Intrathecal Stem Cells for Cerebral Palsy Phase II

Cerebral Palsy Clinical Trial

— ISCII  

Official title:

Intrathecal Autologous Stem Cells for Children With Cerebral Palsy Phase II

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02231242
• Other study ID #: HE13-004
• Status: Recruiting
• Phase: Phase 2
• First received: July 14, 2014
• Last updated: September 3, 2014
• Start date: September 2013
• Est. completion date: June 2016

Study information

• Verified date: September 2014
• Source: Hospital Universitario Dr. Jose E. Gonzalez
• Contact: Consuelo Mancias-Guerra, MD
• Phone: +52 81 83 48 61 36
• Email: consuelomanciasg[@]gmail.com
• Is FDA regulated: No
• Health authority: Mexico: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Description:

There is accumulated evidence that shows that the administration of bone marrow total nucleated cells (TNC) into the brain may produce some benefits by different mechanisms like cytokine production, in several neurological areas such as motor, social, adaptative and cognitive.

It has been found that after introducing TNC in the subarachnoid space of the spinal cord, these cells may be transported through the cerebrospinal fluid and can be delivered more efficiently to the injured area, compared with intravenous route in patients with neurologic injury.

Patients will be stimulated for 3 consecutive days with subcutaneous granulocyte colony stimulating factor (G-CSF) and then their bone marrow will be harvested according to their weight. Bone marrow will be processed in order to obtain the buffy coat and minimize the amount of red blood cells. An inoculum of 10mL of this TNC will be infused intrathecally. Patients will be evaluated with the "Gross Motor Functional Classification System" before the procedure and one, three and six months after that.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: June 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 7 Years to 9 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Cerebral Palsy

Intervention

Biological:
• Autologous Stem Cell Transplantation
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

Locations

Country	Name	City	State
Mexico	Hematology Service, Hospital Universitario Dr. Jose E. Gonzalez	Monterrey	Nuevo Leon

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Universitario Dr. Jose E. Gonzalez

Country where clinical trial is conducted

Mexico, 

References & Publications (21)

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. — View Citation

Back SA, Rivkees SA. Emerging concepts in periventricular white matter injury. Semin Perinatol. 2004 Dec;28(6):405-14. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

Goodell MA. Stem-cell "plasticity": befuddled by the muddle. Curr Opin Hematol. 2003 May;10(3):208-13. Review. — View Citation

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. — View Citation

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. — View Citation

Herzog EL, Chai L, Krause DS. Plasticity of marrow-derived stem cells. Blood. 2003 Nov 15;102(10):3483-93. Epub 2003 Jul 31. Review. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

Mancías-Guerra C, Marroquín-Escamilla AR, González-Llano O, Villarreal-Martínez L, Jaime-Pérez JC, García-Rodríguez F, Valdés-Burnes SL, Rodríguez-Romo LN, Barrera-Morales DC, Sánchez-Hernández JJ, Cantú-Rodríguez OG, Gutiérrez-Aguirre CH, Gómez-De León A, Elizondo-Riojas G, Salazar-Riojas R, Gómez-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. — View Citation

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. — View Citation

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. Epub 2003 Jan 21. — View Citation

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. — View Citation

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. Review. — View Citation

Rempe DA, Kent TA. Using bone marrow stromal cells for treatment of stroke. Neurology. 2002 Aug 27;59(4):486-7. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No

External Links

•   web page