Mesenchymal Stem Cells for the Treatment of MS

• ClinicalTrials.gov Identifier: NCT00781872
• Recruitment Status: Completed
• First Posted: October 29, 2008
• Last Update Posted: June 13, 2019
• Sponsor: Hadassah Medical Organization
• Information provided by (Responsible Party): Dimitrios Karussis, Hadassah Medical Organization

Tracking Information

• First Submitted Date: October 28, 2008
• First Posted Date: October 29, 2008
• Last Update Posted Date: June 13, 2019
• Actual Study Start Date: October 2006
• Actual Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 28, 2008): safety and migration ability of the injected cells [ Time Frame: one year ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: October 28, 2008): clinical efficacy in disability score [ Time Frame: one year ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Mesenchymal Stem Cells for the Treatment of MS
• 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)

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: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Multiple Sclerosis

Intervention

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 28, 2008): 20
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: December 2009
• Actual Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 35 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT00781872
• Other Study ID Numbers: MS22MSC-HMO-CTIL
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Dimitrios Karussis, Hadassah Medical Organization
• Study Sponsor: Hadassah Medical Organization
• Collaborators: Not Provided

Investigators

• Principal Investigator: Dimitrios Karussis, Prof.; Hadassah Medical Organization

• PRS Account: Hadassah Medical Organization
• Verification Date: June 2019