NCT02231242

Brief Summary

The purpose of this study is to determine whether the infusion of intrathecal autologous bone marrow total nucleated cells would improve the neurologic evolution of pediatric patients with quadriparetic cerebral palsy.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
60

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Sep 2013

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2013

Completed
11 months until next milestone

First Submitted

Initial submission to the registry

July 14, 2014

Completed
2 months until next milestone

First Posted

Study publicly available on registry

September 4, 2014

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2015

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2016

Completed
Last Updated

September 4, 2014

Status Verified

September 1, 2014

Enrollment Period

2.2 years

First QC Date

July 14, 2014

Last Update Submit

September 3, 2014

Conditions

Cerebral Palsy

Keywords

brainchildrencerebral palsybone marrow stem cellsintrathecal autologous total nucleated cellsquadriparesis

Outcome Measures

Primary Outcomes (1)

  • Number of participants who show progress in GMFCS scale after autologous bonemarrow TNC intrathecal infusion.

    Patients, in an outpatient basis, will be stimulated with Granulocyte Colony Stimulating Factor (G-CSF) for 3 consecutive days. Their bone marrow will be harvested under sedation and, after being processed in the laboratory, the buffy coat of 10 mL will be infused intrathecally. Patient will be monitored during acute phase to register any adverse effect (malaise, headache, fever, and nausea or vomit, etc).Gross Motor Function Classification System (GMFCS) scale is going to be monitored at baseline, one, three and six months to measured differences between the scales. GMFCS is based on patient's self-initiated movement with particular emphasis on sitting, walking, and wheeled mobility. Distinctions between levels are based on functional abilities, the need for assistive technology, including hand-held mobility devices (walkers, crutches, or canes) or wheeled mobility, and to a much lesser extent, quality of movement.

    six months

Study Arms (2)

Intrathecal Autologous Bone Marrow TNC

EXPERIMENTAL

Procedure/Surgery: Intrathecal Autologous Bone Marrow TNC. Other Names: Autologous Stem Cell Transplantation Patients will be stimulated with Granulocyte Colony Stimulating Factor (G-CSF) (10mcgr/kg of body weight) for 3 consecutive days. Bone marrow will be harvested under sedation and, after being processed in the laboratory, the autologous TNC concentrate of 10 mL will be infused intrathecally.

Biological: Autologous Stem Cell Transplantation

Control group

NO INTERVENTION

Patients will be evaluated with the "Gross Motor Functional Classification System" initially, at one, three and six months, and then cross to the intervention arm.

Interventions

Autologous Stem Cell TransplantationBIOLOGICAL

Patients will be stimulated with Granulocyte Colony Stimulating Factor (G-CSF) 3 consecutive days. Bone marrow will be harvested under sedation and, after being processed in the laboratory, the buffy coat (TNC) of 10 mL will be infused intrathecally. Intrathecal Autologous Bone Marrow TNC

Intrathecal Autologous Bone Marrow TNC

Eligibility Criteria

Age7 Years - 9 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Patients with quadriplegic cerebral palsy, with an age from 7 to 9 years of age, regardless the age at the time of injury, time post-injury, or previously received therapies, different from ours

You may not qualify if:

  • Patients with neurodegenerative or autoimmune diseases
  • Patients with active infection in any organ or tissue at the time of entering the study, the onset of stimulation with G-CSF or at the procedure
  • Patients who do not sign the informed consent form

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hematology Service, Hospital Universitario Dr. Jose E. Gonzalez

Monterrey, Nuevo León, 64460, Mexico

RECRUITING

Related Publications (21)

  • Mancias-Guerra C, Marroquin-Escamilla AR, Gonzalez-Llano O, Villarreal-Martinez L, Jaime-Perez JC, Garcia-Rodriguez F, Valdes-Burnes SL, Rodriguez-Romo LN, Barrera-Morales DC, Sanchez-Hernandez JJ, Cantu-Rodriguez OG, Gutierrez-Aguirre CH, Gomez-De Leon A, Elizondo-Riojas G, Salazar-Riojas R, Gomez-Almaguer D. Safety and tolerability of intrathecal delivery of autologous bone marrow nucleated cells in children with cerebral palsy: an open-label phase I trial. Cytotherapy. 2014 Jun;16(6):810-20. doi: 10.1016/j.jcyt.2014.01.008. Epub 2014 Mar 15.

    PMID: 24642016BACKGROUND

  • Mehta T, Feroz A, Thakkar U, Vanikar A, Shah V, Trivedi H. Subarachnoid placement of stem cells in neurological disorders. Transplant Proc. 2008 May;40(4):1145-7. doi: 10.1016/j.transproceed.2008.03.026.

    PMID: 18555135BACKGROUND

  • Pakula AT, Van Naarden Braun K, Yeargin-Allsopp M. Cerebral palsy: classification and epidemiology. Phys Med Rehabil Clin N Am. 2009 Aug;20(3):425-52. doi: 10.1016/j.pmr.2009.06.001.

    PMID: 19643346BACKGROUND

  • Felling RJ, Snyder MJ, Romanko MJ, Rothstein RP, Ziegler AN, Yang Z, Givogri MI, Bongarzone ER, Levison SW. Neural stem/progenitor cells participate in the regenerative response to perinatal hypoxia/ischemia. J Neurosci. 2006 Apr 19;26(16):4359-69. doi: 10.1523/JNEUROSCI.1898-05.2006.

    PMID: 16624956BACKGROUND

  • Eglitis MA, Mezey E. Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):4080-5. doi: 10.1073/pnas.94.8.4080.

    PMID: 9108108BACKGROUND

  • Woodbury D, Schwarz EJ, Prockop DJ, Black IB. Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res. 2000 Aug 15;61(4):364-70. doi: 10.1002/1097-4547(20000815)61:43.0.CO;2-C.

    PMID: 10931522BACKGROUND

  • Mezey E, Key S, Vogelsang G, Szalayova I, Lange GD, Crain B. Transplanted bone marrow generates new neurons in human brains. Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1364-9. doi: 10.1073/pnas.0336479100. Epub 2003 Jan 21.

    PMID: 12538864BACKGROUND

  • Hayashi T, Iwai M, Ikeda T, Jin G, Deguchi K, Nagotani S, Zhang H, Sehara Y, Nagano I, Shoji M, Ikenoue T, Abe K. Neural precursor cells division and migration in neonatal rat brain after ischemic/hypoxic injury. Brain Res. 2005 Mar 15;1038(1):41-9. doi: 10.1016/j.brainres.2004.12.048.

    PMID: 15748871BACKGROUND

  • Nakatomi H, Kuriu T, Okabe S, Yamamoto S, Hatano O, Kawahara N, Tamura A, Kirino T, Nakafuku M. Regeneration of hippocampal pyramidal neurons after ischemic brain injury by recruitment of endogenous neural progenitors. Cell. 2002 Aug 23;110(4):429-41. doi: 10.1016/s0092-8674(02)00862-0.

    PMID: 12202033BACKGROUND

  • Rempe DA, Kent TA. Using bone marrow stromal cells for treatment of stroke. Neurology. 2002 Aug 27;59(4):486-7. doi: 10.1212/wnl.59.4.486. No abstract available.

    PMID: 12196638BACKGROUND

  • Li Y, Chen J, Chen XG, Wang L, Gautam SC, Xu YX, Katakowski M, Zhang LJ, Lu M, Janakiraman N, Chopp M. Human marrow stromal cell therapy for stroke in rat: neurotrophins and functional recovery. Neurology. 2002 Aug 27;59(4):514-23. doi: 10.1212/wnl.59.4.514.

    PMID: 12196642BACKGROUND

  • Gordon PH, Yu Q, Qualls C, Winfield H, Dillon S, Greene PE, Fahn S, Breeze RE, Freed CR, Pullman SL. Reaction time and movement time after embryonic cell implantation in Parkinson disease. Arch Neurol. 2004 Jun;61(6):858-61. doi: 10.1001/archneur.61.6.858.

    PMID: 15210522BACKGROUND

  • Kulbatski I, Mothe AJ, Nomura H, Tator CH. Endogenous and exogenous CNS derived stem/progenitor cell approaches for neurotrauma. Curr Drug Targets. 2005 Feb;6(1):111-26. doi: 10.2174/1389450053345037.

    PMID: 15720218BACKGROUND

  • Back SA, Rivkees SA. Emerging concepts in periventricular white matter injury. Semin Perinatol. 2004 Dec;28(6):405-14. doi: 10.1053/j.semperi.2004.10.010.

    PMID: 15693397BACKGROUND

  • Follett PL, Deng W, Dai W, Talos DM, Massillon LJ, Rosenberg PA, Volpe JJ, Jensen FE. Glutamate receptor-mediated oligodendrocyte toxicity in periventricular leukomalacia: a protective role for topiramate. J Neurosci. 2004 May 5;24(18):4412-20. doi: 10.1523/JNEUROSCI.0477-04.2004.

    PMID: 15128855BACKGROUND

  • Levison SW, Rothstein RP, Romanko MJ, Snyder MJ, Meyers RL, Vannucci SJ. Hypoxia/ischemia depletes the rat perinatal subventricular zone of oligodendrocyte progenitors and neural stem cells. Dev Neurosci. 2001;23(3):234-47. doi: 10.1159/000046149.

    PMID: 11598326BACKGROUND

  • Robinson S, Petelenz K, Li Q, Cohen ML, Dechant A, Tabrizi N, Bucek M, Lust D, Miller RH. Developmental changes induced by graded prenatal systemic hypoxic-ischemic insults in rats. Neurobiol Dis. 2005 Apr;18(3):568-81. doi: 10.1016/j.nbd.2004.10.024.

    PMID: 15755683BACKGROUND

  • Goldman SA, Schanz S, Windrem MS. Stem cell-based strategies for treating pediatric disorders of myelin. Hum Mol Genet. 2008 Apr 15;17(R1):R76-83. doi: 10.1093/hmg/ddn052.

    PMID: 18632701BACKGROUND

  • Herzog EL, Chai L, Krause DS. Plasticity of marrow-derived stem cells. Blood. 2003 Nov 15;102(10):3483-93. doi: 10.1182/blood-2003-05-1664. Epub 2003 Jul 31.

    PMID: 12893756BACKGROUND

  • Goodell MA. Stem-cell "plasticity": befuddled by the muddle. Curr Opin Hematol. 2003 May;10(3):208-13. doi: 10.1097/00062752-200305000-00003.

    PMID: 12690288BACKGROUND

  • Appel SH, Engelhardt JI, Henkel JS, Siklos L, Beers DR, Yen AA, Simpson EP, Luo Y, Carrum G, Heslop HE, Brenner MK, Popat U. Hematopoietic stem cell transplantation in patients with sporadic amyotrophic lateral sclerosis. Neurology. 2008 Oct 21;71(17):1326-34. doi: 10.1212/01.wnl.0000327668.43541.22.

    PMID: 18936424BACKGROUND

Related Links

MeSH Terms

Conditions

Cerebral PalsyQuadriplegia

Condition Hierarchy (Ancestors)

Brain Damage, ChronicBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesParalysisNeurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and Symptoms

Study Officials

  • Consuelo Mancias-Guerra, MD

    Hospital Universitario Dr. Jose E. Gonzalez

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Consuelo Mancias-Guerra, MD

CONTACT

+52 81 83 48 61 36consuelomanciasg@gmail.com

Oscar Gonzalez-Llano, MD

CONTACT

+52 86 75 67 18ogzzll25@hotmail.com

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
SUPPORTIVE CARE
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Dra. Consuelo Mancias Guerra

Study Record Dates

First Submitted

July 14, 2014

First Posted

September 4, 2014

Study Start

September 1, 2013

Primary Completion

December 1, 2015

Study Completion

June 1, 2016

Last Updated

September 4, 2014

Record last verified: 2014-09

Locations

ME(1)