Pediatric Autologous Bone Marrow Mononuclear Cells for Severe Traumatic Brain Injury

NCT ID: NCT01851083

Last Updated: 2020-11-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2020-10-12

Brief 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. 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.

Conditions

Traumatic Brain Injury

Keywords

Traumatic Brain Injury; TBI; pediatric; acute; stem cells

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

autologous bone marrow mononuclear cells

Intervention Type: BIOLOGICAL

BMMNC infusion of either 6x10\^6 cells/kg or 10x10\^6 cells/kg weight.

placebo infusion

a sham harvest will be performed, followed by a single intravenous placebo infusion within 48 hours of injury.

Group Type: PLACEBO_COMPARATOR

Placebo Infusion

Intervention Type: OTHER

Placebo infusion of 0.9% Sodium Chloride

Interventions

autologous bone marrow mononuclear cells

BMMNC infusion of either 6x10\^6 cells/kg or 10x10\^6 cells/kg weight.

Intervention Type: BIOLOGICAL

Placebo Infusion

Placebo infusion of 0.9% Sodium Chloride

Intervention Type: OTHER

Other Intervention Names

BMMNCs; Saline Infusion

Eligibility 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 pregnancy test, if applicable.

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.

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role: lead

Responsible Party

Charles Cox

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Charles S Cox, Jr., M.D.

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center, Houston

Locations

Phoenix Children's Hospital I University of Arizona

Phoenix, Arizona, United States

The University of Texas Health Science Center at Houston

Houston, Texas, United States

Countries

United States

Other Identifiers

R01NS077963

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HSC-MS-13-0038

Identifier Type: -

Identifier Source: org_study_id