Autologous Stem Cell Study for Adult TBI (Phase 2b)

NCT02525432 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: HSC-MS-16-0283
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the effect of intravenous infusion of autologous bone marrow mononuclear cells (BMMNC) on brain structure and neurocognitive/functional outcomes after severe traumatic brain (TBI) injury in adults. The primary objective is to determine if the intravenous infusion of autologous BMMNC after severe TBI results in structural preservation of global gray matter (GM) volume and white matter (WM) volume and integrity; as well as select regions of interest in the corpus callosum. THe secondary objectives are to determine if autologous BMMNC infusion improves functional and neurocognitive deficits in adults after TBI; reduces the neuroinflammatory response to TBI; evaluate spleen size and splenic blood flow over time using ultrasound and corresponding changes in inflammatory cytokines; and infusion related toxicity and long-term follow-up safety evaluations.

Conditions

Brain Injuries, Traumatic; Brain Injuries, Acute; TBI (Traumatic Brain Injury)

Keywords

Mesenchymal Stromal Cells, Multipotent; Multipotent Mesenchymal Stromal Cells; Stem Cells, Mesenchymal

Outcome Measures

Primary Outcomes (1)

• Macro and micro structural properties of grey matter (GM) and white matter (WM) regions will measured using high-resolution anatomical MRI and diffusion tensorm imaging and comparisons made between groups.

  Subjects will undergo three 3T-MRI evaluations. The first will occur 7 to 10 days after hospitalization, when clinically stable. The following five pulse sequences constitute a complete imaging session: 1) conventional localizer/scout 2) 3D isotropic T1-weighted MPRAGE 3) 3D isotropic T2-weighted TSE 4) 32-direction single-shot spin-echo diffusion sensitized echo-planar (DTI-32dir) 5) 3D-FLAIR. The 3T-MRI will be repeated at 1 and 6 months post-injury. Composite scores will be calculated for comparison.

  up to 6 months. Post Head Injury

Secondary Outcomes (7)

• Brain imaging measures of GM and WM structural integrity will be compared to functional and neurocognitive scores and comparisons made between groups.

  Changes From Baseline to 6 mo. Post Head Injury

• Compare neuro-inflammatory biomarkers between groups..

  Changes From Baseline to 6 mo. Post Head Injury

• Measure the number of participants with infusion related adverse events.

  up to 6 mo. Post Head Injury

• Measure spleen ultrasound size over time and corresponding changes in inflammatory cytokines.

  up to 6 mo. Post Head Injury

• Determine if microglial activation is associated with TBI and can be accurately measured with brain PET and DT-MRI imaging when compared to PET imaging data from healthy volunteers (enrolled under a different protocol).

  1 yr. Post Head Injury

Study Arms (2)

Autologous BMMNC Infusion

EXPERIMENTAL

Subjects randomized to the treatment group will undergo a bone marrow harvest and then receive an autologous infusion of BMMNC's starting with the lowest dose (6 x 10\^6 cells/kg body weight) and progressing to the high dose of 9 x 10\^6 cells/kg body weight using a Bayesian adaptive dose escalation design.

Biological: Autologous BMMNC Infusion

Placebo Infusion

PLACEBO COMPARATOR

Subjects randomized to the placebo control group will undergo a "sham" bone marrow harvest.

Biological: Placebo Infusion

Interventions

Placebo Infusion BIOLOGICAL

In addition to the standard of care provided to all patients with traumatic brain injury, subjects assigned to the placebo control group will undergo a sham bone marrow harvest and receive a placebo infusion of saline.

Placebo Infusion

Autologous BMMNC Infusion BIOLOGICAL

In addition to the standard of care provided to all patients with traumatic brain injury, subjects assigned to the BMMNC treatment group will undergo a bone marrow harvest and then receive an autologous stem cell infusion.

Also known as: Stem Cell Infusion

Autologous BMMNC Infusion

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Adults 18 to 55 years of age on the day of injury,
• Non-penetrating closed head trauma.
• Glasgow Coma Score between (GCS) between 3 and 8, (best un-medicated post-resuscitation score during screening).
• Ability to obtain legally authorized representative consent for participation 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:

• Known history of:
• previous brain injury,
• intellectual deficiency or psychiatric condition likely to invalidate our ability to assess post-injury changes in cognition or behavior,
• neurologic impairment and/or deficit,
• seizure disorder requiring anti-convulsant therapy,
• recently treated significant infection,
• renal disease/altered renal function (post-resuscitation serum creatinine \> 1.5 mg/dL),
• chronic hepatic disease or altered liver function (post-resuscitation SGPT \> 150 U/L, and/or T. Bilirubin \>1.3 mg/dL),
• cancer,
• Chemical or ETOH dependency,
• immunosuppression (admission WBC \< 3X103),
• HIV positive status;
• Obliteration of perimesencephalic cistern on initial head CT/MRI suggesting prolonged hypoxic ischemic insult;
• Initial hospital ICP \> 40 mm Hg;
• Hemodynamic instability at the time of screening defined as SBP \< 90mmHg, ongoing fluid resuscitation and/or requirement for inotropic support to maintain MAP at or above normals for age - does not include CPP based inotropic support;

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead
• United States Department of Defense: collaborator
• U.S. Army Medical Research and Development Command: collaborator

Study Sites (1)

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Brain Injuries, Traumatic; Brain Injuries

Condition Hierarchy (Ancestors)

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

Study Officials

• Charles S Cox, MD

  UTHealth McGovern Medical School, Houston, TX

  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, Department of Pediatric Surgery

Study Record Dates

• First Submitted: March 23, 2015
• First Posted: August 17, 2015
• Study Start: November 21, 2016
• Primary Completion: July 1, 2024
• Study Completion: January 1, 2025
• Last Updated: May 9, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)