Pediatric Autologous Bone Marrow Mononuclear Cells for Severe Traumatic Brain Injury

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2016 by The University of Texas Health Science Center, Houston
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Charles Cox, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier:
NCT01851083
First received: May 5, 2013
Last updated: April 20, 2016
Last verified: April 2016
  Purpose
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.

Condition Intervention Phase
Traumatic Brain Injury
Biological: autologous bone marrow mononuclear cells
Other: Placebo Infusion
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2 Multicenter Trial of Pediatric Autologous Bone Marrow Mononuclear Cells (BMMNCs) for Severe Traumatic Brain Injury (TBI)

Resource links provided by NLM:


Further study details as provided by The University of Texas Health Science Center, Houston:

Primary Outcome Measures:
  • brain white matter and gray matter structural preservation on diffusion tensor magnetic resonance imaging (DTMRI) [ Time Frame: one year post infusion ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Infusional toxicity safety evaluations [ Time Frame: 7 days post-infusion ] [ Designated as safety issue: Yes ]
    Murray Score and liver function tests


Estimated Enrollment: 50
Study Start Date: August 2013
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Biological: autologous bone marrow mononuclear cells
BMMNC infusion of either 6x10^6 cells/kg or 10x10^6 cells/kg weight.
Other Name: BMMNCs
Placebo Comparator: placebo infusion
a sham harvest will be performed, followed by a single intravenous placebo infusion within 48 hours of injury.
Other: Placebo Infusion
Placebo infusion of 0.9% Sodium Chloride
Other Name: Saline Infusion

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.

  Eligibility

Ages Eligible for Study:   5 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Between 5 and 17 years of age on the day of injury,
  2. Glasgow Coma Score (GCS) between 3 and 8, (best un-medicated post-resuscitation score during screening),
  3. 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,
  4. Ability to speak English or Spanish.

Exclusion Criteria:

  1. 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.
  2. Obliteration of perimesencephalic cistern on initial head CT/MRI suggesting prolonged hypoxic ischemic insult/herniation syndrome.
  3. Initial hospital ICP > 40 mm Hg.
  4. 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.
  5. Uncorrected coagulopathy at the time of bone marrow harvest defined as INR > 1.6, PTT > 38 sec; PLT< 100,000; Fibrinogen < 100 g/dL.
  6. Unstable pelvic fractures defined as requiring early operative fixation.
  7. Pulmonary contusions defined as a chest x-ray with non-anatomic opacification and/or PaO2:FiO2 ratio < 250 associated with the mechanism of injury.
  8. Greater than AAST Grade 3 solid or hollow visceral injury of the abdomen and/or pelvis as diagnosed by CT or other imaging.
  9. Spinal cord injury diagnosed by CT/MR imaging or clinical findings.
  10. Persistent hypoxia defined as SaO2 < 94% for > 30 minutes occurring at any time from hospital admission to time of consent.
  11. Positive urine pregnancy test.
  12. Concurrent participation in an interventional drug/device research study.
  13. Unwillingness to return for follow-up visits.
  14. Contraindications to MRI.
  15. Penetrating brain injury.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01851083

Contacts
Contact: Steven C Kosmach, MSN, RN, CCRC 713-500-7329 steven.kosmach@uth.tmc.edu

Locations
United States, Arizona
Phoenix Children's Hospital I University of Arizona Recruiting
Phoenix, Arizona, United States, 85006
Contact: David M Notrica, MD    602-933-4144    dnotrica@surgery4children.com   
Contact: Crystal Langlais, MPH    602-933-5542    clanglais@phoenixchildrens.com   
Principal Investigator: David M Notrica, MD         
United States, Texas
John Sealy Hospital I The University of Texas Medical Branch Not yet recruiting
Galveston, Texas, United States, 77555
Contact: Ravi Radhakrishnan, MD    409-772-5666    rsradhak@utmb.edu   
Principal Investigator: Ravi Radhakrishnan, MD         
The University of Texas Health Science Center at Houston Recruiting
Houston, Texas, United States, 77030
Contact: Steven C Kosmach, MSN, RN, CCRC    713-500-7329    steven.kosmach@uth.tmc.edu   
Contact: Charles S Cox, Jr., M.D.       charles.s.cox@uth.tmc.edu   
Principal Investigator: Charles S. Cox, Jr., M.D.         
Sponsors and Collaborators
The University of Texas Health Science Center, Houston
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
Principal Investigator: Charles S Cox, Jr., M.D. The University of Texas Health Science Center, Houston
  More Information

Responsible Party: Charles Cox, Professor, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier: NCT01851083     History of Changes
Other Study ID Numbers: HSC-13-0038  R01NS077963 
Study First Received: May 5, 2013
Last Updated: April 20, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by The University of Texas Health Science Center, Houston:
Traumatic Brain Injury
TBI
pediatric
acute
stem cells

Additional relevant MeSH terms:
Brain Injuries
Brain Diseases
Central Nervous System Diseases
Craniocerebral Trauma
Nervous System Diseases
Trauma, Nervous System
Wounds and Injuries

ClinicalTrials.gov processed this record on May 04, 2016