Mesenchymal Stem Cells for the Treatment of MS

Tracking Information
First Submitted Date ICMJE	October 28, 2008
First Posted Date ICMJE	October 29, 2008
Last Update Posted Date	October 29, 2008
Study Start Date ICMJE	October 2006
Estimated Primary Completion Date	December 2009 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: October 28, 2008)	safety and migration ability of the injected cells [ Time Frame: one year ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	No Changes Posted
Current Secondary Outcome Measures ICMJE; (submitted: October 28, 2008)	clinical efficacy in disability score [ Time Frame: one year ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Mesenchymal Stem Cells for the Treatment of MS
Official Title ICMJE	Explorative Trial to Investigate the Migration Ability of Mesenchymal Bone Marrow Stem Cells (MSC) in the Central Nervous System (CNS) Following Their Intrathecal Administration in Severe Cases of Multiple Sclerosis (MS)
Brief Summary	Multiple sclerosis is a multifocal inflammatory disease of the central nervous system which affects young individuals and causes paralysis of the limbs, sensation, visual and sphincter problems. The disease is caused by an autoimmune mechanism, ie the immune system produces antibodies and cells which attack the self myelin antigens, causing therefore demyelination. The disease is clinically evident with relapses of neurological disability due to the dysfunction of the areas (plaques of multiple sclerosis) in which damage of myelin occurs. Disability can accumulate with time and the disease enters a progressive phase due to damage of the axons and irreversible neurodegeneration. Although, effective immunotherapies exist which downregulate the autoimmune anti-myelin reactivity and reduce the rate of relapses of MS (like Copaxone and interferons), there is no effective means today to stop the progression of disability and induce rebuilding of the destroyed myelin (re-myelination). Neuronal stem cells were shown to possess the ability to restore neuronal activity and produce new neurons through transdifferentiation. Various other types of stem cells were tested in animal models with promising results, revealing a potential for restoration of the neurological function in neuroimmune and neurodegenerative conditions and in central nervous system traumatic injury. Adult bone marrow derived stromal cells (MSC) were shown to induce similar (to the neuronal stem cells) immunomodulatory and neuroregenerative effects and were shown in our laboratory to induce neuroprotection in the animal model of chronic experimental autoimmune encephalomyelitis (EAE). These bone marrow derived MSCs offer practical advantages for clinical therapeutic applications, since they can be obtained from the adult bone marrow and therefore the patient can be the donor for himself, without any danger for rejection of the cells. In addition, MSCs carry a safer profile and are less prone to malignant transformation. Our initial clinical experience with 10 patients with ALS and 10 with multiple sclerosis show that intravenous and intrathecal administration of MSCs is feasible and safe. In this study we propose an explorative protocol with the injection of MSCs (both intrathecally and intravenously) in patients with MS, in an effort to prevent further neurodegeneration through neuroprotective mechanisms and induce neuroregeneration and restoration of neuronal function. This will be a phase I/II study. The primary endpoint will be to further evaluate the safety and feasibility of the treatment with MSC infusions, in MS patients. Additionally, the migration ability of the transplanted cells will be evaluated by tagging MSCs with the superparamagnetic iron oxide particle (Feridex) (an FDA approved cell tracking drug) for detection by MRI. MRI of the brain and spinal cord will be performed at weeks 1, 4, 12 and 24 to detect the migration of the stem cells. Clinically the patients will be followed by monthly evaluations of the MS functional rating scale (EDSS) scale. The MRI, will be also used to evaluate changes in the total volume of lesions in the brain and the degree of atrophy. Significance: Our center has performed the first clinical trial with intrathecal and intravenous injection of adult stem cells in MS and ALS patients and has gained experience during the last 3 years with this type of stem cells treatment. After having evaluated the safety and feasibility issues, we intent to proceed to the second stage, to evaluate the migration ability of those cells (their ability to reach the affected motor areas of the CNS gray matter, by tracking them with a paramagnetic material and visualize them by MRI), and evaluate indications of clinical efficacy. This project may provide information for possible therapeutic uses of this type of bone marrow adult stem cells in MS and ALS but may also serve as a pilot platform and pave the path for future applications of various types of stem cells in neurodegerative diseases in general.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 1; Phase 2
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Multiple Sclerosis
Intervention ICMJE	Biological: injection of autologous stem cells; 60 milion cells intrathecally and 20 milion intravenously; Other Name: stromal cells of bone marrow
Study Arms	Experimental: open; a group of patients with active multiple sclerosis, failures to respond to other treatments; Intervention: Biological: injection of autologous stem cells
Publications *	Karussis D, Karageorgiou C, Vaknin-Dembinsky A, Gowda-Kurkalli B, Gomori JM, Kassis I, Bulte JW, Petrou P, Ben-Hur T, Abramsky O, Slavin S. Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Arch Neurol. 2010 Oct;67(10):1187-94. doi: 10.1001/archneurol.2010.248.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Unknown status
Actual Enrollment ICMJE; (submitted: October 28, 2008)	20
Original Actual Enrollment ICMJE	Same as current
Study Completion Date	Not Provided
Estimated Primary Completion Date	December 2009 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Consenting patients fulfilling the Poser's clinical criteria for definite MS; Age: 35-65, males and females; Duration of disease: >5 years; Failure to the currently available -registered- for MS immunomodulatory treatments (ie interferons, Copaxone, immunosuppression): the lack of response to (at least two) of these treatments will be determined/defined by either an increase (deterioration) of at least one degree in the EDSS score during the last year or the appearance of at least two major relapses of MS during the same period of time (under treatment). Exclusion criteria; Patients who were treated with cytotoxic medications (cyclophosphamide, Mitoxanthrobne etc) during the last 3 months prior to the inclusion; Patients suffering from significant cardiac, renal or hepatic failure or any other disease that may risk the patient or interfere with the ability to interpret the results; Patients with active infections; Patients with severe cognitive decline or inability to understand and sign the informed consent
Sex/Gender	Sexes Eligible for Study: All
Ages	35 Years to 65 Years (Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Not Provided
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00781872
Other Study ID Numbers ICMJE	MS22MSC-HMO-CTIL
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	PROF. DIMITRIOS KARUSSIS, HADASSAH MEDICAL ORGANIZATION
Study Sponsor ICMJE	Hadassah Medical Organization
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Dimitrios Karussis, Prof. Hadassah Medical Organization
PRS Account	Hadassah Medical Organization
Verification Date	October 2008
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP