Traumatic Brain InjuryPhase 2NCT01851083
Pediatric Autologous Bone Marrow Mononuclear Cells for Severe Traumatic Brain Injury
A Phase 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 2 sites in United States.
Trial summary
Pediatric severe traumatic brain injury (TBI) is the leading cause of death and disability in children ages 1-14 years old. There are no effective therapies to treat secondary brain injury and the post-injury response of CNS apoptosis and neuroinflammation. Read more about this study
- Who is it for?
- Ages 5 to 17 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?
- Yes, some participants may receive a placebo
- How many people
- 47 participants
- Where
- 2 sitesUnited States
- Study dates
- Aug 2013to 12 Oct 2020
- 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 5 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Between 5 and 17 years of age on the day of injury,
- Glasgow Coma Score (GCS) between 3 and 8, (best un-medicated post-resuscitation score during screening),
- Ability to obtain legally authorized representative (LAR) consent, and complete the BMMNC/Sham harvest and cell/placebo infusion within 48 hours of the initial injury,
- Ability to speak English or Spanish.
Who cannot join
- Known history of: a. previous brain injury, b. intellectual deficiency or psychiatric condition, defined as inability to independently function in a regular classroom that may invalidate our ability to assess post-injury changes in cognition or behavior (ADHD and/or other learning disabilities are NOT an exclusion), c. neurologic impairment and/or deficit, d. seizure disorder requiring anti-convulsant therapy, e. recently treated infection, f. renal disease or altered renal function (post-resuscitation serum creatinine > 1.5 mg/dL), g. hepatic disease or altered liver function (post-resuscitation, non-contusion related SGPT > 150 μ/L and/or T. Bilirubin >1.3 mg/dL), h. cancer, i. immunosuppression as defined by WBC < 3, 000 cells/ml at admission, j. HIV+, k. chemical or ETOH dependency, l. history of child abuse, m. premature birth (<37 weeks GA/2500 grams) resulting in cognitive/physical disabilities and/or developmental delay.
- Obliteration of perimesencephalic cistern on initial head CT/MRI suggesting prolonged hypoxic ischemic insult/herniation syndrome.
- Initial hospital ICP > 40 mm Hg.
- Hemodynamic instability at the time of screening defined as SBP <90 mmHg, ongoing fluid resuscitation and/or requirement for inotropic support to maintain MAP at or above normal for age - does not include CPP based inotropic support. IVF alone does not exclude from enrollment.
- Uncorrected coagulopathy at the time of bone marrow harvest defined as INR > 1.6, PTT > 38 sec; PLT< 100,000; Fibrinogen < 100 g/dL.
- Unstable pelvic fractures defined as requiring early operative fixation.
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- Pulmonary contusions defined as a chest x-ray with non-anatomic opacification and/or PaO2:FiO2 ratio < 250 associated with the mechanism of injury.
- Greater than AAST Grade 3 solid or hollow visceral injury of the abdomen and/or pelvis as diagnosed by CT or other imaging.
- Spinal cord injury diagnosed by CT/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.
- Positive pregnancy test, if applicable.
- Concurrent participation in an interventional drug/device research study.
- Unwillingness to return for follow-up visits.
- Contraindications to MRI.
- Penetrating brain injury.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
The University of Texas Health Science Center at Houston
Houston, Texas, 77030
Phoenix Children's Hospital I University of Arizona
Phoenix, Arizona, 85006
About this study
Official title: A Phase 2 Multicenter Trial of Pediatric Autologous Bone Marrow Mononuclear Cells (BMMNCs) for Severe Traumatic Brain Injury (TBI)
Pediatric severe traumatic brain injury (TBI) is the leading cause of death and disability in children ages 1-14 years old. There are no effective therapies to treat secondary brain injury and the post-injury response of CNS apoptosis and neuroinflammation. This study is a follow-up trial from a previously performed Phase I trial that demonstrated the safety and potential CNS structural preservation effect of intravenous autologous bone marrow mononuclear cells (BMMNC) after severe TBI in children. (Cox, 2011) The study is designed as a prospective, randomized, placebo controlled, blinded Phase 2 safety/biological activity study. The investigators hope to determine the effect of intravenous infusion of autologous BMMNCs on brain structure and neurocognitive/functional outcomes after severe TBI in children.
Read the detailed description
Study Design: Multicenter, randomized, blinded, placebo controlled, Bayesian adaptive dose escalation design.
Study Intervention: Single dose administered within 48 hours from time of injury. Controls will undergo a sham harvest and receive similarly labeled/external appearance and volume of 0.9% NaCl. BMMNC's will be harvested and undergo processing under cGMP conditions to obtain 6x10^6 cells/kg or 10x10^6 cells/kg weight. The cellular product/placebo will be infused within 48 hours of injury.
Safety Monitoring \& Follow-Up: Subjects will be monitored for infusion related toxicity post-infusion through hospital discharge and follow-up return study visits. Laboratory and imaging studies will be repeated at the 1, 6, and 12-month follow-up visits. A medical safety monitor (MSM) will review blinded SAE reports following post-infusion Day 14 for each subject in real time to ensure good clinical practice and to quickly identify safety concerns. The MSM will remain blinded to the treatment assignment, unless the NINDS appointed DSMB approves unblinding.
- Conditions
- Traumatic Brain Injury
- Being tested
- autologous bone marrow mononuclear cells, Placebo Infusion
- Keywords
- Traumatic Brain Injury, TBI, pediatric, acute, 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
BMMNC infusion of either 6x10^6 cells/kg or 10x10^6 cells/kg weight.
Placebo InfusionOther
Also called Saline Infusion
Placebo infusion of 0.9% Sodium Chloride
| Study group | Role | What they receive |
|---|---|---|
| autologous bone marrow mononuclear cells | Experimental | a bone marrow harvest will be performed, followed by a single intravenous infusion of autologous bone marrow mononuclear cells within 48 hours of injury. Receives: Biological: autologous bone marrow mononuclear cells |
| placebo infusion | Placebo comparator | a sham harvest will be performed, followed by a single intravenous placebo infusion within 48 hours of injury. Receives: Other: Placebo Infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
brain white matter and gray matter structural preservation on diffusion tensor magnetic resonance imaging (DTMRI)
DTMRI quantitative indices of both macro and microscopic integrity will be evaluated and compared to DTMRI of immediate post-injury treated and non-treated controls.
Measured: one year post infusion
Secondary outcomes (1)
CNS white matter and gray matter preservation in regions of interest and improves functional and neurocognitive deficits in children after TBI
Measured: one year post infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2013 (estimated)
- Study startAug 2013
- Primary completion16 Sep 2020
- Study completion12 Oct 2020
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 47 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
- NCT01851083
- Sponsor's protocol ID
- HSC-MS-13-0038
- Other IDs
- R01NS077963
- Status last verified
- Nov 2020
- First submitted
- 5 May 2013
- Last updated
- 20 Nov 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Multicenter Trial of Pediatric Autologous Bone Marrow Mononuclear Cells (BMMNCs) for Severe Traumatic Brain Injury (TBI)
- ClinicalTrials.gov ID
- NCT01851083
- Acronym / sponsor ID
- HSC-MS-13-0038
- Conditions
- Traumatic Brain Injury
- Keywords
- Traumatic Brain Injury, TBI, pediatric, acute, stem cells
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center, HoustonUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Aug 2013
- Primary completion
- 16 Sep 2020 (actual)
- Study completion
- 12 Oct 2020 (actual)
- First posted
- 10 May 2013 (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.
Pediatric severe traumatic brain injury (TBI) is the leading cause of death and disability in children ages 1-14 years old. There are no effective therapies to treat secondary brain injury and the post-injury response of CNS apoptosis and neuroinflammation. This study is a follow-up trial from a previously performed Phase I trial that demonstrated the safety and potential CNS structural preservation effect of intravenous autologous bone marrow mononuclear cells (BMMNC) after severe TBI in children. (Cox, 2011) The study is designed as a prospective, randomized, placebo controlled, blinded Phase 2 safety/biological activity study. The investigators hope to determine the effect of intravenous infusion of autologous BMMNCs on brain structure and neurocognitive/functional outcomes after severe TBI in children.
Detailed description
Study Design: Multicenter, randomized, blinded, placebo controlled, Bayesian adaptive dose escalation design.
Study Intervention: Single dose administered within 48 hours from time of injury. Controls will undergo a sham harvest and receive similarly labeled/external appearance and volume of 0.9% NaCl. BMMNC's will be harvested and undergo processing under cGMP conditions to obtain 6x10^6 cells/kg or 10x10^6 cells/kg weight. The cellular product/placebo will be infused within 48 hours of injury.
Safety Monitoring \& Follow-Up: Subjects will be monitored for infusion related toxicity post-infusion through hospital discharge and follow-up return study visits. Laboratory and imaging studies will be repeated at the 1, 6, and 12-month follow-up visits. A medical safety monitor (MSM) will review blinded SAE reports following post-infusion Day 14 for each subject in real time to ensure good clinical practice and to quickly identify safety concerns. The MSM will remain blinded to the treatment assignment, unless the NINDS appointed DSMB approves unblinding.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| autologous bone marrow mononuclear cells | Experimental | Biological: autologous bone marrow mononuclear cellsa bone marrow harvest will be performed, followed by a single intravenous infusion of autologous bone marrow mononuclear cells within 48 hours of injury. |
| placebo infusion | Placebo comparator | Other: Placebo Infusiona sham harvest will be performed, followed by a single intravenous placebo infusion within 48 hours of injury. |
Who may qualify
- Ages
- 5 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Between 5 and 17 years of age on the day of injury,
- Glasgow Coma Score (GCS) between 3 and 8, (best un-medicated post-resuscitation score during screening),
- Ability to obtain legally authorized representative (LAR) consent, and complete the BMMNC/Sham harvest and cell/placebo infusion within 48 hours of the initial injury,
- Ability to speak English or Spanish.
Key exclusion criteria (15 listed)
- Known history of: a. previous brain injury, b. intellectual deficiency or psychiatric condition, defined as inability to independently function in a regular classroom that may invalidate our ability to assess post-injury changes in cognition or behavior (ADHD and/or other learning disabilities are NOT an exclusion), c. neurologic impairment and/or deficit, d. seizure disorder requiring anti-convulsant therapy, e. recently treated infection, f. renal disease or altered renal function (post-resuscitation serum creatinine > 1.5 mg/dL), g. hepatic disease or altered liver function (post-resuscitation, non-contusion related SGPT > 150 μ/L and/or T. Bilirubin >1.3 mg/dL), h. cancer, i. immunosuppression as defined by WBC < 3, 000 cells/ml at admission, j. HIV+, k. chemical or ETOH dependency, l. history of child abuse, m. premature birth (<37 weeks GA/2500 grams) resulting in cognitive/physical disabilities and/or developmental delay.
- Obliteration of perimesencephalic cistern on initial head CT/MRI suggesting prolonged hypoxic ischemic insult/herniation syndrome.
- Initial hospital ICP > 40 mm Hg.
- Hemodynamic instability at the time of screening defined as SBP <90 mmHg, ongoing fluid resuscitation and/or requirement for inotropic support to maintain MAP at or above normal for age - does not include CPP based inotropic support. IVF alone does not exclude from enrollment.
- Uncorrected coagulopathy at the time of bone marrow harvest defined as INR > 1.6, PTT > 38 sec; PLT< 100,000; Fibrinogen < 100 g/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: BMMNCsBMMNC infusion of either 6x10^6 cells/kg or 10x10^6 cells/kg weight. | Biological | autologous bone marrow mononuclear cells |
| Placebo InfusionAlso: Saline InfusionPlacebo infusion of 0.9% Sodium Chloride | Other | placebo infusion |
Primary outcome
brain white matter and gray matter structural preservation on diffusion tensor magnetic resonance imaging (DTMRI)
Time frame: one year post infusion
DTMRI quantitative indices of both macro and microscopic integrity will be evaluated and compared to DTMRI of immediate post-injury treated and non-treated controls.
1 secondary outcome
CNS white matter and gray matter preservation in regions of interest and improves functional and neurocognitive deficits in children after TBI
Time frame: one year post infusion
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 20 Nov 2020.
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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
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 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 2 sites 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 15 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 20 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. Some participants in this study may receive a placebo. 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 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?
brain white matter and gray matter structural preservation on diffusion tensor magnetic resonance imaging (DTMRI) (time frame: one year 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 20 Nov 2020.