- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01851083
Pediatric Autologous Bone Marrow Mononuclear Cells for Severe Traumatic Brain Injury
A Phase 2 Multicenter Trial of Pediatric Autologous Bone Marrow Mononuclear Cells (BMMNCs) for Severe Traumatic Brain Injury (TBI)
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
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Arizona
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Phoenix, Arizona, United States, 85006
- Phoenix Children's Hospital I University of Arizona
-
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Texas
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Houston, Texas, United States, 77030
- The University of Texas Health Science Center at Houston
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: autologous bone marrow mononuclear cells
a bone marrow harvest will be performed, followed by a single intravenous infusion of autologous bone marrow mononuclear cells within 48 hours of injury.
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BMMNC infusion of either 6x10^6 cells/kg or 10x10^6 cells/kg weight.
Other Names:
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Placebo Comparator: placebo infusion
a sham harvest will be performed, followed by a single intravenous placebo infusion within 48 hours of injury.
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Placebo infusion of 0.9% Sodium Chloride
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
brain white matter and gray matter structural preservation on diffusion tensor magnetic resonance imaging (DTMRI)
Time Frame: one year post infusion
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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.
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one year post infusion
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
one year post infusion
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Infusional toxicity safety evaluations
Time Frame: 7 days post-infusion
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Murray Score and liver function tests
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7 days post-infusion
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Collaborators and Investigators
Investigators
- Principal Investigator: Charles S Cox, Jr., M.D., The University of Texas Health Science Center, Houston
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- HSC-MS-13-0038
- R01NS077963 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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