Pediatric Autologous Bone Marrow Mononuclear Cells for Severe Traumatic Brain Injury

NCT01851083 | Completed Phase 2 DMC

• 2 other identifiers: HSC-MS-13-0038R01NS077963
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 2

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.

Conditions

Traumatic Brain Injury

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  one year post infusion

Other Outcomes (1)

• Infusional toxicity safety evaluations

  7 days post-infusion

Study Arms (2)

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.

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.

Other: Placebo Infusion

Interventions

autologous bone marrow mononuclear cells BIOLOGICAL

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

Also known as: BMMNCs

autologous bone marrow mononuclear cells

Placebo Infusion OTHER

Placebo infusion of 0.9% Sodium Chloride

Also known as: Saline Infusion

placebo infusion

Eligibility Criteria

• Age: 5 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (2)

Phoenix Children's Hospital I University of Arizona

Phoenix, Arizona, 85006, United States

Location

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Brain Injuries, Traumatic

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Study Officials

• Charles S Cox, Jr., M.D.

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 5, 2013
• First Posted: May 10, 2013
• Study Start: August 1, 2013
• Primary Completion: September 16, 2020
• Study Completion: October 12, 2020
• Last Updated: November 20, 2020

Record last verified: 2020-11

Locations

US (2)