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)

Patrocinadores

Patrocinador principal: The University of Texas Health Science Center, Houston

Colaborador: National Institute of Neurological Disorders and Stroke (NINDS)

Fuente The University of Texas Health Science Center, Houston
Resumen breve

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.

Descripción detallada

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.

Estado general Active, not recruiting
Fecha de inicio August 2013
Fecha de Terminación August 2020
Fecha de finalización primaria July 2020
Fase Phase 1/Phase 2
Tipo de estudio Interventional
Resultado primario
Medida Periodo de tiempo
brain white matter and gray matter structural preservation on diffusion tensor magnetic resonance imaging (DTMRI) one year post infusion
Resultado secundario
Medida Periodo de tiempo
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
Inscripción 47
Condición
Intervención

Tipo de intervención: Biological

Nombre de intervención: autologous bone marrow mononuclear cells

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

Etiqueta de grupo de brazo: autologous bone marrow mononuclear cells

Otro nombre: BMMNCs

Tipo de intervención: Other

Nombre de intervención: Placebo Infusion

Descripción: Placebo infusion of 0.9% Sodium Chloride

Etiqueta de grupo de brazo: placebo infusion

Otro nombre: Saline Infusion

Elegibilidad

Criterios:

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.

Género: All

Edad mínima: 5 Years

Edad máxima: 17 Years

Voluntarios Saludables: No

Oficial general
Apellido Papel Afiliación
Charles S Cox, Jr., M.D. Principal Investigator The University of Texas Health Science Center, Houston
Ubicación
Instalaciones:
Phoenix Children's Hospital I University of Arizona | Phoenix, Arizona, 85006, United States
The University of Texas Health Science Center at Houston | Houston, Texas, 77030, United States
Ubicacion Paises

United States

Fecha de verificación

May 2020

Fiesta responsable

Tipo: Principal Investigator

Afiliación del investigador: The University of Texas Health Science Center, Houston

Nombre completo del investigador: Charles Cox

Título del investigador: Professor

Palabras clave
Tiene acceso ampliado No
Condición Examinar
Número de brazos 2
Grupo de brazo

Etiqueta: autologous bone marrow mononuclear cells

Tipo: Experimental

Descripción: a bone marrow harvest will be performed, followed by a single intravenous infusion of autologous bone marrow mononuclear cells within 48 hours of injury.

Etiqueta: placebo infusion

Tipo: Placebo Comparator

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

Información de diseño del estudio

Asignación: Randomized

Modelo de intervención: Parallel Assignment

Propósito primario: Treatment

Enmascaramiento: Triple (Participant, Care Provider, Outcomes Assessor)

Fuente: ClinicalTrials.gov