The University of Texas Health Science Center, Houston
- Investigators
- Charles S Cox, Jr., M.D., Principal investigator, The University of Texas Health Science Center, Houston
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01575470
- Sponsor's protocol ID
- HSC-MS-11-0477
- Other IDs
- Award No. W81XWH-11-1-0460
- Status last verified
- Jul 2016
- First submitted
- 6 Apr 2012
- Last updated
- 13 Jul 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Severe Adult Traumatic Brain Injury Using Bone Marrow Mononuclear Cells
- ClinicalTrials.gov ID
- NCT01575470
- Acronym / sponsor ID
- HSC-MS-11-0477
- Conditions
- Traumatic Brain Injury
- Keywords
- Traumatic Brain Injury, TBI, stem cells
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center, HoustonUniversity, hospital or other
- Study start
- Mar 2012
- Primary completion
- May 2015 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 11 Apr 2012 (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.
The purpose of this study is to determine if bone marrow harvest, BMMNC separation, and re-infusion in adults with acute severe TBI is safe and will improve functional outcome.
12/09/2015 Update: The study is closed to new enrollment and all follow-up visits have been completed. Data analysis is underway.
Detailed description
Traumatic brain injury (TBI) contributes to 50% of all trauma deaths. The mortality rate for adults following severe TBI (Glasgow Coma Scale < 9) is estimated to be 33%. There is currently no therapy to reverse the primary injury associated with TBI. Over the past 10 years there has been a growing body of literature supporting the use of various progenitor cell types to treat acute neurological injuries such as TBI and stroke. Neural stem cells (adult and embryonic), mesenchymal stromal and multipotent adult progenitor cells, and bone marrow mononuclear cells (from which MSC and MAPCs are derived) have all shown efficacy in pre-clinical models of TBI/stroke through various mechanisms; however, few groups believe that true neural replacement and integration are the putative mechanisms involved in the observed efficacy. More likely is that the progenitor cell populations are modifying the regional response to injury (inflammatory/reparative vs. regenerative), resulting in improved functional outcomes. Our primary hypothesis is that bone marrow mononuclear cell (BMMNC) autologous transplantation after TBI is safe (harvest and infusion related toxicity) after TBI. Our secondary hypothesis is that functional outcomes measures will improve after BMMNC infusion, (3) BMMNC infusion will reduce BBB permeability, (4) BMMNC is neuroprotective and preserves grey matter and white matter volumes after TBI.
Patients, ages18 to 55 years old, admitted to Memorial Hermann Hospital Trauma Center with Glasgow Coma Scores (GCS) of 5 to 8 will be screened. Those patients meeting inclusion/exclusion criteria (or their Legal Authorized Representative [LAR]) will be offered consent to participate. This is a dose-escalation study consisting of 4 cohorts including a control group (5 subjects/cohort). The first five subjects will not undergo the bone marrow harvest procedure; though they will be followed and treated the same as the other study participants and complete all follow-up procedures. Subjects 6-10 will receive the lowest dose target of 6X106 mononuclear cells/kilogram body weight. Subjects 11-15 will receive 9x106 mononuclear cells/kilogram body weight, and lastly Subjects 16-20 will receive 12X106 mononuclear cells/kilogram body weight. The study is NOT powered to detect functional measures of efficacy. However, estimates can be made regarding potential treatment effect sizes to allow rational power analyses for the follow-on Phase II study. This study should determine if bone marrow harvest, BMMNC separation, and reinfusion is safe in adults with acute, severe TBI.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| bone marrow mononuclear cells | Experimental | Biological: autologous bone marrow mononuclear cellsa bone marrow harvest will be performed within 36 hours of injury followed by a single intravenous infusion of autologous bone marrow mononuclear cells (BMMNCs) |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Between 18 and 55 years of age on the day of injury;
- Hospital admission Glasgow Coma Score between 5 and 8;
- Initial injury occurring less than 24 hours prior to consent;
- Ability to speak English.
Key exclusion criteria (26 listed)
- Known history of:
- Obliteration of perimesencephalic cistern on initial head CT suggesting prolonged hypoxic ischemic insult
- Initial hospital ICP > 40mm Hg
- Hemodynamic instability at the time of consent defined as ongoing fluid resuscitation and/or requirement for inotropic support to maintain MAP at or above normals for age - does not include CPP based inotropic support
- Uncorrected coagulopathy at the time of bone marrow harvest defined as INR >1.6, PTT >36 sec, PLT < 100,000, Fibrinogen < 100g/dL
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 |
|---|---|---|
| autologous bone marrow mononuclear cellsAlso: BMMNCsbone marrow harvest (5ml/kg of body weight) performed within 36 hours of injury, followed by single intravenous infusion of bone marrow mononuclear cells. | Biological | bone marrow mononuclear cells |
Primary outcome
neurological events (seizures, changes in Glasgow coma score [GCS], cerebral vascular accident [CVA})
Time frame: 12 hours post product infusion up to 21 days post infusion
3 secondary outcomes
infectious morbidity
Time frame: up to 21 days post infusion
global functional status per the GOS-E
Time frame: up to 6 months post injury/treatment
global functioning per the Disability Rating Scale
Time frame: up to 6 months post injury/treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2016.
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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.
Charles S Cox, Jr., M.D. principal investigator
The University of Texas Health Science Center, Houston
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing autologous bone marrow mononuclear cells in people with Traumatic Brain Injury, run by The University of Texas Health Science Center, Houston at 1 site in United States.
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 4 inclusion and 26 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: finished, as of the sponsor's last update on 13 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
neurological events (seizures, changes in Glasgow coma score [GCS], cerebral vascular accident [CVA}) (time frame: 12 hours post product infusion up to 21 days post infusion). 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 13 Jul 2016.