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Mesenchymal Stem Cells for the Treatment of MS

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified October 2008 by Hadassah Medical Organization.
Recruitment status was:  Active, not recruiting
Sponsor:
ClinicalTrials.gov Identifier:
NCT00781872
First Posted: October 29, 2008
Last Update Posted: October 29, 2008
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by:
Hadassah Medical Organization
  Purpose

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.


Condition Intervention Phase
Multiple Sclerosis Biological: injection of autologous stem cells Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Hadassah Medical Organization:

Primary Outcome Measures:
  • safety and migration ability of the injected cells [ Time Frame: one year ]

Secondary Outcome Measures:
  • clinical efficacy in disability score [ Time Frame: one year ]

Enrollment: 20
Study Start Date: October 2006
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: open
a group of patients with active multiple sclerosis, failures to respond to other treatments
Biological: injection of autologous stem cells
60 milion cells intrathecally and 20 milion intravenously
Other Name: stromal cells of bone marrow

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   35 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Consenting patients fulfilling the Poser's clinical criteria for definite MS
  2. Age: 35-65, males and females
  3. Duration of disease: >5 years
  4. 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

  1. Patients who were treated with cytotoxic medications (cyclophosphamide, Mitoxanthrobne etc) during the last 3 months prior to the inclusion
  2. 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
  3. Patients with active infections
  4. Patients with severe cognitive decline or inability to understand and sign the informed consent
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00781872


Sponsors and Collaborators
Hadassah Medical Organization
Investigators
Principal Investigator: Dimitrios Karussis, Prof. Hadassah Medical Organization
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: PROF. DIMITRIOS KARUSSIS, HADASSAH MEDICAL ORGANIZATION
ClinicalTrials.gov Identifier: NCT00781872     History of Changes
Other Study ID Numbers: MS22MSC-HMO-CTIL
First Submitted: October 28, 2008
First Posted: October 29, 2008
Last Update Posted: October 29, 2008
Last Verified: October 2008

Keywords provided by Hadassah Medical Organization:
multiple sclerosis (MS)
bone marrow stromal cells
stem cells

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases